Gene Detail

Gene Symbol TP53
Synonyms BCC7 | BMFS5 | LFS1 | P53 | TRP53
Gene Description TP53, cellular tumor antigen p53, is a tumor suppressor involved in cell cycle arrest and apoptosis, and is the most frequently mutated gene in cancer (PMID: 10065147, PMID: 22713868). TP53 germline mutations are common in Li-Fraumeni syndrome (PMID: 30239254) and somatic missense mutations are frequent in almost all cancer types cancers (PMID: 30224644) and are also implicated in chemoresistance (PMID: 9927204, PMID: 24065105, PMID: 27066457).
ACMG Incidental List v2.0:
Yes, Li-Fraumeni syndrome 1 (PMID: 27854360)
Entrez Id 7157
Chromosome 17
Map Location 17p13.1
Canonical Transcript NM_000546

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
L330H missense loss of function TP53 L330H lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). L330H results in decreased Tp53 tetramerization and transcriptional activity in cell culture (PMID: 19454241, PMID: 9766574).
N131T missense unknown TP53 N131T lies within the DNA binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). N131T has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
G266V missense unknown TP53 G266V lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G266V has been identified in sequencing studies (PMID: 21094160), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
D281A missense loss of function - predicted TP53 D281A lies within the DNA-binding region of the Tp53 protein (UniProt.org). D281A is predicted to confer a loss of function to the Tp53 protein, as demonstrated by impaired oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 18524770).
S121C missense gain of function - predicted TP53 S121C lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). S121C is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
C242fs frameshift loss of function - predicted TP53 C242fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 242 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the oligomerization domain (UniProt.org), C242fs is predicted to lead to a loss of Tp53 protein function.
R158C missense unknown TP53 R158C lies within the DNA-binding domain of the Tp53 protein (PMID: 21760703). R158C has been identified in the scientific literature (PMID: 25561229, PMID: 9185695), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
H193P missense loss of function TP53 H193P lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). H193P results in a loss of Tp53 transactivation activity and inability to suppress colony formation in cell culture (PMID: 25584008).
S240T missense unknown TP53 S240T lies within the DNA-binding domain and the HIPK1, ZNF385A and AXIN1-interacting region of the Tp53 protein (UniProt.org). S240T has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
F338Y missense unknown TP53 F338Y lies within the oligomerization and HIPK1, CARM1, HIPK2-interacting regions of the Tp53 protein (UniProt.org). F338Y has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
H179Q missense loss of function TP53 H179Q lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H179Q results in decreased Tp53 transactivation activity and disruption of the G1 checkpoint in cell culture (PMID: 16209708, PMID: 22540896).
N200K missense unknown TP53 N200K lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). N200K has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R213fs frameshift loss of function - predicted TP53 R213fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 213 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), R213fs is predicted to lead to a loss of Tp53 protein function.
E258Q missense loss of function TP53 E258Q lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). E258Q confers a loss of Tp53 DNA binding ability and transcriptional activation in cell culture (PMID: 21643018).
R342* nonsense unknown TP53 R342* results in a premature truncation of the Tp53 protein at amino acid 342 of 393 (UniProt.org). R342* has been identified in the scientific literature (PMID: 29085664, PMID: 29058986), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R273C missense loss of function TP53 R273C is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R273C results in decreased activation of wild-type Tp53 target genes, as well as aberrant activation of gene expression, and increased cell proliferation and migration in culture (PMID: 23264849, PMID: 23612969, PMID: 16861262).
V173L missense loss of function TP53 V173L lies within the DNA-binding domain of the Tp53 protein (PMID: 23246812). V173L results in aberrant Tp53 localization and decreased Tp53 target transactivation, and leads to increased cell growth and diminished Tp53 pro-apoptotic function in culture (PMID: 23246812).
G154V missense unknown TP53 G154V lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G154V results in decreased Tp53 transactivation activity (PMID: 8336941), and is therefore predicted to confer a loss of function to the Tp53 protein.
P98L missense unknown TP53 P98L lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). P98L has been identified in the scientific literature (PMID: 21118481), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2017).
D259V missense unknown TP53 D259V lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). D259V results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
G154R missense unknown TP53 G154R lies within the DNA-binding domain of the p53 protein (UniProt.org). G154R has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
Y234C missense loss of function TP53 Y234C lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). Y234C results in decreased Tp53 transactivation and interferes with wild-type Tp53 function in cell culture, and correlates with protein aggregates in human tumor samples (PMID: 21056685, PMID: 16861262).
S106T missense unknown TP53 S106T lies within the DNA-binding domain and the WWOX, HIPK1 and ZNF385A-interacting region of the Tp53 protein (UniProt.org). S106T has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
G245S missense loss of function TP53 G245S is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245S results in a loss of wild-type Tp53 transcriptional activity, and also confers a gain of function to Tp53, resulting in enhanced Akt signaling and transformation in cell culture (PMID: 20212049, PMID: 23538418, PMID: 17417775).
exon8 unknown unknown TP53 exon 8 indicates an unspecified mutation has occurred in exon 8 of the TP53 gene.
P309S missense unknown TP53 P309S lies within the CCAR2, HIPK1, and CARM1-interacting region of the Tp53 protein (UniProt.org). P309S results in constitutive activation of p21 in conjunction with P273H (PMID: 16061257), but has not been individually characterized and therefore, its effect on Tp53 protein function is unknown.
V272A missense unknown TP53 V272A lies within the DNA-binding domain and HIPK1, ZNF385A, AXIN1, and E4F1-interacting regions of the Tp53 protein (UniProt.org). V272A resulted in increased expression of p53 in an in-vitro assay (PMID: 28363997), but has not been otherwise characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P223R missense unknown TP53 P223R lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P223R has been identified in the scientific literature (PMID: 21197471, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2017).
G105D missense unknown TP53 G105D lies within the DNA binding domain of the Tp53 protein (UniProt.org). G105D has been identified in the scientific literature (PMID: 16000567, PMID: 27273737), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
G334R missense gain of function TP53 G334R lies within the hinge residue of the oligomerization domain of the Tp53 protein (PMID: 16007150). G334R results in increased Tp53 transactivation activity and suppression of colony formation in cell culture (PMID: 25584008).
G112D missense unknown TP53 G112D lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G112D has not been characterized in the scientific literature and therefore, its effect onTp53 protein function is unknown (PubMed, Oct 2018).
R335H missense unknown TP53 R335H lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). R335H has not been biochemically characterized, but results in increased monomer Tp53 compared to wild-type in cell culture (PMID: 19454241).
A307T missense unknown TP53 A307T lies within the CARM1-interacting region of the Tp53 protein (UniProt.org). A307T has been identified in sequencing studies (PMID: 28949453), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R213* missense loss of function - predicted TP53 R213* results in a premature truncation of the Tp53 protein at amino acid 213 of 393 (UniProt.org). Due to the loss of the much of the DNA binding domain, as well as the tetramerization domain and C-terminal basic domain, R213* is predicted to result in a loss of Tp53 protein function (PMID: 20978130).
H193Y missense unknown TP53 H193Y lies within the DNA binding domain of the Tp53 protein (UniProt.org). H193Y has been identified in sequencing studies (PMID: 27998224, PMID: 27659017), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Jul 2018).
H168D missense unknown TP53 H168D lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H168D has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R273W missense loss of function - predicted TP53 R273W is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R273W is predicted to confer a loss of function to the Tp53 protein as demonstrated by decreased gene transcription in response to Tgf-beta treatment in cell culture (PMID: 17875924).
F328S missense loss of function - predicted TP53 F328S lies within the HIPK1, CARM1 and HIPK2-interacting and oligomerization region of the Tp53 protein (UniProt.org). F328S has not been biochemically characterized in human cells, but results in decreased Tp53 transcriptional activity in yeast assays, and is predicted to decrease Tp53 stability in computational models (PMID: 16007150, PMID: 20978130).
A189T missense unknown TP53 A189T lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A189T has been identified in the scientific literature (PMID: 8688317), but has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S215T missense unknown TP53 S215T lies within the DNA-binding domain and HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). S215T has been demonstrated to result in increased Tp53 transcriptional activity in yeast (PMID: 11313981), but has not been biochemically characterized in human cells and therefore its effect on Tp53 protein function is unknown.
R181P missense loss of function - predicted TP53 R181P lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). R181P is predicted to confer a loss of function to the Tp53 protein, as demonstrated by in a loss of Tp53 transactivation activity in cell culture (PMID: 23149933).
T377P missense unknown TP53 T377P lies within the region of the Tp53 protein involved in repression of DNA binding and the CARM1-interacting region (UniProt.org). T377P has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
Y205C missense loss of function TP53 Y205C lies within the DNA binding domain of the Tp53 protein (UniProt.org). Y205C demonstrates decreased Tp53 transactivation activity in cultured cells (PMID: 15037740, PMID: 22710932).
T329A missense no effect TP53 T329A lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). T329A demonstrates activity similar to wild-type TP53 including transactivation activity, suppression of the MDR-1 promoter, and cell growth inhibition (PMID: 10329187).
L265V missense unknown TP53 L265V lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). L265V has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R175H missense loss of function TP53 R175H is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R175H results in decreased activation of Tp53 targets and interferes with activation by wild-type Tp53, leads to resistance to apoptosis, decreased genomic stability, and promotes tumorigenesis, and additionally confers a gain of function to Tp53, resulting in aberrant activation of gene transcription and enhanced cell migration (PMID: 10713666, PMID: 22114072, PMID: 19881536, PMID: 14743206).
T170M missense unknown TP53 T170M lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). T170M has been identified in the scientific literature (PMID: 21925707, PMID: 25480502, PMID: 28744014), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
V203E missense unknown TP53 V203E lies within the DNA-binding domain and the CCAR2, HIPK1, ZNF385A, FBXO42, and AXIN1-interacting regions of the Tp53 protein (UniProt.org). V203E has been identified in sequencing studies (PMID: 30309854, PMID: 24501221), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C229R missense unknown TP53 C229R lies within the DNA-binding domain of the Tp53 protein (UniProt.org). The functional effect of C229R is conflicting, as it has been demonstrated to result in decreased ability to suppress colony formation in cell culture, but increased Tp53 transactivation activity in one assay (PMID: 25584008), and decreased transactivation activity in another assay (PMID: 28369373).
V173A missense loss of function - predicted TP53 V173A lies within the DNA binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). V173A demonstrates reduced Tp53 transactivation activity in cell culture (PMID: 10617466), and therefore is predicted to confer a loss of function to the Tp53 protein.
I255del deletion unknown TP53 I255del results in the deletion of one amino acid in the DNA-binding domain of the Tp53 protein at amino acid 255 (PMID: 15510160). I255del has been identified in the scientific literature (PMID: 27998224, PMID: 27659017), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Jul 2018).
mutant unknown unknown TP53 mutant indicates an unspecified mutation within the TP53 gene.
R158P missense unknown TP53 R158P lies within the DNA binding domain of the Tp53 protein (PMID: 21760703). R158P results in decreased Tp53 transactivation activity in yeast (PMID: 16861262), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
T253I missense unknown TP53 T253I lies within the DNA-binding domain and the HIPK1, ZNF385A and AXIN1-interacting region of the Tp53 protein (UniProt.org). T253I has been identified in the scientific literature (PMID: 29979965), but has not been biochemicallly characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S96F missense unknown TP53 S96F lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S96F has been identified in the scientific literature (PMID: 15308588, PMID: 19336573), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S241F missense loss of function TP53 S241F lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). S241F results in a decreased in Tp53 transcriptional activity (PMID: 19225112, PMID: 26585234), and interferes with formation of the Tp53/Bard1/CstF complex in cell culture (PMID: 21383700).
N239T missense unknown TP53 N239T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). N239T results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
R209Kfs*6 frameshift loss of function - predicted TP53 R209Kfs*6 indicates a shift in the reading frame starting at amino acid 209 and terminating 6 residues downstream causing a premature truncation of the 393 amino acid Tp53 protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (UniProt.org, PMID: 21561095), R209Kfs*6 is predicted to lead to a loss of Tp53 protein function.
R175X missense loss of function - predicted TP53 R175X indicates a hotspot mutation resulting in an amino acid change at codon 175 of the Tp53 protein, which is predicted to result in a loss of Tp53 protein function.
N131K missense unknown TP53 N131K lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). N131K has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R196* nonsense loss of function - predicted TP53 R196* results in a premature truncation of the Tp53 protein at amino acid 196 of 393 (UniProt.org). Due to the loss of several functional domains (UniProt.org), R196* is predicted to lead to a loss of Tp53 protein function.
E294G missense unknown TP53 E294G lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). E294G has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
F212V missense unknown TP53 F212V lies within the DNA-binding domain of the Tp53 protein (UniProt.org). F212V has been identified in sequencing studies (PMID: 28769798), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
M160R missense unknown TP53 M160R lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). M160R has been identified in the scientific literature (PMID: 14559903), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R158fs frameshift loss of function - predicted TP53 R158fs results in a change in the amino acid sequence of the Tp53 protein beginning at 158 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the Tp53 DNA binding domain (UniProt.org), R158fs is predicted to lead to a loss of Tp53 protein function.
F113Y missense unknown TP53 F113Y lies within the DNA-binding domain of the Tp53 protein (UniProt.org). F113Y has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
N131fs frameshift loss of function - predicted TP53 N131fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 131 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), N131fs is predicted to lead to a loss of Tp53 protein function.
D259G missense unknown TP53 D259G lies within the DNA-binding domain of the Tp53 protein (UniProt.org). D259G has been identified in the scientific literature (PMID: 21232794), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
exon5 unknown unknown TP53 exon 5 indicates an unspecified mutation has occurred in exon 5 of the TP53 gene.
Q167L missense unknown TP53 Q167L lies within the DNA-binding domain of the Tp53 protein (PMID: 21760703). Q167L has been identified in the scientific literature (PMID: 11275993), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S121A missense gain of function - predicted TP53 S121A lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). S121A is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
P295L missense unknown TP53 P295L lies within the DNA-binding domain of the Tp53 protein (PMID: 20978130). P295L has been identified in the scientific literature (PMID: 22866089), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P151S missense loss of function TP53 P151S lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). P151S results in a loss of Tp53 transactivation activity and resistance to anoikis in cell culture, and promotes tumor growth in xenograft models (PMID: 21903770, PMID: 23625637).
R181S missense unknown TP53 R181S lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). R181S has been identified in sequencing studies (PMID: 21232794), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
H179R missense loss of function TP53 H179R lies within the DNA binding region of the Tp53 protein (UniProt.org). H179R results in a loss of Tp53 protein function as indicated by failure to activate downstream gene transcription and increased survival (PMID: 17361096, PMID: 26585234), and also induces cancer gene signature through activation of Ras signaling (PMID: 22427690).
I195F missense unknown TP53 I195F lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). I195F has been identified in sequencing studies (PMID: 27276561, PMID: 25534115), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R248L missense loss of function TP53 R248L is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248L results in decreased Tp53 transactivation and repression, and resistance to apoptosis in cell culture (PMID: 8336941, PMID: 20570896, PMID: 18566217).
R175L missense loss of function TP53 R175L is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R175L results in a decrease in Tp53 transactivation activity and reduced ability to induce apoptosis in cell culture (PMID: 16707427).
Y220C missense loss of function - predicted TP53 Y220C is a hotspot mutation that lies within the DNA-binding domain (PMID: 17401432). Y220C is predicted to confer a loss of function to the Tp53 protein, as demonstrated by decreased Tp53 transcriptional activity in cell culture (PMID: 16861262, PMID: 23630318).
S96A missense unknown TP53 S96A lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S96A has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P190R missense unknown TP53 P190R lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P190R has been identified in the scientific literature (PMID: 24186140, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
K320T missense loss of function - predicted TP53 K320T lies within the bipartite nuclear localization signal and HIPK1, CARM1, and HIPK2-interacting region of the Tp53 protein (UniProt.org). K320T results in defective nuclear localization of Tp53 in cell culture (PMID: 23416275, PMID: 22380534), which may result in a loss of Tp53 function.
T256I missense unknown TP53 T256I lies within the DNA-binding domain and the HIPK1, ZNF385A, AXIN1, and E4F1-interacting region of the Tp53 protein (UniProt.org). T256I has been identified in the scientific literature (PMID: 19558684), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
A161G missense unknown TP53 A161G lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A161G has been identified in the scientific literature (PMID: 27813088), but has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
N239I missense unknown TP53 N239I lies within the DNA-binding domain of the Tp53 protein (UniProt.org). N239I has been identified in sequencing studies (PMID: 22493262), but has not been biochemically characterized and therefore, its effect on Tp53 protein is unknown (PubMed, Nov 2018).
P322R missense unknown TP53 P322R lies within the CARM1, HIPK1, and HIPK2-interacting region of the Tp53 protein (UniProt.org). P322R has been identified in the scientific literature (PMID: 10225439), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
Y236C missense loss of function TP53 Y236C lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). Y236C demonstrates decreased Tp53 transactivation activity in cell culture (PMID: 16827139, PMID: 25634208).
R273* nonsense loss of function - predicted TP53 R273* results in a premature truncation of the Tp53 protein at amino acid 273 of 393 (UniProt.org). Due to the loss of the tetramerization domain (PMID: 22713868), R273* is predicted to lead to a loss of Tp53 function.
E298* nonsense loss of function - predicted TP53 E298* results in a premature truncation of the Tp53 protein at amino acid 298 of 393 (UniProt.org). Due to the loss of the tetramerization domain (PMID: 22713868), R298* is predicted to lead to a loss of Tp53 function.
H193L missense unknown TP53 H193L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). H193L has been identified in the scientific literature (PMID: 21056685), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R280D missense loss of function TP53 R280D lies within the DNA binding region of the Tp53 protein (UniProt.org). R280D confers a loss of function to the Tp53 protein as demonstrated by lack of DNA binding ability and impaired oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 7651437, PMID: 18524770).
R335fs frameshift unknown TP53 R335fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 335 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). R335fs has been identified in the scientific literature (PMID: 26272063), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S99P missense unknown TP53 S99P lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S99P has been identified in the scientific literature (PMID: 12826609), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C277F missense loss of function TP53 C277F lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C277F results in decreased DNA binding, reduced activation of Tp53 target genes, and reduced growth suppression activity in cultured cells (PMID: 12034820, PMID: 19850740, PMID: 18524770).
K319R missense unknown TP53 K319R lies within the HIPK1, HIPK2, and CARM1-interacting region and bipartite nuclear localization signal region of the Tp53 protein (UniProt.org). K319R demonstrates binding to Daxx similar to the level of wild-type Tp53 in yeast (PMID: 15364927), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C141R missense unknown TP53 C141R lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C141R has been identified in the scientific literature (PMID: 21483000), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S227F missense unknown TP53 S227F lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). S227F has been identified in the scientific literature (PMID: 16818615, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
F212fs frameshift loss of function - predicted TP53 F212fs results in a change in the amino acid sequence of the Tp53 protein beginning at 212 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of several functional domains (UniProt.org), F212fs is predicted to lead to a loss of Tp53 protein function.
P142L missense unknown TP53 P142L lies within the DNA binding domain of the Tp53 protein (PMID: 21760703). P142L is unable to transactivate reporter genes in yeast assays (PMID: 17311302), but has not been functionally characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
G266E missense loss of function TP53 G266E lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G266E results in decreased Tp53 transactivation activity (PMID: 20505364), and has been shown to promote cell motility in culture (PMID: 22114072).
P278L missense unknown TP53 P278L lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). P278L results in a loss of transactivation activity in yeast assays (PMID: 16861262), but has not been biochemically characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
K291T missense gain of function - predicted TP53 K291T lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). K291T is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
P278A missense unknown TP53 P278A lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). P278A has not been characterized in human cells, but demonstrates transcription activity similar to wild-type Tp53 in yeast (PMID: 20407015).
G245R missense unknown TP53 G245R is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245R has been identified in the scientific literature (PMID: 17041903), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
A276V missense unknown TP53 A276V lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A276V has been identified in sequencing studies (PMID: 21232794), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
M44fs frameshift loss of function - predicted TP53 M44fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 44 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the DNA-binding domain as well as several other functional domains (UniProt.org), M44fs is predicted to lead to a loss of Tp53 protein function.
V122E missense unknown TP53 V122E lies within the DNA-binding domain and CCAR2, HIPK1, ZNF385A, FBXO42, and AXIN1-interacting regions of the Tp53 protein (UniProt.org). V122E has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
L289D missense loss of function - predicted TP53 L289D lies within the DNA binding region of the Tp53 protein (UniProt.org). L289D is predicted to confer a loss of function to the Tp53 protein as demonstrated by reduced oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 18524770).
V274F missense loss of function TP53 V274F lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). V274F results in decreased Tp53 transactivation activity and reduced induction of apoptosis, but retains some context-dependent growth suppression in cell culture (PMID: 12782597).
C124S missense gain of function - predicted TP53 C124S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C124S is predicted to confer a gain of function to the Tp53 protein, as demonstrated by enhanced DNA binding capacity as compared to wild-type Tp53 in cell culture (PMID: 12034820).
C242R missense unknown TP53 C242R lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). C242R results in decreased transactivation activity in a yeast-based assay (PMID: 17947339).
P151L missense unknown TP53 P151L lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P151L has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P223T missense unknown TP53 P223T lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P223T has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P177L missense unknown TP53 P177L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). P177L demonstrates transactivation activity similar to wild-type Tp53 in a yeast assay (PMID: 9627118), but has not been characterized in human cells and therefore its effect on Tp53 protein function is unknown.
Y163H missense unknown TP53 Y163H lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). Y163H has been identified in the scientific literature (PMID: 27179933, PMID: 17764544, PMID: 28245875), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Dec 2018).
E339K missense no effect TP53 E339K lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). E339K demonstrates similar ability to regulate expression of Tp53 targets and induce apoptosis in culture (PMID: 24076587).
P47S missense unknown TP53 P47S lies within the N-terminal domain of the Tp53 protein (PMID: 15510160). P47S is a common polymorphism in Tp53 with conflicting impact on Tp53 function, demonstrating activity similar to wild-type in one study, and reduced transactivation of Tp53 targets and resistance to apoptosis in another (PMID: 25584008, PMID: 27034505).
R283C missense loss of function TP53 R283C lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R283C leads to a reduction in Tp53 transactivation activity, and the corresponding mouse variant (R277C) demonstrates decreased ability to prevent TgfB-induced epithelial-to-mesenchymal transition in culture (PMID: 22710932, PMID: 23018556).
R333P missense unknown TP53 R333P lies within the HIPK1, CARM1, and HIPK2-interacting and the oligomerization region of the Tp53 protein (UniProt.org). R333P results in a monomer Tp53 protein and loss of Tp53 transcriptional activity in yeast (PMID: 16007150), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
D324A missense unknown TP53 D324A lies within the tetramerization domain of the Tp53 protein (PMID: 15510160). D324A demonstrated increased transcription activity and tetramerization ability similar to wild-type Tp53 in yeast (PMID: 16007150).
E286G missense unknown TP53 E286G lies within the DNA-binding domain of the Tp53 protein (PMID: 11902578). E286G results in defects in Tp53 transactivation activity (PMID: 11313981), and does not affect transactivation activity of wild-type Tp53 in yeast assays (PMID: 11896595), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
P152fs frameshift loss of function - predicted TP53 P152fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 152 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), P152fs is predicted to lead to a loss of Tp53 protein function.
C141Afs*5 frameshift loss of function - predicted TP53 C141Afs*5 indicates a shift in the reading frame starting at amino acid 141 and terminating 5 residues downstream causing a premature truncation of the 393 amino acid Tp53 protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (UniProt.org, PMID: 21561095), C141Afs*5 is predicted to lead to a loss of Tp53 protein function.
Y234S missense unknown TP53 Y234S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). Y234S has been identified in sequencing studies (PMID: 24667986, PMID: 24662767), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S121F missense gain of function - predicted TP53 S121F lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). S121F is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
F212C missense unknown TP53 F212C lies within the DNA-binding domain of the Tp53 protein (UniProt.org). F212C has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
C242Y missense loss of function - predicted TP53 C242Y lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C242Y is predicted to confer a loss of function to the Tp53 protein, as demonstrated by abolished ZBP-89 interaction in culture (PMID: 12759240).
C135W missense unknown TP53 C135W lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C135W has been identified in the scientific literature (PMID: 18765419), but has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R175A missense loss of function - predicted TP53 R175A is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R175A results in a small decrease in Tp53 DNA-binding affinity and stability in cell culture (PMID: 10713666), and is therefore predicted to confer a loss of function to the Tp53 protein.
L308R missense unknown TP53 L308R lies within the HIPK1, CCAR2, and CARM1-interacting region and bipartite nuclear localization signal motif of the Tp53 protein (UniProt.org). L308R has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
E204G missense unknown TP53 E204G lies within the DNA-binding domain of the Tp53 protein (UniProt.org). E204G has been identified in the scientific literature (PMID: 8344494, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
C141S missense unknown TP53 C141S lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C141S retains partial Tp53 transactivation activity in a yeast assay (PMID: 19681600), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
G245_M246insAMC insertion unknown TP53 G245_M246insAMC results in the insertion of three amino acids in the DNA-binding domain of the Tp53 protein between amino acids 245 and 246 (UniProt.org). G245_M246insAMC has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
T377S missense unknown TP53 T377S lies within the region of the Tp53 protein involved in repression of DNA binding and the CARM1-interacting region (UniProt.org). T377S has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
G266R missense loss of function - predicted TP53 G266R lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G266R is predicted to confer a loss of function to the Tp53 protein as demonstrated by decreased Tp53 transactivation activity in cell culture (PMID: 16827139).
over exp none no effect TP53 over exp indicates an over expression of the Tp53 protein. However, the mechanism causing the over expression is unspecified.
P219S missense loss of function TP53 P219S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). P219S results in decreased Tp53 transactivation activity and inability to suppress colony formation in cell culture (PMID: 25584008).
G245V missense loss of function TP53 G245V is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245V results in decreased Tp53 transactivation and transrepression activity and decreased growth suppression ability compared to wild-type Tp53 in cell culture (PMID: 8001119).
E171V missense unknown TP53 E171V lies within the DNA-binding domain of the Tp53 protein (UniProt.org). E171V has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
L330R missense loss of function TP53 L330R lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). L330R results in decreased Tp53 tetramerization and loss of Tp53 transcriptional activity in cell culture (PMID: 19454241, PMID: 24816189).
V122M missense unknown TP53 V122M lies within the DNA-binding domain and CCAR2, HIPK1, ZNF385A, FBXO42, and AXIN1-interacting regions of the Tp53 protein (UniProt.org). V122M has been identified in the scientific literature (PMID: 28477877), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
A74T missense unknown TP53 A74T lies within the CCAR2, HRMT1L2, and WWOX-interacting regions of the Tp53 protein (UniProt.org). A74T has been identified in sequencing studies (PMID: 19336573), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
D324H missense unknown TP53 D324H lies within the tetramerization domain of the Tp53 protein (PMID: 15510160). D324H demonstrated increased transcription activity and tetramerization ability similar to wild-type Tp53 in yeast (PMID: 16007150).
G105A missense unknown TP53 G105A lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G105A has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
M246A missense unknown TP53 M246A lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). M246A results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
T170P missense unknown TP53 T170P lies within the DNA-binding domain and the CCAR2, HIPK1, ZNF385A, FBXO42 and AXIN1-interacting regions of the Tp53 protein (UniProt.org). T170P has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R280I missense unknown TP53 R280I lies in a DNA contact site within the DNA-binding domain of the Tp53 protein (PMID: 21056992). R280I has been identified in sequencing studies (PMID: 27167113, PMID: 25695693), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown.
T211I missense unknown TP53 T211I lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). T211I confers temperature-sensitivity to the Tp53 protein with lowest transactivation activity at an elevated temperature in a yeast assay (PMID: 22710932), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
C242S missense loss of function TP53 C242S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C242S results in decreased Tp53 binding to DNA in cell culture (PMID: 17170001), decreased interaction with MIF (PMID: 18502749), decreased nuclear translocation of YB1 (PMID: 12743601), decreased Tp53 protein stability (PMID: 10713666), and leads to a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015).
L111Q missense unknown TP53 L111Q lies within the DNA-binding domain and CCAR2, HIPK1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). L111Q has been identified in the scientific literature (PMID: 27179933, PMID: 25471132), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P98R missense unknown TP53 P98R lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). P98R has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S240R missense loss of function TP53 S240R lies within the DNA binding domain and HIPK1, ZNF385A and AXIN1-interacting region of the p53 protein (UniProt.org). S240R confers a loss of function to Tp53 as demonstrated by decreased Tp53 transactivation activity and decreased ability to induce apoptosis, but retains growth suppression activity in cell culture (PMID: 12509279, PMID: 10229196, PMID: 25881545).
S33A missense unknown TP53 S33A lies within the transcription activation region and the HRMT1L2-interacting region of the Tp53 protein (UniProt.org). S33A demonstrates Slk-stimulated transcriptional activity similar to wild-type Tp53 in culture in one study (PMID: 19640899), but decreased transcriptional response to CDDP in another study (PMID: 10811125), therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
I254N missense loss of function - predicted TP53 I254N lies within the DNA-binding domain of the Tp53 protein (PMID: 11902578). I254N results in temperature-dependent alterations in Tp53 transactivation activity with decreased transactivation at physiological temperatures (PMID: 20505364), and is associated with Tp53 over expression in patient-derived samples (PMID: 26564006), and therefore is predicted to confer a loss of function to the Tp53 protein.
E224* nonsense loss of function - predicted TP53 E224* results in a premature truncation of the Tp53 protein at amino acid 224 of 393 (UniProt.org). Due to the loss of several functional domains (UniProt.org), E224* is predicted to lead to a loss of Tp53 protein function.
K320R missense loss of function TP53 K320R lies within the nuclear localization signal of the Tp53 protein (PMID: 11420669). K320R leads to decreased activation of select Tp53 targets and resistance to apoptosis in cell culture (PMID: 14695212, PMID: 15831478).
P190A missense unknown TP53 P190A lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P190A has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
E298V missense unknown TP53 E298V lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). E298V has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S227fs frameshift loss of function - predicted TP53 S227fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 227 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the oligomerization domain (UniProt.org), S227fs is predicted to lead to a loss of Tp53 protein function.
T211S missense unknown TP53 T211S lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). T211S has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
N247D missense unknown TP53 N247D lies within the DNA-binding domain and the AXIN1, 53BP2 SH3 domain and E4F1-interacting region of the Tp53 protein (UniProt.org). N247D has been identified in the scientific literature (PMID: 22866089, PMID: 21232794, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2017).
M243T missense unknown TP53 M243T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). M243T results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore its effect on Tp53 protein function is unknown.
I254T missense loss of function TP53 I254T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). I254T results in decreased Tp53 transactivation activity and reduced ability to suppress colony formation in cell culture (PMID: 25584008).
R273Y missense unknown TP53 R273Y is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R273Y has been identified in the scientific literature (PMID: 29026176), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
H297R missense unknown TP53 H297R lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H297R has been identified in sequencing studies (PMID: 28667006), but has not been biochemically characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S215G missense loss of function TP53 S215G lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). S215G results in decreased Tp53 transactivation activity and leads to reduced apoptosis relative to wild type Tp53 in cell culture (PMID: 22862161).
R273P missense loss of function TP53 R273P is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R273P results in decreased activation of the Tp53 target gene p21, and exerts a dominant-negative effect on wild-type Tp53 protein in cell culture (PMID: 22484423).
K292I missense gain of function - predicted TP53 K292I lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). K292I is predicted to confer a gain of function to the Tp53 protein as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
V122fs frameshift loss of function - predicted TP53 V122fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 122 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), V122fs is predicted to lead to a loss of Tp53 protein function.
F134Y missense loss of function TP53 F134Y lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). F134Y results in decreased Tp53 transactivation activity and reduced ability to suppress colony formation in cell culture (PMID: 25584008).
E198* nonsense loss of function - predicted TP53 E198* results in a premature truncation of the Tp53 protein at amino acid 198 of 393 (UniProt.org). Due to the loss of several functional domains (UniProt.org), E198* is predicted to lead to a loss of Tp53 protein function.
P359L missense unknown TP53 P359L lies within the CARM1, HIPK2, and USP7-interacting region of the Tp53 protein (UniProt.org). P359L has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
V147A missense unknown TP53 V147A lies within the DNA-binding domain and CCAR2, HIPK1, ZNF385A, FBXO42, and AXIN1-interacting regions of the Tp53 protein (UniProt.org). V147A has been identified in sequencing studies (PMID: 30048458), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
A119P missense unknown TP53 A119P lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A119P has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Sep 2018).
Y163* nonsense loss of function - predicted TP53 Y163* results in a premature truncation of the Tp53 protein at amino acid 163 of 393 (UniProt.org). Due to the loss of several functional domains (UniProt.org), Y163* is predicted to lead to a loss of Tp53 protein function.
A159P missense unknown TP53 A159P lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). A159P has not been fully biochemically characterized, but demonstrates binding to ZBP-89 at similar level of wild-type Tp53 in culture (PMID: 12759240).
L344R missense loss of function TP53 L344R lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). L344R results in a decreased Tp53 tetramerization and transcriptional activity in cell culture (PMID: 19454241, PMID: 20505364).
R158G missense loss of function - predicted TP53 R158G lies within the DNA-binding domain of the Tp53 protein (PMID: 21760703). R158G leads to the loss of Tp53 DNA binding activity in an in vitro assay, and interferes with transactivation by wild-type Tp73 in yeast (PMID: 9472631, PMID: 12917626), and therefore is predicted to confer a loss of function to the Tp53 protein.
H168N missense no effect TP53 H168N lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). H168N demonstrates DNA binding ability and exonuclease activity comparable to wild-type p53 in cell-free assays (PMID: 19462533).
S240I missense unknown TP53 S240I lies within the DNA-binding domain and HIPK1, ZNF385A, and AXIN1-interacting region of the Tp53 protein (UniProt.org). The functional effect of S240I is conflicting, as it has been reported to reduced Tp53 transactivation activity, but retains growth suppression ability in cell culture (PMID: 10901165).
V197L missense loss of function - predicted TP53 V197L lies within the DNA-binding domain and HIPK1, ZNF385A, FBXO42 and AXIN-interacting region of the Tp53 protein (UniProt.org). V197L results in a temperature-dependent decrease in Tp53 transcriptional activity at 37 degrees, and is associated with decreased induction of apoptosis in cultured cells (PMID: 11668476), and therefore is predicted to confer a loss of function to the Tp53 protein.
H168R missense loss of function TP53 H168R lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H168R confers a loss of function to the Tp53 protein, as demonstrated by decreased Tp53 transactivation activity and decreased induction of apoptosis in cell culture (PMID: 18996393).
P278R missense loss of function - predicted TP53 P278R lies within the DNA binding domain of the Tp53 protein (UniProt.org). P278R is predicted to result in a loss of Tp53 protein function as indicated by the inability of corresponding mouse P275R to induce Tp53 target gene expression of p21 and Noxa (PMID: 20195489).
K320Q missense loss of function TP53 K320Q lies within the HIPK1, HIPK2 and CARM1-interacting region of the Tp53 protein (UniProt.org). K320Q is able to activate p21, but results in alterations in other Tp53 transcriptional and repressive activities, and leads to resistance to apoptosis in cell culture (PMID: 15831478, PMID: 16717128).
S9N missense unknown TP53 S9N lies within the CCAR2 and HRMT1L2-interacting region and the transcription activation region of the Tp53 protein (UniProt.org). S9N has been identified in the scientific literature (PMID: 12826609), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S99A missense unknown TP53 S99A lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S99A has been identified in the scientific literature (PMID: 12826609), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S366Y missense unknown TP53 S366Y lies within HIPK1, CARM1, and HIPK2-interacting region of the Tp53 protein (UniProt.org). S366Y has been identified in the scientific literature (PMID: 12826609), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C135F missense loss of function - predicted TP53 C135F lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C135F is predicted to confer a loss of function to the Tp53 protein, as demonstrated by loss of Tp53 transactivation activity in culture (PMID: 16492679).
T140S missense unknown TP53 T140S lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42, CCAR2 and AXIN1-interacting regions of the Tp53 protein (UniProt.org). T140S has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C238Y missense no effect TP53 C238Y lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). C238Y results in binding to MDM2, phosphorylation, and transactivation of Tp53 target genes similar to wild-type Tp53 in cell culture, and does not significantly alter Tp53 structure in molecular models (PMID: 16818505).
T118fs frameshift loss of function - predicted TP53 T118fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 118 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), T118Qfs*5 is predicted to lead to a loss of Tp53 protein function.
G154S missense unknown TP53 G154S lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G154S has been identified in the scientific literature (PMID: 27782820), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
A159G missense unknown TP53 A159G lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). A159G has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Sep 2018).
G154A missense unknown TP53 G154A lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G154A has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
T284A missense no effect TP53 T284A lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). T284A does not impair oligomerization of the pro-apoptotic protein Bak (PMID: 18524770), and induces the expression of its target genes p21 and Bak similar to wild-type Tp53 in a cell culture assay (PMID: 20959462).
R158L missense loss of function - predicted TP53 R158L lies within the DNA-binding domain of the Tp53 protein (UniProt.org). R158L is predicted to confer a loss of function to the Tp53 protein as demonstrated by decreased Tp53 transactivation activity, but does not interfere with wild-type Tp53 activity in cell culture (PMID: 16861262, PMID: 25584008).
C275F missense unknown TP53 C275F lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C275F has been identified in sequencing studies (PMID: 26873401, PMID: 24682512, PMID: 27095739), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
D324Y missense unknown TP53 D324Y lies within the tetramerization domain of the Tp53 protein (PMID: 15510160). D324Y demonstrated increased Tp53 transcription activity in yeast (PMID: 16007150).
G244C missense unknown TP53 G244C lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G244C has been identified in the scientific literature (PMID: 11307149), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
I195* nonsense loss of function - predicted TP53 I195* results in a premature truncation of the Tp53 protein at amino acid 195 of 393 (UniProt.org). Due to the loss of the DNA binding domain including sites that interact with Mre11 (UniProt.org, PMID: 22713868), I195* is predicted to lead to a loss of Tp53 protein function.
C277S missense gain of function - predicted TP53 C277S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C277S is predicted to confer a gain of function to the Tp53 protein, as demonstrated by enhanced DNA binding capacity as compared to wild-type Tp53 in cell culture (PMID: 12034820).
H193R missense loss of function - predicted TP53 H193R lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H193R has not been biochemically characterized in human cells, but results in decreased Tp53 transactivation ability in yeast assays and is predicted to result in decreased Tp53 stability and protein expression by computational modeling (PMID: 9627118, PMID: 21763698).
H297L missense unknown TP53 H297L lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H297L has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R249T missense unknown TP53 R249T is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R249T is predicted to confer a loss of function to Tp53 in computer models (PMID: 9724739), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
F338S missense unknown TP53 F338S lies within the HIPK1, CARM1 and HIPK2-interacting and the oligomerization region of the Tp53 protein (UniProt.org). F338S results in decreased Tp53 transcriptional activity in yeast assays (PMID: 16007150), but has not been biochemically characterized in human cells, and therefore its effect on Tp53 protein function is unknown.
K319E missense unknown TP53 K319E lies within the HIPK1, CARM1 and HIPK2-interacting region of the Tp53 protein (UniProt.org). K319E has been identified in sequencing studies (PMID: 29085664), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S20fs frameshift loss of function - predicted TP53 S20fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 20 of 393, likely resulting in premature truncation of the functional protein. Due to the loss of all known functional domains (UniProt.org), S20fs is predicted to lead to a loss of Tp53 protein function.
H179Y missense loss of function TP53 H179Y lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). H179Y confers a loss of function to the Tp53 protein as indicated by decreased transactivation of Tp53 targets, decreased growth suppression activity, decreased suppression of Nrf2 expression, and increased Ccna1 and Cdk4 expression and cell proliferation in culture (PMID: 17530187, PMID: 12509279, PMID: 26497680).
V216M missense loss of function - predicted TP53 V216M lies within the DNA-binding domain of the Tp53 protein (UniProt.org). V216M results in decreased Tp53 transactivation activity in cultured cells (PMID: 20505364), and is therefore predicted to confer a loss of function to the Tp53 protein.
M246R missense loss of function - predicted TP53 M246R lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). M246R results in a loss of Tp53 binding to SV40 large T-antigen (LTag) (PMID: 16951253), and therefore is predicted to confer a loss of function to the Tp53 protein.
H296Y missense unknown TP53 H296Y lies within the DNA-binding domain of the Tp53 protein (PMID: 20978130). H296Y has been identified in sequencing studies (PMID: 27288520), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R213Q missense loss of function - predicted TP53 R213Q lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). R213Q results in a mild increase in cell proliferation in culture and increased tumor growth in animal models (PMID: 8080050), and therefore is predicted to confer a loss of function to the Tp53 protein.
Y327L missense unknown TP53 Y327L (also referred to as Y326L) lies within the transactivation domain of the Tp53 protein (PMID: 22713868). Y327L confers similar sensitivity to mutant Tp53-targeted therapeutics compared to cells with characterized Tp53 mutations in culture (PMID: 26748848), however, has not been biochemically characterized and therefore its effect on Tp53 function is unknown.
Q100P missense unknown TP53 Q100P lies within DNA-binding domain of the Tp53 protein (PMID: 21760703). Q100P has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R280T missense loss of function TP53 R280T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). R280T results in a loss of Tp53 transactivation activity and is transforming in cell culture (PMID: 16616891, PMID: 8464896).
S241Y missense loss of function TP53 S241Y lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). S241Y results in a loss of Tp53 transactivation activity and decreased ability to suppress colony formation in cell culture (PMID: 25584008).
R282D missense loss of function TP53 R282D lies within the DNA binding region of the Tp53 protein (UniProt.org). R282D confers a loss of function to the Tp53 protein as demonstrated by lack of DNA binding ability and impaired oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 7651437, PMID: 18524770).
H179D missense unknown TP53 H179D lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H179D has been identified in sequencing studies (PMID: 24128716), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
G117E missense unknown TP53 G117E lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). G117E results in decreased Tp53 transcriptional activity in a yeast assay (PMID: 11429700), but has not been biochemically characterized in human cells and therefore, its effect on Tp53 function is unknown.
G262R missense unknown TP53 G262R lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G262R has been identified in sequencing studies (PMID: 23243274), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
D324N missense unknown TP53 D324N lies within the tetramerization domain of the Tp53 protein (PMID: 15510160). D324N demonstrated increased transcription activity and tetramerization ability similar to wild-type Tp53 in yeast (PMID: 16007150).
P295A missense unknown TP53 P295A lies within the DNA-binding domain of the Tp53 protein (PMID: 20978130). P295A has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
L114fs frameshift loss of function - predicted TP53 L114fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 114 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to disruption of the DNA binding region and loss of the oligomerization domain (UniProt.org), L114fs is predicted to lead to a loss of Tp53 protein function.
G334W missense unknown TP53 G334W lies within the hinge residue of the oligomerization domain of the Tp53 protein (PMID: 16007150). G334W results in a loss of Tp53 transactivation activity in yeast (PMID: 16007150), but has not been characterized in human cells and therefore, its effect on Tp53 function is unknown.
R196G missense loss of function - predicted TP53 R196G lies within the DNA binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1 interaction region of the Tp53 protein (UniProt.org). R196G is predicted to confer a loss of function to the Tp53 protein, as demonstrated by decreased transactivation activity of Tp53 in culture (PMID: 22710932).
N235D missense loss of function TP53 N235D lies within the DNA binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1 interaction region of the Tp53 protein (UniProt.org). N235D results in decreased Tp53 transactivation activity and fails to suppress colony formation in cell culture (PMID: 25584008).
G245C missense loss of function TP53 G245C is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245C results in a loss of transactivation of several targets of wild-type Tp53 (PMID: 22170099, PMID: 30126368), and also confers a gain-of-function to Tp53, as demonstrated through inhibition of Ampk activation in cell culture, and leads to increased tumor formation in mouse models (PMID: 24857548), and increased migration and invasion in culture (PMID: 30126368).
H178N missense unknown TP53 H178N lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H178N has been identified in sequencing studies (PMID: 26366557), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
P300R missense unknown TP53 P300R lies within the HIPK1, CCAR2, CARM1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). P300R has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
T155P missense unknown TP53 T155P lies within the DNA-binding core domain of the Tp53 protein (PMID: 21561095). T155P has been identified in the scientific literature (PMID: 22991414, PMID: 24766216, PMID: 20385133), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Feb 2018).
R158H missense loss of function TP53 R158H lies within the DNA binding domain of the Tp53 protein (UniProt.org). R158H results in decreased Tp53 transactivation activity and reduced ability to suppress colony formation in cell culture (PMID: 25584008).
D7A missense loss of function - predicted TP53 D7A lies within the interaction with HRMT1L2 and transcription activation region of the Tp53 protein (UniProt.org). D7A is predicted to confer a loss of function to the Tp53 protein as demonstrated by reduced Pimpt-mediated Tp53 methylation (PMID: 22735455).
F109L missense unknown TP53 F109L lies within the DNA-binding domain of the Tp53 protein (UniProt.org). F109L has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
K292T missense gain of function - predicted TP53 K292T lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). K292T is predicted to confer a gain of function to the Tp53 protein as demonstrated by increased ability to induce apoptosis in cultured cells when compared to wild-type Tp53 (PMID: 15781620).
N311S missense unknown TP53 N311S lies within the HIPK1-interacting region of the Tp53 protein (UniProt.org). N311S has been identified in the scientific literature (PMID: 24076587), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R337P missense loss of function TP53 R337P lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). R337P results in decreased Tp53 tetramerization and transactivation activity and increased colony formation in cell culture (PMID: 19454241, PMID: 29955864).
T211A missense unknown TP53 T211A lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). T211A demonstrated resistance to transcriptional activity suppression by AurkB in vitro (PMID: 22611192), but has not been fully biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R175G missense loss of function - predicted TP53 R175G is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R175G results in decreased Tp53 transactivation activity in cell culture (PMID: 28472496) and therefore, it is predicted to result in a loss of Tp53 protein function.
D228N missense unknown TP53 D228N lies within the DNA-binding domain of the Tp53 protein (UniProt.org). D228N has been identified in sequencing studies (PMID: 26317919), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
Y107N missense unknown TP53 Y107N lies within the DNA-binding domain and CCAR2, WWOX, HIPK1, and ZNF385A-interacting regions of the Tp53 protein (UniProt.org). Y107N has been identified in sequencing studies (PMID: 27612322), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
F341C missense loss of function - predicted TP53 F341C lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). F341C results in decreased Tp53 tetramerization in cell culture and reduced Tp53 transcriptional activity in a reporter assay (PMID: 19454241), and is therefore predicted to confer a loss of function to the Tp53 protein.
L145Q missense unknown TP53 L145Q lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). L145Q has not been characterized, but is predicted to disrupt DNA binding of Tp53 by structural modeling (PMID: 21561095).
V173M missense loss of function - predicted TP53 V173M lies within the DNA binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). V173M is predicted to confer a loss of function to the Tp53 protein, as demonstrated by reduced Tp53 transactivation activity in cell culture (PMID: 15037740).
R290G missense gain of function - predicted TP53 R290G lies within the DNA-binding domain of the Tp53 protein (PMID: 20978130). R290G is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
C135fs frameshift loss of function - predicted TP53 C135fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 135 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to disruption of the DNA-binding domain and loss of the oligomerization domain (UniProt.org), C135fs is predicted to lead to a loss of Tp53 protein function.
R181C missense loss of function TP53 R181C lies within the DNA-binding domain and HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). R181C is able to transactivate the Tp53 targets p21 and PIG3, but does not transactivate other Tp53 targets including the apoptotic genes BAX and P53AIP1, and leads to decreased induction of apoptosis and enhances transformation in culture (PMID: 10229196, PMID: 20471942).
H179P missense unknown TP53 H179P lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H179P has been identified in the scientific literature (PMID: 25716545), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
I251S missense unknown TP53 I251S lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). I251S confers similar sensitivity to mutant Tp53-targeted therapeutics compared to cells with characterized Tp53 mutations in culture (PMID: 26748848), however, has not been biochemically characterized and therefore its effect on Tp53 protein function is unknown.
G245F missense unknown TP53 G245F is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245F has been identified in sequencing studies (PMID: 11051249), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Sep 2018).
K292Q missense unknown TP53 K292Q lies within the DNA-binding domain of the Tp53 protein (PMID: 20978130). K292Q has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R283A missense loss of function - predicted TP53 R283A lies within the DNA binding region of the Tp53 protein (UniProt.org). R283A is predicted to confer a loss of function to the Tp53 protein as demonstrated by impaired oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 18524770).
N310I missense unknown TP53 N310I does not lie within any known functional domains of the Tp53 protein (PMID: 20978130). N310I has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R280A missense loss of function TP53 R280A lies within the DNA binding region of the Tp53 protein (UniProt.org). R280A confers a loss of function to the Tp53 protein as demonstrated by loss of Tp53 DNA binding, impaired oligomerization of the pro-apoptotic protein Bak, and resistance to apoptosis (PMID: 7969167, PMID: 18524770).
R337H missense loss of function TP53 R337H lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). R337H demonstrates decreased Tp53 tetramerization and transactivation activity in cell culture (PMID: 19454241, PMID: 25584008), decreased transactivation activity and expression of DNA damage markers and increased tumorigenesis in mice harboring the corresponding mouse allele (PMID: 30042151), results in increased Tp53 nuclear accumulation in patient samples (PMID: 26452166), and has a pH-dependent effect on Tp53 stability and activity (PMID: 25584008, PMID: 11753428).
F134L missense loss of function - predicted TP53 F134L lies within the DNA binding region of the Tp53 protein (UniProt.org). F134L is predicted to confer a loss of function to the Tp53 protein as demonstrated by loss of Tp53-dependent DNA damage response (PMID: 14587098).
N235Y missense unknown TP53 N235Y lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). N235Y has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
N268I missense unknown TP53 N268I lies within the DNA-binding domain and the HIPK1, ZNF385A, AXIN1 and E4F1-interacting region of the Tp53 protein (UniProt.org). N268I has been identified in the scientific literature (PMID: 23200980, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2017).
G112C missense unknown TP53 G112C lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G112C has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S303G missense unknown TP53 S303G lies within the CCAR2, HIPK1, and CARM1-interacting region of the Tp53 protein (UniProt.org). S303G has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
V157P missense unknown TP53 V157P lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). V157P has not been fully biochemically characterized, but demonstrated binding to ZBP-89 at similar level of wild-type Tp53 in culture (PMID: 12759240).
L111fs frameshift loss of function - predicted TP53 L111fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 111 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), L111fs is predicted to lead to a loss of Tp53 protein function.
C238F missense loss of function - predicted TP53 C238F lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). C238F demonstrates decreased Tp53 transactivation activity in cell culture (PMID: 25634208), and therefore is predicted to confer a loss of function to the Tp53 protein.
V157F missense loss of function TP53 V157F lies within the DNA-binding core domain of the Tp53 protein (PMID: 21561095). V157F results in decreased DNA binding and activation of Tp53 targets, and also confers a gain of function to Tp53, resulting in aberrant gene activation in cell culture (PMID: 15077194, PMID: 16778209, PMID: 22710932).
E180K missense loss of function TP53 E180K lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). E180K confers a loss of function to the Tp53 protein, as indicated by alterations in the the proteolytic processing resulting in weak binding of BCL-xL, as well as decreased activation of downstream targets and reduced apoptosis in cell culture (PMID: 24814347).
P301Q missense unknown TP53 P301Q lies within the CCAR2, HIPK1, and CARM1-interacting region of the Tp53 protein (UniProt.org). P301Q has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
A159fs frameshift loss of function - predicted TP53 A159fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 159 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), A159fs is predicted to lead to a loss of Tp53 protein function.
P322S missense unknown TP53 P322S lies within the CARM1, HIPK1, and HIPK2-interacting region of the Tp53 protein (UniProt.org). P322S has been identified in the scientific literature (PMID: 25952750), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
N310S missense unknown TP53 N310S lies within the HIPK1, CCAR2, and CARM1-interacting regoin of the Tp53 protein (UniProt.org). N310S has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
E271K missense loss of function - predicted TP53 E271K lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). E271K is predicted to result in decreased Tp53 stability and reduced Tp53 protein expression by computational modeling (PMID: 21763698).
R249K missense unknown TP53 R249K is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R249K has been identified in the scientific literature (PMID: 27101868), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown.
C275* nonsense loss of function TP53 C275* results in a premature truncation of the Tp53 protein at amino acid 275 of 393 (UniProt.org). C275* results in a loss of Tp53 transactivation activity and inability to suppress colony formation in cell culture (PMID: 25584008).
L344P missense loss of function TP53 L344P lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). L344P results in decreased Tp53 tetramerization and transcriptional activity, reduced expression of Tp53 target genes, and demonstrates partial colony suppression ability in cell culture (PMID: 19454241, PMID: 9125151, PMID: 20080630).
dec exp none no effect TP53 dec exp indicates decreased expression of the Tp53 protein. However, the mechanism causing the decreased expression is unspecified.
E285K missense loss of function TP53 E285K lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). E285K results in a temperature-dependent decrease in transcriptional activation by Tp53 in cell culture (PMID: 15613472, PMID: 22710932).
S303R missense unknown TP53 S303R lies within the CCAR2, HIPK1, and CARM1-interacting region of the Tp53 protein (UniProt.org). S303R has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
E336* nonsense loss of function TP53 E336* results in a premature truncation of the Tp53 protein at amino acid 336 of 393 (UniProt.org). E336* results in decreased Tp53 transactivation activity and reduced nuclear localization in cell culture (PMID: 9331090, PMID: 16969106).
P98A missense loss of function TP53 P98A lies within the WWOX-interacting region of the Tp53 protein (UniProt.org). P98A results in decreased Tp53 transactivation activity and leads to reduced apoptosis relative to wild-type Tp53 in cell culture (PMID: 22862161, PMID: 20505364).
E224K missense unknown TP53 E224K lies within the DNA-binding domain of the Tp53 protein (UniProt.org). E224K demonstrates defects in Tp53 transactivation activity in a yeast assay (PMID: 11429705), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
N131S missense unknown TP53 N131S lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). N131S has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P250L missense loss of function TP53 P250L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). P250L results in aggregation and decreased nuclear localization of Tp53, demonstrates decreased Tp53 transactivation activity, and interferes with wild-type Tp53 transactivation activity in cell culture (PMID: 21445056).
V203L missense unknown TP53 V203L lies within the DNA-binding domain and CCAR2, HIPK1, ZNF385A, FBXO42, and AXIN1-interacting regions of the Tp53 protein (UniProt.org). V203L has been identified in the scientific literature (PMID: 25331842), but has not been biochemically characterized and therefore, its effect on protein function is unknown (PubMed, Nov 2018).
D281E missense loss of function - predicted TP53 D281E lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). D281E results in loss of Tp53 binding to ZBP-89 in cell culture (PMID: 12759240), and also demonstrates a lack of Tp53 transactivation activity in an yeast assay (PMID: 20407015), and therefore is predicted to confer a loss of function to the Tp53 protein.
R273L missense loss of function TP53 R273L is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R273L results in decreased Tp53 transactivation and decreased transcriptional repression of Tp53 targets in cell culture (PMID: 10787423, PMID: 8336941).
M237V missense unknown TP53 M237V lies within the DNA-binding domain and the HIPK1, ZNF385A, and AXIN1-interacting region of the Tp53 protein (UniProt.org). M237V has been identified in the scientific literature (PMID: 27101868, PMID: 28160562), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
Y236F missense unknown TP53 Y236F lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). Y236F has been identified in the scientific literature (PMID: 16461916, PMID: 19683006), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R280M missense loss of function TP53 R280M lies within the DNA binding domain of the Tp53 protein (UniProt.org). R280M results in decreased DNA binding and activation of Tp53 target genes and resistance to apoptosis in cell culture (PMID: 21643018).
M160K missense unknown TP53 M160K lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). M160K has been identified in sequencing studies (PMID: 26837699), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C135Y missense loss of function TP53 C135Y lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C135Y confers a loss of function to the Tp53 protein as demonstrated by loss of binding to the Drosha complex and inability to induce downstream miRs and loss of transactivation activity in cell culture (PMID: 19626115, PMID: 8336941).
W53* nonsense loss of function - predicted TP53 W53* results in a premature truncation of the Tp53 protein at amino acid 53 of 393 (UniProt.org). Due to the loss of the DNA-binding domain as well as several other functional domains (UniProt.org), W53* is predicted to lead to a loss of Tp53 protein function.
P177S missense unknown TP53 P177S lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P177S has been identified in the scientific literature (PMID: 11896595, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2017).
A307S missense unknown TP53 A307S lies within the CARM1-interacting region of the Tp53 protein (UniProt.org). A307S has been identified in the scientific literature (PMID: 25220666, PMID: 16094622), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
K164M missense loss of function - predicted TP53 K164M lies within the DNA-binding domain and HIPK1, ZNF385A, FBXO42 and AXIN-interacting region of the Tp53 protein (UniProt.org). K164M is associated with reduced expression of the Tp53 target gene Cdkn1a (p21Cip1) in human tumor samples (PMID: 8797864), and is therefore predicted to confer a loss of function to the Tp53 protein.
P12S missense unknown TP53 P12S lies within the transcription activation region and HRMT1L2 and CCAR2-interacting region of the Tp53 protein (UniProt.org). P12S has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
L323R missense unknown TP53 L323R lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). L323R has been identified in sequencing studies (PMID: 10225439), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R110P missense loss of function TP53 R110P lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). R110P confers a loss of function on the Tp53 protein as indicated by increased aggregation, including aggregation with Tp63, and Tp73, decreased DNA binding and transactivation of Tp53 targets, and decreased Caspase 3/7 activity in culture (PMID: 21445056, PMID: 24076587).
P82Rfs*41 frameshift loss of function - predicted TP53 P82Rfs*41 indicates a shift in the reading frame starting at amino acid 82 and terminating 41 residues downstream causing a premature truncation of the 393 amino acid Tp53 protein (UniProt.org). Due to the loss of the DNA binding domain and the oligomerization domain (PMID: 15510160), P82Rfs*41 is predicted to lead to a loss of Tp53 protein function.
G108V missense unknown TP53 G108V lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G108V has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S392fs frameshift unknown TP53 S392fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 392 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). S392fs has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
K139M missense unknown TP53 K139M lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). K139M has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R337L missense loss of function TP53 R337L lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). R337L results in reduced Tp53 tetramerization and decreased DNA binding and transactivation activity in cell culture (PMID: 19454241, PMID: 9766574).
S185R missense unknown TP53 S185R lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). S185R has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
K164N missense unknown TP53 K164N lies within the DNA binding domain of the p53 protein (PMID: 15510160). K164N has been identified in the scientific literature (PMID: 16546179), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Aug 2017).
F341V missense unknown TP53 F341V lies within the HIPK1, CARM1 and HIPK2-interacting, oligomerization region, and nuclear export signal motif of the Tp53 protein (UniProt.org). F341V results in the inability to form Tp53 tetramers and decreased Tp53 transcriptional activity in yeast assays (PMID: 16007150), bu has not been biochemically characterized in human cells and therefore, its effect on Tp53 function is unknown.
M237_S241del deletion unknown TP53 M237_S241del results in the deletion of five amino acids in the DNA-binding domain and the HIPK1, ZNF385A and AXIN1-interacting region of the Tp53 protein (UniProt.org). M237_S241del has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R181G missense unknown TP53 R181G lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). R181G has been identified in the scientific literature (PMID: 11353048), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
exon7 unknown unknown TP53 exon 7 indicates an unspecified mutation has occurred in exon 7 of the TP53 gene.
M246I missense loss of function TP53 M246I lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). M246I confers a loss of function on Tp53 protein as indicated by reduced DNA binding, decreased transcription activity, and failure to induce apoptosis in cell culture (PMID: 10777217).
G154C missense unknown TP53 G154C lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G154C has been identified in sequencing studies (PMID: 26718964), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
P278H missense unknown TP53 P278H lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). P278H has been identified in sequencing studies (PMID: 25151357), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
P190S missense loss of function TP53 P190S lies within the DNA binding domain of the Tp53 protein (UniProt.org). P190S confers a loss of function to the Tp53 protein, as demonstrated by decreased suppression of Vimentin mRNA expression, decreased ability to suppress cell viability, increased cell migration, and increased cell invasion in cell culture (PMID: 28408749).
Y103* nonsense loss of function - predicted TP53 Y103* results in a premature truncation of the Tp53 protein at amino acid 103 of 393 (UniProt.org). Due to the loss of the majority of the DNA-binding domain as well as several other functional domains (UniProt.org), Y103* is predicted to lead to a loss of Tp53 protein function.
del deletion loss of function TP53 del indicates a deletion of the TP53 gene.
R174M missense unknown TP53 R174M lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). R174M has been identified in the scientific literature (PMID: 7767998), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
loss unknown loss of function TP53 loss indicates loss of the TP53 gene, mRNA, or protein.
Q100R missense unknown TP53 Q100R lies within DNA-binding domain of the Tp53 protein (PMID: 21760703). Q100R has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R282H missense unknown TP53 R282H is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R282H has been identified in the scientific literature (PMID: 10582680), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
T140I missense unknown TP53 T140I lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42, CCAR2 and AXIN1-interacting regions of the Tp53 protein (UniProt.org). T140I has been identified in the scientific literature (PMID: 27101868, PMID: 17962810), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
K101N missense unknown TP53 K101N lies within the CCAR2, WWOX, HIPK1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). K101N has been identified in the scientific literature (PMID: 20847049), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
L111P missense unknown TP53 L111P lies within the DNA-binding region of the Tp53 protein (UniProt.org). L111P has been identified in sequencing studies (PMID: 18772396, PMID: 27499911), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
M246T missense unknown TP53 M246T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). M246T results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
A189D missense unknown TP53 A189D lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A189D has been identified in the sequencing studies (PMID: 23835706), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
D259Y missense unknown TP53 D259Y lies within the DNA-binding domain of the Tp53 protein (UniProt.org). D259Y has been identified in the scientific literature (PMID: 22550420, PMID: 27859003), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
L22P missense unknown TP53 L22P lies within HRMT1L2 and CCAR2-interacting region and the transcription activation region of the Tp53 protein (UniProt.org). L22P has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
C124fs frameshift loss of function - predicted TP53 C124fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 124 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to disruption of the DNA-binding domain and loss of the oligomerization domain (UniProt.org), C124fs is predicted to lead to a loss of Tp53 protein function.
P190L missense unknown TP53 P190L lies within the DNA binding domain of the Tp53 protein (UniProt.org). P190L demonstrates transactivation activity similar to wild-type Tp53 at higher galactose levels and mild transactivation defects at lower galactose levels in yeast assays (PMID: 20407015), however, has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown (PubMed, Sep 2018).
P300A missense unknown TP53 P300A lies within the HIPK1, CCAR2, CARM1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). P300A has been identified in sequencing studies (PMID: 10084308), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C135S missense loss of function - predicted TP53 C135S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C135S is predicted to confer a loss of function to the Tp53 protein, as demonstrated by decreased DNA binding in cell culture (PMID: 12034820).
R248E missense unknown TP53 R248E is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248E has been identified in the scientific literature (PMID: 23958919, PMID: 10319873), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown.
R283P missense unknown TP53 R283P lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). R283P results in decreased transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
L130I missense unknown TP53 L130I lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). L130I has been identified in sequencing studies (PMID: 28949453, PMID: 26319365), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
L130R missense unknown TP53 L130R lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). L130R results in decreased transactivation activity in a yeast assay (PMID: 12826609), but has not been biochemically characterized in human cells, and therefore its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
H297P missense unknown TP53 H297P lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H297P has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S96P missense unknown TP53 S96P lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S96P demonstrates enhanced Tp53 transactivation activity in a yeast assay (PMID: 11313981), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
S106N missense unknown TP53 S106N lies within the DNA-binding domain and the WWOX, HIPK1 and ZNF385A-interacting region of the Tp53 protein (UniProt.org). S106N has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
D259N missense unknown TP53 D259N lies within the DNA-binding domain of the Tp53 protein (UniProt.org). D259N results in altered Tp53 transactivation activity in yeast assays (PMID: 11896595), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
A161P missense unknown TP53 A161P lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A161P has been identified in the scientific literature (PMID: 27813088), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
S183L missense unknown TP53 S183L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). S183L results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
K305N missense unknown TP53 K305N lies within the HIPK1-interacting region and the bipartite nuclear localization signal motif of the Tp53 protein (UniProt.org). K305N results in a loss of nuclear localization of Tp53, but retains the ability to interact with wild-type Tp53 and Mdm2 (PMID: 11127820), however, has not been fully biochemically characterized and therefore, its effect on Tp53 protein function is unknown.
I195S missense unknown TP53 I195S lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). I195S demonstrates a loss of Tp53 transactivation activity in a yeast assay (PMID: 23897043), but has not been characterized in human cells and therefore its effect on Tp53 protein function is unknown.
R280K missense gain of function TP53 R280K lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R280K results in decreased activation and repression of wild-type Tp53 target genes (PMID: 17070499, PMID: 16322760, PMID: 18472962), as well as a gain-of-function in activation of novel targets, and leads to increased cell migration and invasion, and increased cell survival (PMID: 18472962, PMID: 24763051).
R248W missense loss of function TP53 R248W is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248W results in decreased transactivation of Tp53 target genes, increased cell proliferation in culture, and increased tumorigenesis in mice, and leads to decreased ATM activation, resulting in increased genetic instability (PMID: 17417627, PMID: 14743206).
R342P missense loss of function TP53 R342P lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). R342P results in decreased Tp53 tetramerization and transactivation activity in cell culture (PMID: 19454241, PMID: 9766574).
K120E missense loss of function TP53 K120E lies within the DNA binding region of the Tp53 protein (UniProt.org). K120E confers a loss of function to the Tp53 protein as demonstrated by impaired oligomerization of the pro-apoptotic protein Bak, decreased transactivation of Tp53 targets, reduced apoptotic signaling, and decreased colony suppression activity compared to wild-type Tp53 in cell culture (PMID: 18524770, PMID: 27341992).
V143A missense loss of function TP53 V143A lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). V143A results in decreased DNA binding and Tp53 transactivation activity, and leads to increased colony formation in cell culture (PMID: 16827139, PMID: 10973264, PMID: 15077194).
L111M missense unknown TP53 L111M lies within the DNA-binding domain and the HIPK1 and ZNF385A-interacting region of the Tp53 protein (UniProt.org). L111M has been identified in sequencing studies (PMID: 26933808), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
V172F missense loss of function - predicted TP53 V172F lies within the DNA binding region of the Tp53 protein (UniProt.org). V172F is predicted to result in a loss of Tp53 function, as it demonstrates enhanced interaction with Mdm4 and confers context-dependent alterations in Tp53 stability (PMID: 26876197).
P151H missense loss of function TP53 P151H lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). P151H confers a loss of function to the Tp53 protein as demonstrated by decreased transactivation of select Tp53 targets and inability to repress autophagy in cell culture (PMID: 22673234, PMID: 18818522, PMID: 27533082).
C176F missense loss of function - predicted TP53 C176F lies within a zinc binding residue in the DNA-binding region of the Tp53 protein (UniProt.org). C176F is predicted to confer a loss of function to the Tp53 protein, as demonstrated by the inability to induce CDKN1A (p21) transcription in cell culture (PMID: 22090360).
H193Q missense unknown TP53 H193Q lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H193Q has been identified in the scientific literature (PMID: 23200980), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R282Q missense gain of function TP53 R282Q is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R282Q confers a gain of function to Tp53 as demonstrated by activation of PCNA and MDR-1 expression, increased IL-6, and results in increased growth of human cells in culture (PMID: 11920959).
I50S missense unknown TP53 I50S lies within the CCAR2 and HRMT1L2-interacting region and the TADII motif of the Tp53 protein (UniProt.org). I50S has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
K132Q missense unknown TP53 K132Q lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). K132Q results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 12779080).
P301fs frameshift loss of function - predicted TP53 P301fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 301 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the oligomerization domain (UniProt.org), P301fs is predicted to lead to a loss of Tp53 protein function.
R282W missense loss of function TP53 R282W is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R282W results in decreased activation of Tp53 targets and inhibits Ampk signaling, leading to invasive growth and altered cell metabolism in culture and promotes tumor development in mouse models (PMID: 24857548).
Y103S missense unknown TP53 Y103S lies within the DNA-binding domain and CCAR2, WWOX, HIPK1, and ZNF385A-interacting regions of the Tp53 protein (UniProt.org). Y103S has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
E204fs frameshift loss of function - predicted TP53 E204fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 204 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the oligomerization domain (UniProt.org), E204fs is predicted to lead to a loss of Tp53 protein function.
K320E missense unknown TP53 K320E lies within the HIPK1, CARM1 and HIPK2-interacting region of the Tp53 protein (UniProt.org). K320E demonstrates protein expression level similar to wild-type Tp53 in culture (PMID: 21232794).
S99Y missense unknown TP53 S99Y lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S99Y has been identified in the scientific literature (PMID: 11896595), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
T230P missense unknown TP53 T230P lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). T230P has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R273H missense loss of function TP53 R273H is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R273H results in decreased activation of Tp53 target gene expression, and also confers a gain of function to Tp53, resulting in aberrant transcriptional activation and increased cell migration (PMID: 22114072, PMID: 14743206).
G244D missense loss of function TP53 G244D lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G244D results in decreased Tp53 transactivation activity in reporter assays and decreased expression of the Tp53 target Gas7 in cultured cells (PMID: 9524109, PMID: 29706651).
M246K missense loss of function TP53 M246K lies within the DNA binding domain of the Tp53 protein (UniProt.org). M246K results in decreased activation of Tp53 target gene expression and increased tumor formation in zebrafish models (PMID: 15630097).
A161V missense unknown TP53 A161V lies within the DNA-binding domain of the Tp53 protein (UniProt.org). A161V does not result in decreased drug-induced apoptosis compared to wild-type Tp53 (PMID: 12726864), but has not been fully biochemically characterized and therefore, its effect on Tp53 protein function is unknown.
P152L missense loss of function TP53 P152L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). P152L results in decreased Tp53 transactivation activity and inability to suppress colony formation in cell culture (PMID: 25584008).
E171_V172insDDV insertion unknown TP53 E171_V172insDDV results in the insertion of three amino acids in the DNA-binding domain of the Tp53 protein between amino acids 171 and 172 (PMID: 15510160). E171_V172insDDV has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
E198D missense unknown TP53 E198D lies within the DNA-binding domain of the Tp53 protein (UniProt.org). E198D has been identified in sequencing studies (PMID: 28424201), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
K321R missense unknown TP53 K321R lies within the HIPK1, CARM1, and HIPK2-interacting region and the bipartite nuclear localization signal motif of the Tp53 protein (UniProt.org). K321R demonstrates binding to Daxx similar to the level of wild-type Tp53 in yeast (PMID: 15364927), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
L344Q missense unknown TP53 L344Q lies within the HIPK1, CARM1, and HIPK2-interacting region and oligomerization region of the Tp53 protein (UniProt.org). L344Q results in decreased Tp53 oligomer formation and transcriptional activity in yeast (PMID: 16007150), but has not been characterized in human cells and therefore its effect on Tp53 protein function is unknown.
V147L missense unknown TP53 V147L lies within the DNA-binding domain and CCAR2, HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). V147L has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
L137M missense unknown TP53 L137M lies within the DNA-binding domain of the Tp53 protein (UniProt.org). L137M has been identified in sequencing studies (PMID: 9349508), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
D281G missense unknown TP53 D281G lies within the DNA interaction domain of the Tp53 protein (UniProt.org). The functional effect of D281G is conflicting, as it has been reported to decrease transactivation of wild-type Tp53 targets and also confers a gain of function to Tp53, which leads to aberrant gene transcription and cell migration (PMID: 22114072).
Y234H missense loss of function TP53 Y234H lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). Y234H demonstrates a lack of Tp53 transactivation activity in cell culture (PMID: 10871862, PMID: 27533082).
P98S missense unknown TP53 P98S lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). P98S has been identified in the scientific literature (PMID: 27311873, PMID: 20404912, PMID: 18818522), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
T256K missense unknown TP53 T256K lies within the DNA-binding domain and the HIPK1, ZNF385A, AXIN1, and E4F1-interacting region of the Tp53 protein (UniProt.org). T256K has been identified in the scientific literature (PMID: 22801474), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
C275S missense loss of function - predicted TP53 C275S lies within the DNA interaction region of the Tp53 protein (UniProt.org). C275S is predicted to confer a loss of function to the Tp53 protein, as demonstrated by decreased DNA binding in cell culture (PMID: 12034820).
P190T missense unknown TP53 P190T lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P190T has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S127Y missense unknown TP53 S127Y lies within the DNA-binding domain of the Tp53 protein (PMID: 21760703). S127Y has been identified in the scientific literature (PMID: 23967324, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P322A missense unknown TP53 P322A lies within the CARM1, HIPK1, and HIPK2-interacting region of the Tp53 protein (UniProt.org). P322A has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R248Q missense loss of function TP53 R248Q is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248Q results in decreased transactivation of Tp53 targets and interference with wild-type Tp53 transactivation in cell culture, as well as increased Akt activation and enhanced tumor onset and growth in mouse models (PMID: 23538418, PMID: 16861262).
TP53 - KPNA3 fusion unknown TP53-KPNA3 results from the fusion of TP53 and KPNA3 (PMID: 27626065). TP53-KPNA3 has been identified in osteosarcoma (PMID: 27626065), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Dec 2018).
S215I missense loss of function - predicted TP53 S215I lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). S215I is predicted to confer a loss of function to the Tp53 protein, as demonstrated by the inability to transactivate Mdm2 in-vitro (PMID: 17325666).
N310H missense unknown TP53 N310H lies within the CCAR2, HIPK1, and CARM1-interacting region and bipartite nuclear localization motif of the Tp53 protein (UniProt.org). N310H has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
K305M missense unknown TP53 K305M lies within the nuclear localization signal domain of the Tp53 protein (PMID: 15510160). K305M results in a loss of Tp53 transactivation activity in a yeast assay and was associated with loss of nuclear Tp53 in a tumor sample (PMID: 20407015, PMID: 10719737), but has not been biochemically characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
P278S missense loss of function TP53 P278S lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). P278S results in the loss of Tp53 transactivation of p21, while retaining activation of Axl in cell culture, and promotes tumor growth in xenograft models (PMID: 22989750), and in mouse cells harboring the equivalent mouse variant (P275S), results in decreased activation of Tp53 target genes and reduced apoptotic response following DNA damage (PMID: 11867759).
A138T missense loss of function - predicted TP53 A138T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). A138T is predicted to confer a loss of function to the Tp53 protein as demonstrated by loss of transcription activity in a subset of Tp53-targeted genes in culture (PMID: 12725534).
R273S missense loss of function TP53 R273S is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R273S results in decreased activation of Tp53 target genes, as well as increased proliferation and resistance to apoptosis in cell culture (PMID: 23246812).
R273X missense loss of function - predicted TP53 R273X indicates a hotspot mutation resulting in an amino acid change at codon 273 of the Tp53 protein, which is predicted to result in a loss of Tp53 protein function.
L299R missense unknown TP53 L299R lies within the DNA-binding domain of the the Tp53 protein (PMID: 22713868). L299R has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R267L missense unknown TP53 R267L lies within the DNA-binding domain and HIPK1, ZNF385A, AXIN1 and E4F1-interacting region of the Tp53 protein (UniProt.org). R267L has been identified in the scientific literature (PMID: 23954467), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R249S missense loss of function TP53 R249S is a hotspot mutation within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R249S results in decreased DNA binding and transactivation activity of Tp53, and confers context-dependent transforming ability in cell culture (PMID: 20212049, PMID: 20538734).
K305T missense unknown TP53 K305T lies within the HIPK1 and CARM1-interacting region and the bipartite nuclear localization signal motif of the Tp53 protein (UniProt.org). K305T has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R175C missense no effect TP53 R175C is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). R175C retains wild-type Tp53 function in apoptosis and cell cycle assays (PMID: 9632751, PMID: 24665023).
H214Y missense unknown TP53 H214Y lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H214Y has been identified in the scientific literature (PMID: 26586531), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
V157fs frameshift loss of function - predicted TP53 V157fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 157 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to disruption of the DNA binding region and loss of the oligomerization domain (UniProt.org), V157fs is predicted to lead to a loss of Tp53 protein function.
H168Q missense unknown TP53 H168Q lies within the DNA binding domain of the Tp53 protein (UniProt.org). H168Q has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
A353V missense unknown TP53 A353V lies within the tetramerization of the Tp53 protein (PMID: 15510160). A353V has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
P177T missense loss of function TP53 P177T lies within the DNA binding domain of the Tp53 protein (UniProt.org). P177T results in a loss of Tp53 function as indicated by inability to bind DNA or activate transcription in cell culture (PMID: 21643018).
S227P missense unknown TP53 S227P lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN-interacting region of the Tp53 protein (UniProt.org). S227P has been identified in the scientific literature (PMID: 26687995, PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
V218del deletion unknown TP53 V218del results in the deletion of an amino acid in the Tp53 protein (UniProt.org). V218del has been identified in sequencing studies (PMID: 25356985, PMID: 30212483, PMID: 26454445), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
G245A missense loss of function TP53 G245A is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245A results in decreased DNA binding and reduced transactivation of p21 by Tp53, and also confers a gain-of-function to the Tp53 protein as demonstrated by transcriptional activation of SLC25A and increased tumorigenesis in mouse models (PMID: 24681808, PMID: 20589832).
R174G missense unknown TP53 R174G lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). R174G has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S215fs frameshift loss of function - predicted TP53 S215fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 215 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (UniProt.org, PMID: 21561095), S215fs is predicted to lead to a loss of Tp53 protein function.
V203M missense unknown TP53 V203M lies within the DNA binding domain and HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). V203M has been identified in sequencing studies (PMID: 16061860), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Aug 2018).
C124G missense unknown TP53 C124G lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C124G has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
R196L missense unknown TP53 R196L lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). R196L has been identified in the scientific literature (PMID: 25847421), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
A161T missense gain of function - predicted TP53 A161T lies within the DNA-binding domain of the Tp53 protein (PMID: 21232794). A161T is predicted to confer a gain of function to the Tp53 protein, as demonstrated by constitutive activation of Tp53 in cell culture (PMID: 16827139).
S90fs frameshift loss of function - predicted TP53 S90fs results in a change in the amino acid sequence of the Tp53 protein beginning at 90 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the DNA-binding domain as well as several other functional domains (UniProt.org), S90fs is predicted to lead to a loss of Tp53 protein function.
inact mut unknown loss of function TP53 inact mut indicates that this variant results in a loss of function of the Tp53 protein. However, the specific amino acid change has not been identified.
S99F missense unknown TP53 S99F lies within the CCAR2 and WWOX-interacting region of the Tp53 protein (UniProt.org). S99F does not interfere with Tp73 transactivation in a yeast assay (PMID: 12917626), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
E349fs frameshift unknown TP53 E349fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 349 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). E349fs has been identified in sequencing studies (PMID: 24140581), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
E286K missense loss of function - predicted TP53 E286K lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). E286K results in decreased transactivation activity in cultured cells (PMID: 20505364), and is therefore predicted to result in a loss of Tp53 protein function.
R282G missense unknown TP53 R282G is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R282G has been identified in the scientific literature (PMID: 25287991, PMID: 24508317, PMID: 25404506), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
F270I missense unknown TP53 F270I lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). F270I has been identified in sequencing studies (PMID: 27245685), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
I251M missense unknown TP53 I251M lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). I251M has been identified in the scientific literature (PMID: 28838384), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
Q317* nonsense loss of function - predicted TP53 Q317* results in a premature truncation of the Tp53 protein at amino acid 317 of 393 (UniProt.org). Due to the loss of the tetramerization domain (PMID: 22713868), Q317* is predicted to lead to a loss of Tp53 function.
N288D missense unknown TP53 N288D lies within the DNA-binding domain and HIPK1, ZNF385A, AXIN1 and E4F1-interacting region of the Tp53 protein (UniProt.org). N288D results in decreased Tp53 transcriptional activity in yeast (PMID: 12909720), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
R209fs frameshift loss of function - predicted TP53 R209fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 209 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of several functional domains including the oligomerization domain (UniProt.org), R209fs is predicted to lead to a loss of Tp53 protein function.
R306* nonsense loss of function - predicted TP53 R306* results in a premature truncation of the Tp53 protein at amino acid 306 of 393 within the Tp53 tetramerization domain (PMID: 22713868). Due to the loss of the majority of the tetramerization domain (UniProt.org), R306* is predicted to lead to a loss of Tp53 function.
H178R missense unknown TP53 H178R lies within the DNA-binding domain of the Tp53 protein (UniProt.org). H178R has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
L206F missense unknown TP53 L206F lies within the DNA-binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). L206F has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S241C missense unknown TP53 S241C lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). S241C results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
T125A missense loss of function - predicted TP53 T125A lies within the DNA binding domain and the interaction with HIPK1, ZNF385A, FBXO42 and AXIN1 region of the p53 protein (UniProt.org). T125A results in reduced Tp53 DNA binding ability in an in vitro assay, and a gain of function in activation of IGF-II in cell culture (PMID: 16687402, PMID: 10949925).
G262D missense unknown TP53 G262D lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G262D has been identified in the scientific literature (PMID: 25759210), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
K321E missense unknown TP53 K321E lies within the HIPK1, CARM1 and HIPK2-interacting region and the bipartite nuclear localization signal motif of the Tp53 protein (UniProt.org). K321E has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
R282fs frameshift loss of function - predicted TP53 R282fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 282 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the oligomerization domain (UniProt.org), R282fs is predicted to lead to a loss of Tp53 protein function.
K101Q missense unknown TP53 K101Q lies within the CCAR2, WWOX, HIPK1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). K101Q has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
E224D missense unknown TP53 E224D lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). E224D has been identified in sequencing studies (PMID: 24755471, PMID: 22669068, PMID: 19930417), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
G245D missense loss of function TP53 G245D is a hotspot mutation that lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). G245D results in decreased activation of Tp53 target genes (PMID: 22214764, PMID: 25634208, PMID: 27533082), and also confers a gain-of-function to Tp53 as demonstrated by aberrant interaction with ZBP-89, as well as induction of FOXM1 expression, and leads to decreased apoptosis in culture and increased tumor growth and metastasis in mouse models (PMID: 22214764, PMID: 29269868).
H179L missense loss of function - predicted TP53 H179L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). H179L is predicted to confer a loss of function to the Tp53 protein, as demonstrated by transformation in culture and promoting tumor formation and invasion in animal models (PMID: 9049183).
S116C missense loss of function - predicted TP53 S116C lies within the DNA-binding domain and HIPK1, ZNF385A, FBXO42, and AXIN1-interacting region of the Tp53 protein (UniProt.org). S116C has not been biochemically characterized, but is predicted to destabilize the Tp53 protein by computational mutagenesis (PMID: 15683227).
wild-type none no effect Wild-type TP53 indicates that no mutation has been detected within the TP53 gene.
F109Sfs*14 frameshift loss of function - predicted TP53 F109Sfs*14 indicates a shift in the reading frame starting at amino acid 109 and terminating 14 residues downstream causing a premature truncation of the 393 amino acid Tp53 protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (UniProt.org, PMID: 21561095), F109Sfs*14 is predicted to lead to a loss of Tp53 protein function.
L194R missense loss of function TP53 L194R lies within the DNA binding domain of the Tp53 protein (UniProt.org). L194R results in decreased wild-type Tp53 transactivation activity and loss of growth suppression activity, and also confers a gain of function to Tp53 resulting in aberrant activation of ASNS and hTERT in culture (PMID: 12509279, PMID: 15077194).
R337C missense loss of function TP53 R337C lies within the tetramerization domain of the Tp53 protein (PMID: 20978130). R337C results decreased tetramerization and loss of Tp53 transcriptional activity, and decreased apoptotic response to irradiation in cell culture (PMID: 19454241, PMID: 9150393).
R267Q missense unknown TP53 R267Q lies within the DNA-binding domain of the Tp53 protein (UniProt.org). The functional effect of R267Q on Tp53 is conflicting as it has been demonstrated to result in decreased Tp53 transactivation activity in some cell culture assays (PMID: 10435620), while in other assays demonstrates increased activity (PMID: 25584008), and results in decreased ability to suppress growth in cell culture (PMID: 10435620, PMID: 25584008).
F212Y missense gain of function - predicted TP53 F212Y lies within the DNA-binding domain of the Tp53 protein (PMID: 20978130). F212Y is predicted to confer a gain of function to the Tp53 protein as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
K291Q missense gain of function - predicted TP53 K291Q lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). K291Q is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
M237I missense loss of function TP53 M237I lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). M237I results in decreased Tp53 transactivation activity in cell culture (PMID: 16492679, PMID: 20080630).
T102A missense loss of function - predicted TP53 T102A lies within the DNA-binding domain and WWOX, HIPK1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). T102A is predicted to confer a loss of function to the Tp53 protein as demonstrated by disruption of the interaction with the apoptotic modulating proteins Puma and Noxa in an in vitro assay (PMID: 22446329).
L194F missense loss of function TP53 L194F lies within the DNA binding domain of the Tp53 protein (UniProt.org). L194F results in decreased Tp53 transactivation activity and decreased binding to Bcl2 in cell culture (PMID: 16443602).
I232S missense loss of function TP53 I232S lies within the DNA-binding domain Tp53 protein (PMID: 22713868). I232S results in a loss of Tp53 DNA-binding ability and transcriptional activity in cell culture (PMID: 21643018).
R342fs frameshift unknown TP53 R342fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 342 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). R342fs has been identified in sequencing studies (PMID: 22237106, PMID: 28256603), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
N30fs frameshift loss of function - predicted TP53 N30fs results in a change in the amino acid sequence of the Tp53 protein beginning at 30 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the DNA-binding domain as well as several other functional domains (UniProt.org), N30fs is predicted to lead to a loss of Tp53 protein function.
R248G missense loss of function - predicted TP53 R248G is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248G is predicted to confer a loss of function to Tp53 as demonstrated by failure to repress FOXM1 transcriptional activity in cell culture (PMID: 22919068), and retains the ability to transactivate the Tp53 target genes p21 and PCNA, and also gains the ability to activate transcription of ABCB1 (MDR-1) in cell culture (PMID: 11920959).
G154fs frameshift loss of function - predicted TP53 G154fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 154 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), G154fs is predicted to lead to a loss of Tp53 protein function.
G105C missense unknown TP53 G105C lies within the DNA-binding region of the Tp53 protein (UniProt.org). G105C has been identified in sequencing studies (PMID: 24236184), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
P72fs frameshift loss of function - predicted TP53 P72fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 72 of 393, likely resulting in premature truncation of the functional protein. Due to the loss of the DNA binding region (UniProt.org), P72fs is predicted to lead to a loss of Tp53 protein function.
K120A missense loss of function TP53 K120A lies within the DNA binding region of the Tp53 protein (UniProt.org). K120A results in impaired oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 18524770), and results in decreased DNA binding and transactivation of Tp53 targets when expressed at physiological levels in culture (PMID: 16687402).
R213L missense unknown TP53 R213L lies within the DNA-binding domain of the Tp53 protein (UniProt.org). R213L has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Dec 2018).
positive unknown unknown TP53 positive indicates the presence of the TP53 gene, mRNA, and/or protein.
R248P missense loss of function - predicted TP53 R248P is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R248P is predicted to confer a loss of function to the Tp53 protein, as demonstrated by a lack of transactivation in cell culture (PMID: 8062826).
R249W missense gain of function TP53 R249W is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R249W results in increased proliferation and colony formation in cell culture, and confers a gain of function to Tp53 in the ability to repress TIMP-3 (PMID: 23612969, PMID: 16236433).
R249G missense loss of function TP53 R249G is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R249G results in decreased activation of Tp53 target genes, as well as increased proliferation and resistance to apoptosis in cell culture (PMID: 23246812).
E287A missense loss of function - predicted TP53 E287A lies within the DNA binding region of the Tp53 protein (UniProt.org). E287A is predicted to confer a loss of function to the Tp53 protein as demonstrated by impaired oligomerization of the pro-apoptotic protein Bak by Tp53 in an in vitro assay (PMID: 18524770).
R249M missense loss of function TP53 R249M is a hotspot mutation that lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). R249M results in decreased Tp53 transcriptional activation and repression in cultured cells (PMID: 15037740, PMID: 17999388).
Y163C missense loss of function TP53 Y163C lies within the DNA binding domain of the Tp53 protein (PMID: 22713868). Y163C results in decreased transactivation of Tp53 target genes, increased cellular growth rate, and failure to induce apoptosis in cell culture (PMID: 23246812).
C275Y missense loss of function - predicted TP53 C275Y lies within the DNA-binding domain of the Tp53 protein (UniProt.org). C275Y is predicted to confer a loss of function to Tp53, as it results in decreased activation of the Tp53 target p21, and is also associated with increased glycolysis in cell culture (PMID: 28993478).
C242F missense loss of function TP53 C242F lies within a zinc-binding residue in the DNA-binding region of the Tp53 protein (UniProt.org). C242F confers of loss of function to Tp53 as demonstrated by Tp53 destabilization and decreased transactivation activity in cell culture (PMID: 25294809, PMID: 22591662), however, has been reported to demonstrate radiosensitivity similar to wild-type Tp53 (PMID: 19035295).
E339* nonsense unknown TP53 E339* results in a premature truncation of the Tp53 protein at amino acid 339 of 393 (UniProt.org). E339* has been identified in sequencing studies (PMID: 24140581, PMID: 24705251, PMID: 24997986), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
V272M missense loss of function - predicted TP53 V272M lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). V272M is predicted to confer a loss of function to the Tp53 protein, as demonstrated by loss of DNA binding and transactivation ability in cell culture (PMID: 11870884).
negative unknown loss of function TP53 negative indicates a lack of the TP53 gene, mRNA, and/or protein.
A307P missense unknown TP53 A307P lies within the CARM1-interacting region of the Tp53 protein (UniProt.org). A307P has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
C141Y missense loss of function TP53 C141Y lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C141Y results in a loss of transcription activity in a subset of Tp53-target genes and increased expression of genes downregulated by wild-type Tp53 in culture (PMID: 12725534).
P98fs frameshift loss of function - predicted TP53 P98fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 98 of 393, likely resulting in premature truncation of the functional protein. Due to the loss of the DNA binding region (UniProt.org), P98fs is predicted to lead to a loss of Tp53 protein function.
N131D missense unknown TP53 N131D lies within the DNA binding domain and the HIPK1, ZNF385A, FBXO42 and AXIN1-interacting region of the Tp53 protein (UniProt.org). N131D has been identified in sequencing studies (PMID: 24405831), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
Q192K missense unknown TP53 Q192K lies within the AXIN1-interacting region of the Tp53 protein (UniProt.org). Q192K has been identified in the scientific literature (PMID: 22982087), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Feb 2018).
T118Qfs*5 frameshift loss of function - predicted TP53 T118Qfs*5 indicates a shift in the reading frame starting at amino acid 118 and terminating 5 residues downstream causing a premature truncation of the 393 amino acid Tp53 protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), T118Qfs*5 is predicted to lead to a loss of Tp53 protein function.
K164Q missense unknown TP53 K164Q lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). K164Q has been identified in the scientific literature (PMID: 9218731), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
A159V missense loss of function TP53 A159V lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). A159V results decreased Tp53 transactivation activity and leads to reduced apoptosis relative to wild type Tp53 in cell culture (PMID: 22862161).
Q136L missense unknown TP53 Q136L lies within the DNA-binding domain and HIPK1, ZNF385A, FBXO42 and AXIN-interacting region of the Tp53 protein (UniProt.org). Q136L has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Sep 2018).
V272L missense unknown TP53 V272L lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). V272L has not been biochemically characterized in human cells, but demonstrates transcription activity similar to wild-type Tp53 in yeast (PMID: 20407015), and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
K164T missense unknown TP53 K164T lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). K164T has been identified in sequencing studies (PMID: 30123427), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
E358G missense unknown TP53 E358G lies within the HIPK1, CARM1 and HIPK2-interacting regions of the Tp53 protein (UniProt.org). E358G has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
H214R missense gain of function - predicted TP53 H214R lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). H214R results in increased IL-6 expression and colony formation compared to wild-type Tp53 in cell culture (PMID: 11920959), and is therefore predicted to confer a gain of function to Tp53.
P72R missense unknown TP53 P72R lies within the CCAR2, HRMT1L2, and WWOX-interacting region of the Tp53 protein (UniProt.org). P72R is a common Tp53 polymorphism, but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PMID: 19165225, PubMed, Nov 2018).
C176Y missense loss of function TP53 C176Y lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). C176Y results in decreased Tp53 activity (PMID: 26585234), and decreased drug-induced apoptosis in cell culture (PMID: 12726864).
TP53 - NTRK1 fusion unknown TP53-NTRK1 results from the fusion of TP53 and NTRK1 (PMID: 24445538). TP53-NTRK1 has been identified in spitzoid tumors (PMID: 24445538), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Dec 2018).
N239D missense unknown TP53 N239D lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). N239D results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore its effect on Tp53 protein function is unknown.
P223L missense unknown TP53 P223L lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). The functional effect of P223L is conflicting, as it results in similar expression of Tp53 targets, senescence, and DNA-binding compared to wild-type Tp53 in cultured cells in one study (PMID: 27911860), and decreased Tp53 transactivation activity and expression of the Tp53 target p21 at physiological temperatures in cultured cells in another study (PMID: 16741917).
E285V missense loss of function TP53 E285V lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). E285V results in decreased Tp53 transactivation activity and reduced growth suppression ability in cell culture (PMID: 25584008, PMID: 18762572).
P300H missense unknown TP53 P300H lies within the HIPK1, CCAR2, CARM1, and ZNF385A-interacting region of the Tp53 protein (UniProt.org). P300H has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P322Q missense unknown TP53 P322Q lies within the CARM1, HIPK1, and HIPK2-interacting region of the Tp53 protein (UniProt.org). P322Q has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
G244V missense unknown TP53 G244V lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). G244V results in a loss of Tp53 transactivation activity in a yeast assay (PMID: 20407015), but has not been characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
P177A missense unknown TP53 P177A lies within the DNA-binding domain of the Tp53 protein (UniProt.org). P177A has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
P301R missense unknown TP53 P301R lies within the CCAR2, HIPK1, and CARM1-interacting region of the Tp53 protein (UniProt.org). P301R has not been characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
S269R missense unknown TP53 S269R lies within the DNA-binding domain and the HIPK1, ZNF385A, AXIN1 and E4F1-interacting region of the Tp53 protein (UniProt.org). S269R has been identified in the scientific literature (PMID: 29979965), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Nov 2018).
K291E missense gain of function - predicted TP53 K291E lies within the DNA binding domain of the Tp53 protein (PMID: 20978130). K291E is predicted to confer a gain of function to the Tp53 protein, as demonstrated by increased ability to induce apoptosis in cultured cells as compared to wild-type Tp53 (PMID: 15781620).
R282del deletion loss of function - predicted TP53 R282del results in the deletion of an amino acid in the DNA-binding domain of the Tp53 protein at amino acid 282 (PMID: 22713868). R282del is predicted to confer a loss of function to the Tp53 protein as demonstrated by loss of Tp53-mediated transcriptional activation in cell culture (PMID: 14690015).
R213G missense unknown TP53 R213G lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). R213G has been identified in sequencing studies (PMID: 26319365), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
N345D missense unknown TP53 N345D lies within the HIPK1, CARM1 and HIPK2-interacting region, oligomerization region, and nuclear export signal motif of the Tp53 protein (UniProt.org). N345D results in impaired tetramerization and is transcriptionally inactive in yeast (PMID: 16007150), but has not been functionally characterized in human cells and therefore, its effect on Tp53 protein function is unknown.
K24I missense unknown TP53 K24I lies within the CCAR2 and HRMT1L2-interacting region and transcription activation region of the Tp53 protein (UniProt.org). K24I has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
A276_G279del deletion unknown TP53 A276_G279del results in the deletion of four amino acids in the DNA-interacting region of the Tp53 protein from amino acids 276 to 279 (UniProt.org). A276_G279del has not been characterized in the scientific literature and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
H179N missense loss of function TP53 H179N lies within the DNA-binding domain of the Tp53 protein (PMID: 22713868). H179N results in similar Tp53 exonuclease activity compared to wild-type, but leads to decreased DNA binding in an in vitro assay, and decreased apoptotic response to X-Ray in Drosophila expressing the corresponding variant (H159N), and decreased activation of Tp53 target genes in cultured cellls (PMID: 10778859, PMID: 19462533, PMID: 27813088).
G279V missense unknown TP53 G279V lies within the DNA-binding domain of the Tp53 protein (UniProt.org). G279V results in decreased Tp53 transcriptional activity in a yeast assay (PMID: 11429700), but has not been biochemically characterized in human cells and therefore, its effect on Tp53 function is unknown.
E171Q missense unknown TP53 E171Q lies within the DNA-binding domain of the Tp53 protein (UniProt.org). E171Q has been identified in the scientific literature (PMID: 28679771), but has not been biochemically characterized and therefore, its effect on Tp53 protein function is unknown (PubMed, Oct 2018).
G244fs frameshift loss of function - predicted TP53 G244fs results in a change in the amino acid sequence of the Tp53 protein beginning at aa 244 of 393, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the DNA binding domain and the loss of the oligomerization domain (PMID: 21561095), G244fs is predicted to lead to a loss of Tp53 protein function.
Molecular Profile Protein Effect Treatment Approaches
TP53 L330H loss of function
TP53 N131T unknown
TP53 G266V unknown
TP53 D281A loss of function - predicted
TP53 S121C gain of function - predicted
TP53 C242fs loss of function - predicted p53 Gene Therapy
TP53 R158C unknown
TP53 H193P loss of function p53 Activator p53 Gene Therapy
TP53 S240T unknown
TP53 F338Y unknown
TP53 H179Q loss of function p53 Activator p53 Gene Therapy
TP53 N200K unknown
TP53 R213fs loss of function - predicted p53 Gene Therapy
TP53 E258Q loss of function
TP53 R342* unknown
TP53 R273C loss of function p53 Activator p53 Gene Therapy
TP53 V173L loss of function
TP53 G154V unknown
TP53 P98L unknown
TP53 D259V unknown
TP53 G154R unknown
TP53 Y234C loss of function p53 Activator p53 Gene Therapy
TP53 S106T unknown
TP53 G245S loss of function p53 Activator p53 Gene Therapy
EGFR mut TP53 exon 8
TP53 exon 8 unknown
TP53 R273H TP53 P309S
TP53 P309S unknown
TP53 V272A unknown
TP53 P223R unknown
TP53 G105D unknown
TP53 G334R gain of function
TP53 G112D unknown
TP53 R335H unknown p53 Activator p53 Gene Therapy
TP53 A307T unknown
TP53 R213* loss of function - predicted p53 Gene Therapy
TP53 H193Y unknown
TP53 H168D unknown
TP53 R273W loss of function - predicted p53 Activator p53 Gene Therapy
TP53 F328S loss of function - predicted
TP53 A189T unknown
TP53 S215T unknown
TP53 R181P loss of function - predicted p53 Activator p53 Gene Therapy
TP53 T377P unknown
TP53 Y205C loss of function p53 Activator p53 Gene Therapy
TP53 T329A no effect
TP53 L265V unknown
MET del exon14 TP53 R175H
KRAS G12D TP53 R175H
TP53 R175H loss of function p53 Activator p53 Gene Therapy
TP53 T170M unknown
TP53 V203E unknown
TP53 C229R unknown
TP53 V173A loss of function - predicted p53 Activator p53 Gene Therapy
TP53 I255del unknown
PTEN mutant TP53 mutant
KRAS mutant TP53 mutant
PTEN mut RB1 mut SMAD4 mut TP53 mut
APC mut BRAF mut PIK3CA mut SMAD4 mut TP53 mut
TP53 mutant RB1 wild-type
EGFR mut TP53 mut
ALK wild-type TP53 mutant
TP53 mutant unknown
EGFR wild-type STK11 wild-type TP53 mut
RB1 mut TP53 mut
BRAF mut TP53 mut
TP53 R158P unknown
TP53 T253I unknown
TP53 S96F unknown
KRAS G13D PIK3CA E545k TP53 S241F
TP53 S241F loss of function p53 Activator p53 Gene Therapy
TP53 N239T unknown
TP53 R209Kfs*6 loss of function - predicted p53 Gene Therapy
TP53 R175X loss of function - predicted
TP53 N131K unknown
TP53 R196* loss of function - predicted p53 Gene Therapy
TP53 E294G unknown
TP53 F212V unknown
TP53 M160R unknown
TP53 R158fs loss of function - predicted p53 Gene Therapy
TP53 F113Y unknown
TP53 N131fs loss of function - predicted p53 Gene Therapy
TP53 D259G unknown
TP53 exon5 unknown
TP53 Q167L unknown
TP53 S121A gain of function - predicted
TP53 P295L unknown
TP53 P151S loss of function p53 Activator p53 Gene Therapy
TP53 R181S unknown
TP53 H179R loss of function
TP53 I195F unknown
TP53 R248L loss of function p53 Activator p53 Gene Therapy
KRAS G12R TP53 R248L
TP53 R175L loss of function p53 Activator p53 Gene Therapy
BRCA1 mut TP53 Y220C
TP53 Y220C loss of function - predicted p53 Activator p53 Gene Therapy
TP53 P72R TP53 Y220C
TP53 S96A unknown
TP53 P190R unknown
TP53 K320T loss of function - predicted
TP53 T256I unknown
TP53 A161G unknown
TP53 N239I unknown
TP53 P322R unknown
TP53 Y236C loss of function p53 Activator p53 Gene Therapy
TP53 R273* loss of function - predicted p53 Gene Therapy
KRAS G12V PIK3CA E545K TP53 R273*
BRCA1 mut TP53 E298*
TP53 E298* loss of function - predicted
TP53 H193L unknown
TP53 R280D loss of function p53 Activator p53 Gene Therapy
TP53 R335fs unknown
KRAS G12V PIK3CA E545K TP53 R335fs
TP53 S99P unknown
TP53 C277F loss of function p53 Activator p53 Gene Therapy
TP53 K319R unknown
TP53 C141R unknown
TP53 S227F unknown
TP53 F212fs loss of function - predicted p53 Gene Therapy
TP53 P142L unknown
TP53 G266E loss of function
TP53 P278L unknown
TP53 K291T gain of function - predicted
TP53 P278A unknown
TP53 G245R unknown p53 Activator p53 Gene Therapy
TP53 A276V unknown
TP53 M44fs loss of function - predicted p53 Gene Therapy
TP53 V122E unknown
TP53 L289D loss of function - predicted
TP53 P223L TP53 V274F
TP53 V274F loss of function p53 Activator p53 Gene Therapy
TP53 C124S gain of function - predicted
TP53 C242R unknown
TP53 P151L unknown
TP53 P223T unknown
TP53 P177L unknown
TP53 Y163H unknown
TP53 E339K no effect
TP53 P47S unknown
TP53 R283C loss of function
TP53 R333P unknown
TP53 D324A unknown
TP53 E286G unknown
TP53 P152fs loss of function - predicted p53 Gene Therapy
TP53 C141Afs*5 loss of function - predicted p53 Gene Therapy
TP53 Y234S unknown
TP53 S121F gain of function - predicted
TP53 F212C unknown
TP53 C242Y loss of function - predicted p53 Activator p53 Gene Therapy
TP53 C135W unknown
TP53 R175A loss of function - predicted p53 Activator p53 Gene Therapy
TP53 L308R unknown
TP53 E204G unknown
TP53 C141S unknown
TP53 G245_M246insAMC unknown
TP53 T377S unknown
TP53 G266R loss of function - predicted p53 Activator p53 Gene Therapy
TP53 over exp no effect
TP53 P219S loss of function p53 Activator p53 Gene Therapy
TP53 G245V loss of function p53 Activator p53 Gene Therapy
TP53 E171V unknown
TP53 L330R loss of function
TP53 V122M unknown
TP53 A74T unknown
TP53 D324H unknown
TP53 G105A unknown
TP53 M246A unknown
TP53 T170P unknown
TP53 R280I unknown p53 Activator p53 Gene Therapy
TP53 T211I unknown
TP53 C242S loss of function
TP53 L111Q unknown
TP53 P98R unknown
TP53 S240R loss of function
TP53 S33A unknown
TP53 I254N loss of function - predicted
TP53 E224* loss of function - predicted p53 Gene Therapy
TP53 K320R loss of function
TP53 P190A unknown
TP53 E298V unknown
TP53 S227fs loss of function - predicted p53 Gene Therapy
TP53 T211S unknown
TP53 N247D unknown
TP53 M243T unknown
TP53 I254T loss of function p53 Activator p53 Gene Therapy
TP53 R273Y unknown
TP53 H297R unknown
TP53 P98fs TP53 R175C TP53 S215G
TP53 S215G loss of function p53 Activator p53 Gene Therapy
TP53 R273P loss of function p53 Activator p53 Gene Therapy
TP53 K292I gain of function - predicted
TP53 V122fs loss of function - predicted p53 Gene Therapy
TP53 F134Y loss of function
TP53 E198* loss of function - predicted p53 Gene Therapy
TP53 P359L unknown
TP53 V147A unknown
TP53 A119P unknown
TP53 Y163* loss of function - predicted p53 Gene Therapy
TP53 A159P unknown
TP53 L344R loss of function
TP53 R158G loss of function - predicted
TP53 H168N no effect
TP53 S240I unknown p53 Activator p53 Gene Therapy
TP53 V197L loss of function - predicted
TP53 H168R loss of function p53 Activator p53 Gene Therapy
ALK wild-type TP53 H168R
TP53 P278R loss of function - predicted
TP53 K320Q loss of function
TP53 S9N unknown
TP53 S99A unknown
TP53 S366Y unknown
TP53 C135F loss of function - predicted p53 Activator p53 Gene Therapy
TP53 T140S unknown
TP53 C238Y no effect
TP53 T118fs loss of function - predicted p53 Gene Therapy
TP53 G154S unknown
TP53 A159G unknown
TP53 G154A unknown
TP53 T284A no effect
TP53 R158L loss of function - predicted p53 Activator p53 Gene Therapy
TP53 C275F unknown
TP53 D324Y unknown
TP53 G244C unknown
TP53 I195* TP53 R248Q
TP53 I195* loss of function - predicted p53 Gene Therapy
TP53 C277S gain of function - predicted
TP53 H193R loss of function - predicted
TP53 H297L unknown
TP53 R249T unknown p53 Activator p53 Gene Therapy
TP53 F338S unknown
TP53 K319E unknown
TP53 S20fs loss of function - predicted p53 Gene Therapy
TP53 H179Y loss of function p53 Activator p53 Gene Therapy
TP53 V216M loss of function - predicted
KRAS G12D PTEN loss TP53 V216M
TP53 M246R loss of function - predicted p53 Activator p53 Gene Therapy
TP53 H296Y unknown
TP53 R213Q loss of function - predicted
TP53 Y327L unknown p53 Activator p53 Gene Therapy
TP53 Q100P unknown
TP53 R280T loss of function p53 Activator p53 Gene Therapy
TP53 S241Y loss of function p53 Activator p53 Gene Therapy
TP53 R282D loss of function p53 Activator p53 Gene Therapy
TP53 H179D unknown
TP53 G117E unknown
TP53 G262R unknown
TP53 D324N unknown
TP53 P295A unknown
TP53 L114fs loss of function - predicted p53 Gene Therapy
TP53 G334W unknown
TP53 R196G loss of function - predicted p53 Activator p53 Gene Therapy
TP53 N235D loss of function p53 Activator p53 Gene Therapy
TP53 G245C loss of function p53 Activator p53 Gene Therapy
TP53 H178N unknown
TP53 P300R unknown
TP53 T155P unknown
ERBB2 amp TP53 R158H
TP53 R158H loss of function p53 Activator p53 Gene Therapy
TP53 D7A loss of function - predicted p53 Activator p53 Gene Therapy
TP53 F109L unknown
TP53 K292T gain of function - predicted
TP53 N311S unknown
TP53 R337P loss of function p53 Activator p53 Gene Therapy
TP53 T211A unknown
TP53 R175G loss of function - predicted
TP53 D228N unknown
TP53 Y107N unknown
TP53 F341C loss of function - predicted
TP53 L145Q unknown
TP53 V173M loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R290G gain of function - predicted
TP53 C135fs loss of function - predicted p53 Gene Therapy
TP53 R181C loss of function
TP53 H179P unknown
TP53 I251S unknown p53 Activator p53 Gene Therapy
TP53 G245F unknown
TP53 K292Q unknown
TP53 R283A loss of function - predicted
TP53 N310I unknown
TP53 R280A loss of function p53 Activator p53 Gene Therapy
TP53 R337H loss of function
TP53 F134L loss of function - predicted p53 Activator p53 Gene Therapy
TP53 N235Y unknown
TP53 N268I unknown
TP53 G112C unknown
TP53 S303G unknown
TP53 V157P unknown
TP53 L111fs loss of function - predicted p53 Gene Therapy
TP53 C238F loss of function - predicted
TP53 V157F loss of function
TP53 E180K loss of function p53 Activator p53 Gene Therapy
TP53 P301Q unknown
TP53 A159fs loss of function - predicted p53 Gene Therapy
TP53 P322S unknown
TP53 N310S unknown
TP53 E271K loss of function - predicted
TP53 R249K unknown p53 Activator p53 Gene Therapy
TP53 C275* loss of function p53 Gene Therapy
TP53 L344P loss of function
MET over exp TP53 dec exp
TP53 dec exp no effect
TP53 E285K loss of function
TP53 S303R unknown
TP53 E336* loss of function
TP53 P98A loss of function p53 Activator p53 Gene Therapy
TP53 E224K unknown
TP53 N131S unknown
TP53 P250L loss of function
TP53 V203L unknown
TP53 D281E loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R273L loss of function p53 Activator p53 Gene Therapy
TP53 M237V unknown
TP53 Y236F unknown
TP53 R280M loss of function
TP53 M160K unknown
TP53 C135Y loss of function
TP53 W53* loss of function - predicted p53 Gene Therapy
TP53 P177S unknown
TP53 A307S unknown
TP53 K164M loss of function - predicted
TP53 P12S unknown
TP53 L323R unknown
TP53 R110P loss of function p53 Activator p53 Gene Therapy
TP53 P82Rfs*41 loss of function - predicted p53 Gene Therapy
TP53 G108V unknown
TP53 S392fs unknown
TP53 K139M unknown
TP53 R337L loss of function p53 Activator p53 Gene Therapy
TP53 S185R unknown
TP53 K164N unknown
TP53 F341V unknown
TP53 M237_S241del unknown
TP53 R181G unknown
TP53 exon7 unknown
TP53 M246I loss of function p53 Activator p53 Gene Therapy
TP53 G154C unknown
TP53 P278H unknown
TP53 P190S loss of function p53 Activator p53 Gene Therapy
TP53 Y103* loss of function - predicted p53 Gene Therapy
MET amp TP53 del
TP53 del loss of function
KRAS G12V TP53 del
TP53 R174M unknown
BRCA1 loss TP53 loss
BRCA1 C61G TP53 loss
KRAS mut STK11 loss TP53 loss
ALK rearrange RB1 C706F TP53 loss
TP53 loss loss of function
PTEN loss TP53 loss
TP53 Q100R unknown
TP53 R282H unknown
TP53 T140I unknown
TP53 K101N unknown
TP53 L111P unknown
TP53 M246T unknown
TP53 A189D unknown
TP53 D259Y unknown
TP53 L22P unknown
TP53 C124fs loss of function - predicted p53 Gene Therapy
TP53 P190L unknown
TP53 P300A unknown
TP53 C135S loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R248E unknown p53 Activator p53 Gene Therapy
TP53 R283P unknown
TP53 L130I unknown
TP53 L130R unknown
TP53 H297P unknown
TP53 S96P unknown
TP53 S106N unknown
TP53 D259N unknown
TP53 A161P unknown
TP53 S183L unknown
TP53 K305N unknown
TP53 I195S unknown
TP53 R280K gain of function
TP53 R248W VHL inact mut
KRAS G12D PIK3CA H1047R TP53 R248W
KRAS G12C PIK3CA H1047R TP53 R248W
TP53 R248W loss of function p53 Activator p53 Gene Therapy
RB1 K240Sfs*22 TP53 R248W
TP53 R342P loss of function
TP53 K120E loss of function
TP53 V143A loss of function p53 Activator p53 Gene Therapy
TP53 L111M unknown
TP53 V172F loss of function - predicted
TP53 P151H loss of function p53 Activator p53 Gene Therapy
ALK wild-type TP53 C176F
TP53 C176F loss of function - predicted p53 Activator p53 Gene Therapy
TP53 H193Q unknown
TP53 R282Q gain of function p53 Activator p53 Gene Therapy
TP53 I50S unknown
TP53 K132Q unknown
TP53 P301fs loss of function - predicted
TP53 R282W loss of function p53 Activator p53 Gene Therapy
KRAS G12V PIK3CA Q546K TP53 R282W
TP53 Y103S unknown
TP53 E204fs loss of function - predicted p53 Gene Therapy
TP53 K320E unknown
TP53 S99Y unknown
TP53 T230P unknown
BRAF V600E PIK3CA P449T TP53 R273H
TP53 R273H loss of function p53 Activator p53 Gene Therapy
TP53 G244D loss of function
TP53 M246K loss of function
TP53 A161V unknown
TP53 P152L loss of function p53 Activator p53 Gene Therapy
TP53 E171_V172insDDV unknown
TP53 E198D unknown
TP53 K321R unknown
TP53 L344Q unknown
TP53 V147L unknown
TP53 L137M unknown
TP53 D281G unknown
TP53 Y234H loss of function p53 Activator p53 Gene Therapy
TP53 P98S unknown
TP53 T256K unknown
TP53 C275S loss of function - predicted
TP53 P190T unknown
TP53 S127Y unknown
KRAS G12D TP53 S127Y
TP53 P322A unknown
TP53 R248Q loss of function p53 Activator p53 Gene Therapy
TP53 - KPNA3 unknown
TP53 S215I loss of function - predicted p53 Activator p53 Gene Therapy
TP53 N310H unknown
TP53 K305M unknown
TP53 P278S loss of function p53 Activator p53 Gene Therapy
TP53 A138T loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R273S loss of function p53 Activator p53 Gene Therapy
TP53 R273X loss of function - predicted
TP53 L299R unknown
TP53 R267L unknown
TP53 R249S loss of function p53 Activator p53 Gene Therapy
TP53 K305T unknown
TP53 R175C no effect
TP53 H214Y unknown
KRAS mut TP53 G105C TP53 V157fs
TP53 V157fs loss of function - predicted p53 Gene Therapy
TP53 H168Q unknown
TP53 A353V unknown
ALK wild-type TP53 P177T
TP53 P177T loss of function
TP53 S227P unknown
TP53 V218del unknown
TP53 G245A loss of function p53 Activator p53 Gene Therapy
TP53 R174G unknown
TP53 S215fs loss of function - predicted p53 Gene Therapy
TP53 V203M unknown
TP53 C124G unknown
TP53 R196L unknown
TP53 A161T gain of function - predicted
PIK3CA H1047R TP53 S90fs
TP53 S90fs loss of function - predicted p53 Gene Therapy
EGFR mut TP53 inact mut
TP53 inact mut loss of function p53 Activator p53 Gene Therapy
BRCA1 inact mut TP53 inact mut
TP53 S99F unknown
TP53 E349fs unknown
TP53 E286K loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R282G unknown
TP53 F270I unknown
TP53 I251M unknown
TP53 Q317* loss of function - predicted
TP53 N288D unknown
TP53 R209fs loss of function - predicted p53 Gene Therapy
KRAS G12D PTEN dec exp TP53 R306*
TP53 R306* loss of function - predicted
TP53 H178R unknown
TP53 L206F unknown
TP53 S241C unknown
TP53 T125A loss of function - predicted
TP53 G262D unknown
TP53 K321E unknown
TP53 R282fs loss of function - predicted p53 Gene Therapy
TP53 K101Q unknown
TP53 E224D unknown
TP53 G245D loss of function p53 Activator p53 Gene Therapy
TP53 H179L loss of function - predicted p53 Activator p53 Gene Therapy
TP53 S116C loss of function - predicted
KRAS G13D PIK3CA H1047R TP53 wild-type
KRAS mut + TP53 wild-type
KRAS G12D PIK3CA H1047R TP53 wild-type
ALK R1275Q TP53 wild-type
ALK F1174L TP53 wild-type
KRAS G12V PIK3CA E545K TP53 wild-type
BRAF V600E PIK3CA H1047R TP53 wild-type
TP53 wild-type no effect
EGFR exon 19 del TP53 wild-type
BRAF V600E PTEN loss TP53 wild-type
ALK wild-type TP53 wild-type
TET2 loss TP53 wild-type
TP53 wild-type RB1 wild-type
KRAS G12D PIK3CA E545K PIK3CA H1047L TP53 wild-type
ALK amp Tp53 wild-type
TET2 inact mut TP53 wild-type
ALK mut TP53 wild-type
ALK F1245C TP53 wild-type
BRAF mut + TP53 wild-type
ALK act mut TP53 wild-type
TP53 F109Sfs*14 loss of function - predicted p53 Gene Therapy
TP53 L194R loss of function p53 Activator p53 Gene Therapy
TP53 R337C loss of function p53 Activator p53 Gene Therapy
TP53 R267Q unknown
TP53 F212Y gain of function - predicted
TP53 K291Q gain of function - predicted
TP53 M237I loss of function
TP53 T102A loss of function - predicted
TP53 L194F loss of function p53 Activator p53 Gene Therapy
TP53 I232S loss of function
TP53 R342fs unknown
MET del exon14 TP53 N30fs
TP53 N30fs loss of function - predicted p53 Gene Therapy
TP53 R248G loss of function - predicted p53 Activator p53 Gene Therapy
TP53 G154fs loss of function - predicted p53 Gene Therapy
TP53 G105C unknown
TP53 P72fs loss of function - predicted p53 Gene Therapy
TP53 K120A loss of function
TP53 R213L unknown
TP53 positive unknown
TP53 R248P loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R249W gain of function p53 Activator p53 Gene Therapy
TP53 R249G loss of function p53 Activator p53 Gene Therapy
TP53 E287A loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R249M loss of function p53 Activator p53 Gene Therapy
TP53 Y163C loss of function p53 Activator p53 Gene Therapy
TP53 C275Y loss of function - predicted
TP53 C242F loss of function
TP53 E339* unknown
TP53 V272M loss of function - predicted p53 Activator p53 Gene Therapy
TP53 negative loss of function
TP53 A307P unknown
TP53 C141Y loss of function p53 Activator p53 Gene Therapy
TP53 P98fs loss of function - predicted p53 Gene Therapy
TP53 N131D unknown
TP53 Q192K unknown
BRAF V600E TP53 Q192K
KRAS Q61L PIK3CA E542K TP53 T118Qfs*5
TP53 T118Qfs*5 loss of function - predicted p53 Gene Therapy
TP53 K164Q unknown
TP53 A159V loss of function p53 Activator p53 Gene Therapy
TP53 Q136L unknown
TP53 V272L unknown
TP53 K164T unknown
TP53 E358G unknown
TP53 H214R gain of function - predicted
TP53 P72R unknown
TP53 C176Y loss of function
TP53-NTRK1 unknown
TP53 N239D unknown
TP53 P223L unknown
TP53 E285V loss of function p53 Activator p53 Gene Therapy
TP53 P300H unknown
TP53 P322Q unknown
TP53 G244V unknown
TP53 P177A unknown
TP53 P301R unknown
TP53 S269R unknown
TP53 K291E gain of function - predicted
TP53 R282del loss of function - predicted p53 Activator p53 Gene Therapy
TP53 R213G unknown
TP53 N345D unknown
TP53 K24I unknown
TP53 A276_G279del unknown
TP53 H179N loss of function p53 Activator p53 Gene Therapy
TP53 G279V unknown
TP53 E171Q unknown
TP53 G244fs loss of function - predicted p53 Gene Therapy
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 E258Q osteosarcoma resistant Nutlin-3a Preclinical Actionable In a preclinical study, TP53 E258Q resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). 21643018
TP53 Y234C non-small cell lung carcinoma decreased response Seliciclib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 Y234C demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
TP53 Y234C ovarian carcinoma sensitive ReACp53 Preclinical Actionable In a preclinical study, ReACp53 induced cell death in human primary ovarian carcinoma cells harboring TP53 Y234C in culture (PMID: 26748848). 26748848
EGFR mut TP53 exon 8 non-small cell lung carcinoma decreased response unspecified EGFR tyrosine kinase inhibitor Clinical Study Actionable In a clinical study, EGFR-mutant non-small cell lung cancer patients with TP53 exon 8 mutations demonstrated a disease control rate (DCR) of 42% (5/12), median progression-free survival (mPFS) of 4.2 mo and median overall survival (mOS) of 16.2 mo with first-line EGFR tyrosine kinase inhibitor treatment (such as Iressa (gefitinib), Tarceva (erlotinib), Gilotrif (afatinib), or Dacomitinib), vs a DCR of 87% (97/111), mPFS of 12.5 mo, and mOS of 32.3 mo in TP53 exon 8 wild-type patients (PMID: 27780855). detail... 27780855
TP53 R273H TP53 P309S colorectal cancer sensitive Cisplatin + NSC59984 Preclinical - Cell culture Actionable In a preclinical study, the combination of Platinol (cisplatin) and NSC59984 worked synergistically to decrease viability of a colorectal cancer cell line harboring TP53 R273H and TP53 P309S in culture (PMID: 26294215). 26294215
TP53 R273H TP53 P309S colorectal cancer sensitive NSC59984 Preclinical - Cell culture Actionable In a preclinical study, treatment with NSC59984 induced Tp53 pathway signaling, degradation of mutant Tp53, and cell death in a colorectal cancer cell line harboring TP53 R273H and TP53 P309S in culture (PMID: 26294215). 26294215
TP53 R273W breast cancer resistant NSC319726 Preclinical - Cell culture Actionable In a preclinical study, NSC319726 did not inhibit tumor growth in xenograft models of breast cancer harboring TP53 R273W (PMID: 22624712). 22624712
MET del exon14 TP53 R175H histiocytic and dendritic cell cancer sensitive Crizotinib Clinical Study Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a decrease in tumor volume by more than 60% in a patient with histiocytic sarcoma harboring MET deletion exon 14 and TP53 R175H (PMID: 25971938). 25971938
KRAS G12D TP53 R175H pancreatic cancer sensitive Pimasertib + Gemcitabine Preclinical Actionable In a preclinical study, the combination of pimasertib and Gemzar (gemcitabine) inhibited tumor growth in a syngeneic mouse model of pancreatic cancer expressing KRAS G12D and TP53 R175H (PMID: 26228206). 26228206
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma conflicting Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) treatment in transgenic animal models of pancreatic ductal adenocarcinoma harboring KRAS G12D and TP53 R175H resulted in proliferation of tumor cells in interior, hypovascularized tumor regions, but inhibited proliferation in outer, vascularized tumor regions, despite inhibition of mTORC signaling in both regions (PMID: 26144316). 26144316
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma sensitive SRA737 Preclinical Actionable In a preclinical study, SRA737 (CCT245737) resulted in some decreased tumor volume in a pancreatic ductal adenocarcinoma transgenic mouse model harboring KRAS G12D and TP53 R175H when compared to control (PMID: 27167172). 27167172
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma sensitive Gemcitabine + SRA737 Preclinical Actionable In a preclinical study, Gemzar (gemcitabine) resulted in enhanced antitumor efficacy, including decreased tumor volume, when combined with SRA737 (CCT245737) in a pancreatic ductal adenocarcinoma transgenic mouse model harboring KRAS G12D and TP53 R175H (PMID: 27167172). 27167172
TP53 R175H colorectal cancer sensitive NSC59984 Preclinical - Cell culture Actionable In a preclinical study, treatment with NSC59984 resulted in increased degradation of mutant Tp53 and cell death in a colorectal cancer cell line harboring TP53 R175H in culture (PMID: 26294215). 26294215
TP53 R175H non-small cell lung carcinoma resistant Seliciclib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 R175H were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
TP53 R175H head and neck cancer sensitive ReACp53 Preclinical Actionable In a preclinical study, ReACp53 induced cell death and decreased proliferation of head and neck carcinoma cells harboring TP53 R175H in culture (PMID: 26748848). 26748848
TP53 R175H Advanced Solid Tumor sensitive Alvespimycin + Vorinostat Preclinical Actionable In a preclinical study, Alvespimycin (17-DMAG) and Zolinza (vorinostat) extended survival by 59% in mice with tumors expressing Tp53 R172H (which corresponds to R175H in the human Tp53 protein) (PMID: 26009011). 26009011
TP53 R175H breast cancer sensitive Ganetespib Preclinical Actionable In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 R175H in culture (PIMD: 26009011). 26009011
TP53 R175H breast cancer sensitive NSC319726 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells harboring TP53 R175H demonstrated increased sensitivity to NSC319726 in culture (PMID: 22624712). 22624712
TP53 R175H ovarian cancer sensitive NSC319726 Preclinical - Cell culture Actionable In a preclinical study, ovarian cancer cells harboring TP53 R175H demonstrated increased sensitivity to NSC319726-induced growth inhibition in culture and in cell line xenograft models (PMID: 22624712). 22624712
TP53 R175H ovarian clear cell adenocarcinoma decreased response DS-7423 Preclinical - Cell culture Actionable In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring TP53 S241F demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). 24504419
TP53 R175H Advanced Solid Tumor sensitive ReACp53 Preclinical Actionable In a preclinical study, treatment with ReACp53 induced cell death in primary human uterine fibroblasts expressing TP53 R175H in culture (PMID: 26748848). 26748848
PTEN mutant TP53 mutant skin cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, a skin cancer cell line harboring mutations in PTEN and TP53 demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). 25261369
PTEN mutant TP53 mutant glioblastoma multiforme sensitive Navitoclax + ONC201 Preclinical - Cell culture Actionable In a preclinical study, the combination of ONC201 (TIC10) and Navitoclax (ABT-263) increased apoptosis and worked synergistically to inhibit proliferation of a glioblastoma cell line harboring mutations in PTEN and TP53 in culture (PMID: 26474387). 26474387
KRAS mutant TP53 mutant lung adenocarcinoma predicted - sensitive unspecified PD-1 antibody Clinical Study Actionable In a clinical study, lung adenocarcinoma patients co-harboring a KRAS mutation and TP53 mutation demonstrated a greater objective response rate (35.7% vs 7.4% vs 28.6%) compared to patients with KRAS and STK11 mutations and patients with KRAS mutations only when treated with a PD-1 inhibitor (Nivolumab, n=146; Pembrolizumab, n=19) (PMID: 29773717). 29773717
KRAS mutant TP53 mutant non-small cell lung carcinoma predicted - sensitive Nivolumab Phase III Actionable In a Phase III trial, non-small cell lung carcinoma patients co-harboring a KRAS mutation and TP53 mutation demonstrated an objective response rate (ORR) of 57.1% (4/7) when treated with Opdivo (nivolumab) compared to an ORR of 0% (0/6) in patients co-harboring a KRAS mutation and STK11 mutation and an ORR of 18.2% (2/11) in patients with mutant KRAS only (PMID: 29773717; NCT01673867). 29773717
KRAS mutant TP53 mutant colorectal cancer sensitive Abemaciclib Phase I Actionable In a Phase I trial, a colorectal cancer patient co-harboring a KRAS mutation and TP53 mutation demonstrated sensitivity when treated with Abemaciclib (LY2835219), which resulted in stable disease (PMID: 27217383). 27217383
KRAS mutant TP53 mutant non-small cell lung carcinoma predicted - sensitive Pembrolizumab Phase I Actionable In a clinical study, a retrospective analysis of a Phase I trial demonstrated four non-small cell lung carcinoma (NSCLC) patients co-harboring a TP53 mutation and KRAS mutation had greater progression free survival compared to NSCLC patients harboring a single TP53 mutation or single KRAS mutation when treated with Keytruda (pembrolizumab) (PMID: 28039262). 28039262
KRAS mutant TP53 mutant colorectal cancer sensitive ABT-263 + Alpelisib + Erlotinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Mekinist (trametinib), Alpelisib (BYL719), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a KRAS mutation and TP53 mutation compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
PTEN mut RB1 mut SMAD4 mut TP53 mut skin cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, a skin cancer cell line harboring mutations in PTEN, RB1, SMAD4 and TP53 demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). 25261369
APC mut BRAF mut PIK3CA mut SMAD4 mut TP53 mut colorectal cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, a rapamycin-resistant colorectal cancer cell line harboring mutations in APC, BRAF, PIK3CA, SMAD4 and TP53 was sensitive to Sapanisertib (MLN0128) resulting in inhibition of MTORC1 signaling (PMID: 25261369). 25261369
TP53 mutant RB1 wild-type breast carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
TP53 mutant RB1 wild-type colon carcinoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). 17121911
TP53 mutant RB1 wild-type osteosarcoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of osteosarcoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). 17121911
TP53 mutant RB1 wild-type mantle cell lymphoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). 17121911
EGFR mut TP53 mut non-small cell lung carcinoma decreased response unspecified EGFR tyrosine kinase inhibitor Clinical Study Actionable In a clinical study, non-small cell lung cancer patients harboring both EGFR and TP53 mutations demonstrated a disease control rate of 70.3% (26/37) following first-line treatment with an EGFR inhibitor such as Iressa (gefitinib), Tarceva (erlotinib), Gilotrif (afatinib), or Dacomitinib, compared to a DCR of 88.2% (75/85) in TP53 wild-type, EGFR-mutant patients (PMID: 27780855). detail... 27780855
ALK wild-type TP53 mutant neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). 26438783
TP53 mutant acute myeloid leukemia predicted - sensitive Cytarabine + Venetoclax Phase Ib/II Actionable In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 30% (3/10) of patients with acute myeloid leukemia harboring TP53 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). detail...
TP53 mutant triple-receptor negative breast cancer predicted - sensitive Carboplatin + Nutlin-3 Preclinical - Cell culture Actionable In a preclinical study, Nutlin-3 and Paraplatin (carboplatin) synergistically inhibited growth in TP53 mutated triple-receptor negative breast cancer cell lines in culture and in cell line xenograft models (PMID: 26494859). 26494859
TP53 mutant ovarian clear cell adenocarcinoma decreased response DS-7423 Preclinical Actionable In a preclinical study, ovarian clear cell adenocarcinoma cell lines harboring TP53 mutations demonstrated reduced sensitivity to DS-7423 induced apoptosis in culture compared to TP53 wild-type cells (PMID: 24504419). 24504419
TP53 mutant CLL/SLL sensitive Venetoclax Guideline Actionable Venclexta (venetoclax) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). detail...
TP53 mutant non-small cell lung carcinoma sensitive CEP-8983 + Cisplatin Preclinical Actionable In a preclinical study, the combination of CEP-8983 and Platinol (cisplatin) worked synergistically to induce cell death in non-small cell lung cancer cell lines in culture, irrespective of TP53 status (PMID: 23428903). 23428903
TP53 mutant Advanced Solid Tumor sensitive Adavosertib Phase I Actionable In a retrospective analysis of a Phase I trial, MK-1775 combined with a chemotherapy resulted in a 21% (4/19) response rate in advanced solid tumor patients harboring a TP53 mutation and in those without a TP53 mutation, a 12% (4/33) response rate was observed (PMID: 27601554). 27601554
TP53 mutant colorectal cancer sensitive Prodigiosin Preclinical - Cell line xenograft Actionable In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 26759239). 26759239
TP53 mutant head and neck squamous cell carcinoma sensitive AZD7762 + Cisplatin Preclinical Actionable In a preclinical study, the treatment of a head and neck squamous cell carcinoma cell line with mutant TP53 (C176F and A161S) with AZD7762, a pan Chk1/2 inhibitor, sensitizes the cells to Platinol (cisplatin) (PMID: 23839309). 23839309
TP53 mutant leukemia decreased response RG7112 Phase I Actionable In a Phase I clinical trial, the majority of 19 leukemia patients with identified TP53 mutations did not demonstrate response to treatment with RG7112, with 2 acute myeloid leukemia patients harboring TP53 mutations showing clinical activity, but not improvement, and 1 sCLL/CLL patient achieving stable disease (PMID: 26459177). 26459177
TP53 mutant hypopharynx cancer predicted - sensitive EGFR antibody + ERBB3 antibody + IGF-1R antibody Preclinical - Cell culture Actionable In a preclinical study, combination of an unspecified EGFR antibody, an unspecified Erbb3 (Her3) antibody, and an unspecified Igf-1r antibody resulted in potent inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
TP53 mutant neuroblastoma resistant MI-63 Preclinical Actionable In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to MI-63 mediated growth inhibition (PMID: 21725357). 21725357
TP53 mutant ovarian cancer no benefit Nutlin-3a Preclinical Actionable In a preclinical study, treatment with Nutlin-3 had little effect on growth of ovarian cancer cells with TP53 mutations in culture (PMID: 25964101). 25964101
TP53 mutant sarcoma sensitive Pazopanib Clinical Study Actionable In a retrospective study, advanced sarcoma patients with TP53 mutations displayed improved progression-free survival (208 days versus 136 days) relative to patients with wild-type TP53 when treated with Votrient (pazopanib) (PMID: 26646755). 26646755
TP53 mutant Advanced Solid Tumor resistant AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 did not inhibit growth of human tumor cell lines harboring TP53 mutations in culture (PMID: 25567130). 25567130
TP53 mutant fibrous histiocytoma predicted - sensitive GDC-0575 + Gemcitabine Preclinical - Pdx Actionable In a preclinical study, GDC-0575 and Gemzar (gemcitabine) combination treatment inhibited tumor growth, prolonged progression-free survival in patient-derived xenogrft (PDX) models of undifferentiated pleomorphic sarcoma (fibrous histiocytoma) (PMID: 29409053). 29409053
TP53 mutant hypopharynx cancer predicted - sensitive unspecified EGFR antibody + unspecified ERBB3 antibody Preclinical - Cell culture Actionable In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Erbb3 (Her3) antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
TP53 mutant hypopharynx cancer resistant unspecified EGFR antibody Preclinical - Cell culture Actionable In a preclinical study, combination of two unspecified EGFR antibodies targeting nonoverlapping epitopes of Egfr did not inhibit proliferation of Tp53 mutated hypopharyngeal carcinoma cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
TP53 mutant triple-receptor negative breast cancer predicted - sensitive GDC-0425 + Gemcitabine Phase I Actionable In a Phase I trial, treatment with GDC-0425 followed by Gemzar (gemcitabine) resulted in a partial response in a patient with triple-receptor negative breast cancer harboring a TP53 mutation (PMID: 27815358). 27815358
TP53 mutant ovarian cancer predicted - sensitive MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in an overall response rate of 43% (9/21), a median progression-free survival of 5.3 months and a median overall survival of 12.6 months in ovarian cancer patients harboring TP53 mutations (PMID: 27998224). 27998224
TP53 mutant osteosarcoma not applicable N/A Guideline Risk Factor Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing osteosarcoma (NCCN.org). detail...
TP53 mutant CLL/SLL sensitive GDC-0199 + Rituximab Guideline Actionable Venclexta (venetoclax) combined with Rituxan (rituximab) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). detail...
TP53 mutant Advanced Solid Tumor sensitive Bevacizumab Clinical Study Actionable In a retrospective study, Avastin (bevacizumab) treatment was associated with increased progression-free survival in cancer patients carrying TP53 mutations (PMID: 23670029). 23670029
TP53 mutant Advanced Solid Tumor sensitive Bevacizumab Clinical Study Actionable In a clinical study, 106 advanced solid tumor patients harboring a TP53 mutation demonstrated a greater sensitivity to VEGF/VEGFR inhibitors, such as Avastin (bevacizumab), when compared to 82 treated patients harboring TP53 wild-type, resulting in improved rates of SD, PR, and CR, better time-to-treatment failure, and overall survival (PMID: 27466356). 27466356
TP53 mutant Advanced Solid Tumor sensitive CTX-1 Preclinical Actionable In a preclinical study, CTX-1 induced increased Tp53 protein levels and cell death in human tumor cell lines with mutant Tp53 in culture (PMID: 26883273). 26883273
TP53 mutant glioblastoma multiforme sensitive AZD1390 Preclinical - Cell culture Actionable In a preclinical study, TP53 mutant glioblastoma cells demonstrated increased sensitivity to radiosensitization by AZD1390 treatment compared to TP53 wild-type cells in culture (Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A104). detail...
TP53 mutant sarcoma predicted - sensitive GDC-0575 + Gemcitabine Clinical Study Actionable In a preclinical study, GDC-0575 and Gemzar (gemcitabine) combination treatment resulted in prolonged tumor response in 2 soft tissue sarcoma patients harboring TP53 mutations, and no response in a patient with TP53 wild-type tumor (PMID: 29409053). 29409053
TP53 mutant CLL/SLL sensitive Ibrutinib Guideline Actionable Imbruvica (ibrutinib) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). detail...
TP53 mutant sarcoma sensitive Pazopanib + Vorinostat Phase I Actionable In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). 25669829
TP53 mutant pharynx squamous cell carcinoma sensitive AZD6738 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a pharynx squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). 28062704
TP53 mutant glioblastoma multiforme sensitive Adavosertib Preclinical - Pdx Actionable In a preclinical study, treatment with MK-1775 decreased CDK1 phosphorylation and reduced tumor growth in patient-derived xenograft models of glioblastoma multiforme that harbor TP53 mutations (PMID: 27196784). 27196784
TP53 mutant ovarian serous carcinoma sensitive thioureidobutyronitrile Preclinical - Cell culture Actionable In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment decreased mutant Tp53 level, resulted in apoptosis of ovarian serous carcinoma cells harboring TP53 mutations in culture (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). detail...
TP53 mutant hypopharynx cancer predicted - sensitive unspecified EGFR antibody + unspecified IGF-1R antibody Preclinical - Cell culture Actionable In a preclinical study, combination of an unspecified EGFR antibody and an unspecified Igf-1r antibody resulted in inhibition of survival in TP53 mutated hypopharyngeal carcinoma cancer cells that developed Erbitux (cetuximab) resistance in culture (PMID: 27196767). 27196767
TP53 mutant colorectal cancer predicted - sensitive NSC59984 Preclinical - Cell line xenograft Actionable In a preclinical study, NSC59984 treatment resulted in increased Tp53 signaling and cell death in colorectal cancer cell lines harboring TP53 mutations, and inhibited tumor growth in TP53-mutant cell line colorectal cancer xenograft models (PMID: 26294215). 26294215
TP53 mutant CLL/SLL sensitive Idelalisib + Rituximab Guideline Actionable Zydelig (idelalisib) combined with Rituxan (rituximab) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org). detail...
TP53 mutant breast carcinoma predicted - sensitive Camptothecin + CHIR-124 Preclinical - Cell culture Actionable In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant breast carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). 17255282
TP53 mutant neuroblastoma resistant Nutlin-3a Preclinical Actionable In a preclinical study, neuroblastoma cell lines harboring TP53 mutant were resistant to nutlin-3 mediated growth inhibition (PMID: 21725357). 21725357
TP53 mutant head and neck squamous cell carcinoma predicted - sensitive Buparlisib + Paclitaxel Phase II Actionable In a Phase II (BERIL-1) trial, Buparlisib (BKM120) and Taxol (paclitaxel) combination treatment resulted in improved overall survival (HR=0.52) and prolonged progression-free survival (HR=0.45) in head and neck squamous cell carcinoma patients harboring TP53 mutations compared to TP53 wild-type patients (PMID: 29490986; NCT01852292). 29490986
TP53 mutant tongue squamous cell carcinoma sensitive AZD6738 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a tongue squamous cell carcinoma cell line harboring a TP53 mutation in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). 28062704
TP53 mutant breast cancer sensitive PK11007 Preclinical - Cell culture Actionable In a preclinical study, TP53-mutated breast cancer cell lines demonstrated increased sensitivity to PK11007 compared to TP53-wild type cells in culture, regardless of Esr1 and Erbb2 (Her2) status (J Clin Oncol 35, 2017 (suppl; abstr e14099)). detail...
TP53 mutant medulloblastoma decreased response JQ1 Preclinical Actionable In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). 24231268
TP53 mutant chronic lymphocytic leukemia predicted - sensitive Ibrutinib + Venetoclax Phase II Actionable In a Phase II trial, Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy resulted in a response rate of 100% (14/14, 9 complete response, 5 partial response) in relapsed or refractory chronic lymphocytic leukemia (CLL) patients, and a response rate of 100% (16/16, 9 complete response, 7 partial response) in untreated patients with high-risk features including del 17p, TP53 mutations, and del 11q (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 429; NCT02756897). detail...
TP53 mutant non-small cell lung carcinoma predicted - sensitive Pembrolizumab Phase I Actionable In a clinical study, a retrospective analysis of a Phase I trial demonstrated non-small cell lung carcinoma (NSCLC) patients harboring either a TP53 mutation (n=15) or KRAS mutation (n=8) had greater progression free survival compared to NSCLC patients harboring wild-type TP53 or KRAS (n=15) (14.5mo vs 14.7mo vs 3.5mo, respectively) when treated with Keytruda (pembrolizumab) (PMID: 28039262). 28039262
TP53 mutant colorectal cancer sensitive Bevacizumab Phase III Actionable In a Phase III trial, Avastin (bevacizumab), in combination with chemotherapy, provided a significant survival benefit in patients with colorectal cancers regardless of mutational status in KRAS, BRAF, and TP53 (PMID: 17145525). 17145525
TP53 mutant colorectal cancer sensitive PD0166285 Preclinical Actionable In a preclinical study, PD0166285 sensitizes colorectal cancer cells with TP53 mutation to radiation induced cell death (PMID: 11719452). 11719452
TP53 mutant chronic lymphocytic leukemia predicted - sensitive Duvelisib Phase I Actionable In a Phase I trial, Copiktra (duvelisib) treatment inhibited Akt phosphorylation, resulted in complete response in 2% (1/49), partial response in 53% (26/49), and stable disease in 43% (21/49) of chronic lymphocytic leukemia patients, of which 49% (23/47) carried TP53 mutations (Blood 124 (21): 3334). detail...
TP53 mutant Advanced Solid Tumor sensitive Pazopanib + Vorinostat Phase I Actionable In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) improved progression-free survival and overall survival in advanced solid tumor patients harboring TP53 hotspot mutations, and resulted in an increased stable disease rate of 45% (5/11), compared to a stable disease rate of 16% (4/25) in patients without detected TP53 mutations (PMID: 25669829). 25669829
TP53 mutant myelodysplastic syndrome not applicable N/A Guideline Prognostic TP53 mutations except P47S and P72R are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
TP53 mutant glioblastoma multiforme sensitive MK-1775 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of MK-1775 and radiation therapy synergized to inhibit tumor growth in a human glioblastoma multiforme cell line xenograft model harboring mutant TP53 (PMID: 21992793). 21992793
TP53 mutant triple-receptor negative breast cancer predicted - sensitive Doxorubicin + Seliciclib Preclinical - Cell line xenograft Actionable In a preclinical study, sequential administration of Roscovotine (seliciclib) followed by Adriamycin (doxorubicin) synergistically induced apoptosis in TP53-mutant triple-receptor negative breast cancer cell lines in culture, and inhibited tumor growth, prolonged survival in cell line xenograft models (PMID: 26826118). 26826118
TP53 mutant colorectal cancer sensitive Pazopanib + Vorinostat Phase I Actionable In a Phase I trial, the combination of Votrient (pazopanib) and Zolinza (vorinostat) resulted in improved progression-free survival and overall survival in metastatic sarcoma and colorectal cancer patients harboring TP53 hotspot mutations, and resulted in a stable disease rate of 83% (5/6), compared to a stable disease rate of 9% (1/11) in patients without detected TP53 mutations (PMID: 25669829). 25669829
TP53 mutant ovarian cancer sensitive Nutlin-3 + Etoposide Preclinical Actionable In a preclinical study, Nutlin-3 and etoposide worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). 25964101
TP53 mutant essential thrombocythemia not applicable N/A Guideline Prognostic TP53 mutations are associated with inferior leukemia-free survival in patients with essential thrombocythemia (NCCN.org). detail...
TP53 mutant essential thrombocythemia not applicable N/A Guideline Prognostic The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SF3B1, EZH2, or TP53 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org). detail...
TP53 mutant colon carcinoma predicted - sensitive Camptothecin + CHIR-124 Preclinical - Cell culture Actionable In a preclinical study, the combination of Camptothecin and CHIR-124 demonstrated synergy in TP53-mutant colon carcinoma cell lines in culture, resulting in increased growth inhibition (PMID: 17255282). 17255282
TP53 mutant neuroblastoma resistant GSK2830371 Preclinical Actionable In a preclinical study, neuroblastoma cell lines harboring TP53 mutations were resistant to GSK2830371 induced growth inhibition in culture (PMID: 25658463). 25658463
EGFR wild-type STK11 wild-type TP53 mut non-small cell lung carcinoma predicted - sensitive Nivolumab Clinical Study Actionable In a retrospective analysis, a genomic profile consisted of mutant TP53, wild-type STK11 and EGFR is associated with increased PD-L1 expression and improved progression-free survival in Opdivo (nivolumab)-treated non-small cell lung cancer patients (PMID: 29764856). 29764856
EGFR wild-type STK11 wild-type TP53 mut non-small cell lung carcinoma predicted - sensitive Pembrolizumab Clinical Study Actionable In a retrospective analysis, a genomic profile consisted of mutant TP53, wild-type STK11 and EGFR is associated with increased PD-L1 expression and improved progression-free survival in Keytruda (pembrolizumab)-treated non-small cell lung cancer patients (PMID: 29764856). 29764856
RB1 mut TP53 mut prostate carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of prostate carcinoma cell lines harboring Tp53 and Rb1 mutations in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
RB1 mut TP53 mut cervical cancer sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of cervical carcinoma cell lines harboring Tp53 and Rb1 mutations (PMID: 17121911). 17121911
RB1 mut TP53 mut breast carcinoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring TP53 and RB1 mutations in culture (PMID: 17121911). 17121911
BRAF mut TP53 mut colorectal cancer sensitive ABT-263 + Alpelisib + Dabrafenib + Erlotinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
KRAS G13D PIK3CA E545k TP53 S241F colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, but did not induce apoptosis in colorectal cancer cells harboring KRAS G13D, PIK3CA E545K, and TP53 S241F in culture (PMID: 26272063). 26272063
TP53 S241F ovarian cancer sensitive Ganetespib Preclinical Actionable In a preclinical study, Ganetespib inhibited growth of human ovarian cancer cells harboring TP53 S241F in culture (PMID: 26009011). 26009011
TP53 S241F ovarian clear cell adenocarcinoma decreased response DS-7423 Preclinical - Cell culture Actionable In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring TP53 S241F demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). 24504419
TP53 S241F lung small cell carcinoma sensitive APR-246 Preclinical - Cell line xenograft Actionable In a preclinical study, APR-246 demonstrated efficacy in xenograft models of small cell lung cancer harboring TP53 S241F (PMID: 21415220). 21415220
KRAS G12R TP53 R248L lung adenocarcinoma sensitive Dasatinib + Demcizumab Preclinical - Pdx Actionable In a preclinical study, combination of Sprycel (dasatinib) and Demcizumab (OMP-21M18) treatment resulted in durable tumor inhibition in patient-derived animal models of lung adenocarcinoma harboring KRAS G12R and TP53 R248L (PMID: 26855149). 26855149
TP53 R175L lung large cell carcinoma sensitive NSC319726 Preclinical - Cell culture Actionable In a preclinical study, lung large cell carcinoma cells harboring TP53 R175L demonstrated increased sensitivity to NSC319726 in culture (PMID: 22624712). 22624712
TP53 R175L colorectal cancer sensitive NSC59984 Preclinical - Cell culture Actionable In a preclinical study, treatment with NSC59984 resulted in increased degradation of mutant Tp53 and cell death in a colorectal cancer cell line harboring TP53 R175L in culture (PMID: 26294215). 26294215
BRCA1 mut TP53 Y220C ovarian cancer sensitive Carboplatin + VX-970 Phase I Actionable In a Phase I trial, VX-970 and Paraplatin (carboplatin) combination treatment resulted in partial response for 6 months in a PARP inhibitor-resistant ovarian cancer patient harboring a germline BRCA1 mutation and TP53 Y220C (J Clin Oncol 34, 2016 (suppl; abstr 2504)). detail...
TP53 Y220C non-small cell lung carcinoma resistant Seliciclib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 Y220C were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
TP53 Y220C hepatocellular carcinoma sensitive CP-31398 Preclinical - Cell culture Actionable In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 Y220C in culture (PMID: 26250460). 26250460
TP53 P72R TP53 Y220C breast cancer no benefit Epirubicin + Cyclophosphamide Phase I Actionable In a Phase I clinical trial, a breast cancer patient carrying TP53 P72R and Y220C mutations demonstrated incomplete response to treatment with an Ellence (epirubicin)-Cytoxan (cyclophosphamide) combination regimen (PMID: 17388661). 17388661
KRAS G12V PIK3CA E545K TP53 R273* colorectal cancer resistant BEZ235 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K, and TP53 R273* did not respond to BEZ235 treatment (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 R273* colorectal cancer resistant Selumetinib Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K, and TP53 R273* did not respond to Selumetinib (AZD6244) treatment (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 R273* colorectal cancer no benefit Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment did not improve tumor growth stabilization compared to single agent in patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K and TP53 R273* (PMID: 26272063). 26272063
BRCA1 mut TP53 E298* ovarian cancer predicted - sensitive MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in partial response in an ovarian cancer patient harboring TP53 E298* and mutations in BRCA1 (PMID: 27998224). 27998224
KRAS G12V PIK3CA E545K TP53 R335fs colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K, and TP53 R335fs (PMID: 26272063). 26272063
TP53 P223L TP53 V274F prostate cancer resistant Ganetespib Preclinical Actionable In a preclinical study, Ganetespib inhibited growth of human prostate cancer cells harboring TP53 P223L and V274F in culture (PMID: 26009011). 26009011
TP53 Y163H ovarian cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 Y163H in culture (PMID: 27179933). 27179933
TP53 over exp ovarian cancer predicted - sensitive p53:264-272 vaccine Phase I Actionable In a Phase I trial, the HLA-A2 p53:264-272 vaccine demonstrated safety and preliminary efficacy in patients with TP53 overexpressing ovarian cancer, resulting in a progression-free survival of 5.5 months and an overall survival of 40.4 months (PMID: 21927947). 21927947
TP53 L111Q ovarian cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 L111Q in culture (PMID: 27179933). 27179933
TP53 P98fs TP53 R175C TP53 S215G ovarian cancer predicted - resistant MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in disease progression in an ovarian cancer patient harboring TP53 P98fs, R175C, and S215G (PMID: 27998224). 27998224
TP53 S215G non-small cell lung carcinoma resistant Seliciclib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 S215G were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
TP53 Y163* ovarian cancer predicted - sensitive MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in partial response in an ovarian cancer patient harboring TP53 Y163* (PMID: 27998224). 27998224
TP53 R158G non-small cell lung carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human non-small cell lung carcinoma cells harboring TP53 R138G in culture (PMID: 21325073, PMID: 23980093). 21325073 23980093
ALK wild-type TP53 H168R neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783). 26438783
TP53 P278R ovarian cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 P278R in culture (PMID: 27179933). 27179933
TP53 I195* TP53 R248Q ovarian carcinoma sensitive ReACp53 Preclinical Actionable In a preclinical study, ReACp53 induced cell death and decreased proliferation of human primary ovarian carcinoma cells harboring both TP53 I195* and TP53 R248Q in culture (PMID: 26748848). 26748848
KRAS G12D PTEN loss TP53 V216M colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12D, PTEN loss, and TP53 V216M (PMID: 26272063). 26272063
TP53 Y327L ovarian carcinoma sensitive ReACp53 Preclinical Actionable In a preclinical study, ReACp53 induced cell death in human primary ovarian carcinoma cells harboring TP53 Y327L in culture (PMID: 26748848). 26748848
ERBB2 amp TP53 R158H gastric adenocarcinoma predicted - resistant AMG 337 Clinical Study Actionable In a clinical case study, a patient with gastric adenocarcinoma containing amplification of ERBB2 (HER2) and a TP53 R158H mutation progressed and developed metastases while being treated with AMG 337 (PMID: 26432108). 26432108
TP53 V173M acute myeloid leukemia predicted - sensitive APR-246 Phase I Actionable In a Phase I clinical trial, APR-246 demonstrated safety and preliminary clinical activity in patients with hematological cancers, including an acute myeloid leukemia patient harboring TP53 V173M that achieved a decrease in bone marrow blast percentage from 46% to 26% (PMID: 22965953). 22965953
TP53 C238F fallopian tube cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived fallopian tube cancer cells harboring TP53 C238F in culture (PMID: 27179933). 27179933
MET over exp TP53 dec exp stomach carcinoma sensitive EMD 1214063 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, shRNA knock-down of Tp53 in Met over-expressing gastric carcinoma cells enhanced sensitivity to the combination of EMD 1214063 and radiation in culture (PMID: 26358474). 26358474
TP53 P98A non-small cell lung carcinoma decreased response Seliciclib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 P98A demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
TP53 R273L lung small cell carcinoma sensitive APR-246 Preclinical - Cell line xenograft Actionable In a preclinical study, APR-246 demonstrated efficacy in cell line xenograft models of small cell lung cancer harboring TP53 R273L (PMID: 21415220). 21415220
TP53 R280M osteosarcoma resistant Nutlin-3a Preclinical Actionable In a preclinical study, TP53 R280M resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). 21643018
TP53 C135Y peritoneum cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived peritoneum cancer cells harboring TP53 C135Y in culture (PMID: 27179933). 27179933
MET amp TP53 del breast cancer sensitive Crizotinib Preclinical Actionable In a preclinical study, Xalkori (crizotinib) treatment resulted in complete tumor regression in transplant models of TP53-null-luminal breast cancer harboring MET amplification (PMID: 27149990). 27149990
TP53 del ovarian cancer sensitive Nutlin-3 + Etoposide Preclinical Actionable In a preclinical study, Nutlin-3 and etoposide worked cooperatively to induce apoptosis and decrease growth of ovarian cancer cells with TP53 deletion in culture (PMID: 25964101). 25964101
TP53 del colorectal cancer predicted - sensitive TC-A2317 Preclinical - Cell culture Actionable In a preclinical study, MK-8745 treatment resulted in polyploidy in TP53-null colorectal cancer cells in culture (PMID: 22293494). 22293494
TP53 del ovarian cancer no benefit Nutlin-3a Preclinical Actionable In a preclinical study, treatment with Nutlin-3 had little effect on growth of ovarian cancer cells with deletion of TP53 in culture (PMID: 25964101). 25964101
TP53 del ovarian clear cell carcinoma predicted - sensitive thioureidobutyronitrile Preclinical - Cell line xenograft Actionable In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in Tp53-independent increase of Cdkn1a expression and apoptosis of ovarian clear cell carcinoma cells harboring TP53 deletion in culture and in cell line xenograft models (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). detail...
TP53 del colorectal cancer predicted - sensitive Doxorubicin + Seliciclib Preclinical - Cell culture Actionable In a preclinical study, sequential administration of Roscovotine (seliciclib) followed by Adriamycin (doxorubicin) synergistically induced apoptosis in TP53-null colorectal cancer cells in culture (PMID: 26826118). 26826118
TP53 del ovarian cancer sensitive Nutlin-3 + Cisplatin Preclinical Actionable In a preclinical study, Nutlin-3 and cisplatin worked cooperatively to induce apoptosis and decrease growth of ovarian cancer cells with TP53 deletion in culture (PMID: 25964101). 25964101
KRAS G12V TP53 del lung cancer resistant 7RH Preclinical Actionable In a preclinical study, 7RH treatment had no effect on tumor cell apoptosis in KRAS G12V-driven animal models of lung cancer with TP53 knockout background (PMID: 26855149). 26855149
KRAS G12V TP53 del lung cancer sensitive 7RH + LY411575 Preclinical Actionable In a preclinical study, 7RH and LY411575 combination treatment induced apoptosis in KRAS G12V-driven animal models of lung cancer with TP53 knockout background (PMID: 26855149). 26855149
BRCA1 loss TP53 loss breast cancer sensitive AZD2461 Preclinical Actionable In a preclinical study, a breast cancer model lacking both BRCA1 and TP53 demonstrated sensitivity to treatment with AZD2461, which resulted in decreased tumor volume (PMID: 27550455). 27550455
BRCA1 C61G TP53 loss breast cancer decreased response Olaparib Preclinical Actionable In a preclinical study, mouse breast cancer models harboring BRCA1 C61G with conditional loss of Tp53 had a decreased response to Lynparza (olaparib) compared to models with conditional loss of Brca1 and Tp53 (PMID: 22172724). 22172724
KRAS mut STK11 loss TP53 loss non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring KRAS mutation, STK11 and TP53 loss demonstrated increased sensitivity to MK-1775 and Platinol (cisplatin) combination treatment in culture compared to isogenic cell lines expressing wild-type Tp53 or Stk11 (PMID: 28652249). 28652249
ALK rearrange RB1 C706F TP53 loss lung small cell carcinoma predicted - resistant Lorlatinib Clinical Study Actionable In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). 28285684
TP53 loss colon cancer sensitive CHIR-124 + SN-38 Preclinical - Cell culture Actionable In a preclinical study, a colon cancer cell line deficient in TP53 demonstrated increased sensitivity to sequential treatment with SN-38 and CHIR-124 compared to cells with wild-type TP53, resulting in increased apoptosis and micronucleation in culture (PMID: 17255282). 17255282
TP53 loss pancreatic cancer sensitive MK-1775 + Gemcitabine Preclinical - Pdx Actionable In a preclinical study, the combination of MK-1775 and Gemzar (gemcitabine) inhibited Wee1 expression, Cdc2 phosphorylation, and tumor growth in several patient-derived xenograft models of pancreatic cancer harboring TP53 mutations (PMID: 21389100). 21389100
TP53 loss acute myeloid leukemia resistant ALRN-6924 Preclinical - Cell culture Actionable In a preclinical study, ALRN-6924 did not inhibit the growth of TP53-null acute myeloid leukemia cells in culture (PMID: 29643228). 29643228
TP53 loss colorectal cancer sensitive Prodigiosin Preclinical Actionable In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 loss in culture (PMID: 26759239). 26759239
TP53 loss colorectal cancer predicted - sensitive Ad5CMV-p53 gene Preclinical Actionable In a preclinical study, Ad5CMV-p53 gene therapy suppressed growth of allograft colorectal cancer in rat models (PMID: 15608394). 15608394
TP53 loss glioblastoma multiforme sensitive BLZ945 Preclinical Actionable In a preclinical study, treatment with BLZ945 demonstrated some efficacy, specifically a 56% tumor reduction, in transgenic mouse models of glioblastoma with a loss of TP53 (PMID: 27199435). 27199435
TP53 loss Advanced Solid Tumor sensitive Adavosertib Preclinical Actionable In a preclinical study, tumor cell lines carrying deficient TP53 were sensitized to DNA-damaging agents upon MK-1775 administration (PMID: 19887545). 19887545
TP53 loss CLL/SLL sensitive GDC-0199 + Rituximab Guideline Actionable Venclexta (venetoclax) combined with Rituxan (rituximab) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss colon carcinoma sensitive SP600125 Preclinical Actionable In a preclinical study, SP600125 induced cell death in colon carcinoma cells deficient for p53 (PMID: 22438244). 22438244
TP53 loss colon carcinoma sensitive MPI-0479605 Preclinical Actionable In a preclinical study the TTK (MPS1) inhibitor, MPI-0479605, inhibited cell cycle progression of colon carcinoma cells deficient for Tp53 with equivalent efficacy to cells with wild-type Tp53 (PMID: 21980130). 21980130
TP53 loss colorectal cancer sensitive PHA-680632 + Radiotherapy Preclinical - Pdx Actionable In a preclinical study, PHA-680632 synergized with radiotherapy to decrease tumor growth in Pdx models deficient in Tp53 (PMID: 18026198). 18026198
TP53 loss colorectal cancer sensitive AZD6738 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AZD6738 increased sensitivity to radiotherapy in colorectal cancer xenograft models harboring a loss of TP53, resulting in a greater delay of tumor growth compared to radiation alone and an improved survival compared to control or either agent alone (PMID: 28062704). 28062704
TP53 loss colon cancer decreased response CPUY201112 Preclinical Actionable In a preclinical study, colon cancer cells lacking TP53 had a decreased response to CPUY201112 in culture, when compared to colon cancer cells with wild-type TP53 (PMID: 26743233). 26743233
TP53 loss Advanced Solid Tumor decreased response CTX-1 Preclinical Actionable In a preclinical study, CTX-1 induced cell death in TP53-deficient human tumor cell lines in culture, but had a greater effect on cell lines with wild-type TP53 compared to isogenic cell lines with TP53 loss (PMID: 26883273). 26883273
TP53 loss CLL/SLL sensitive Venetoclax Guideline Actionable Venclexta (venetoclax) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss thymoma predicted - resistant Selinexor Preclinical - Cell culture Actionable In a preclinical study, a thymoma cell line with TP53 loss demonstrated primary resistance to Selinexor (KPT-330) in culture, and reconstitution of TP53 expression resulted in increased Selinexor sensitivity (PMID: 28819023). 28819023
TP53 loss CLL/SLL sensitive Ibrutinib Guideline Actionable Imbruvica (ibrutinib) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss lung cancer resistant AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 did not enhance radiation-induced cytotoxicity in TP53-null lung cancer cells in culture and in cell line xenograft models (PMID: 26162687). 26162687
TP53 loss CLL/SLL sensitive Idelalisib + Rituximab Guideline Actionable Zydelig (idelalisib) combined with Rituxan (rituximab) is indicated in the guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss lung cancer resistant AMG 232 Preclinical - Cell culture Actionable In a preclinical study, TP53-null lung cancer cells were resistant to AMG 232 induced growth inhibition in culture (PMID: 26162687). 26162687
TP53 loss osteosarcoma decreased response CPUY201112 Preclinical Actionable In a preclinical study, an osteosarcoma cell line lacking TP53 demonstrated a decreased response to CPUY201112 in culture, when compared to osteosarcoma cells with wild-type TP53 (PMID: 26743233). 26743233
TP53 loss ovarian cancer sensitive LB-100 + Cisplatin Preclinical Actionable In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in cisplatin-resistant ovarian cancer cells with TP53 loss in culture and in xenograft models (PMID: 25376608). 25376608
TP53 loss ovarian cancer no benefit ReACp53 Preclinical Actionable In a preclincial study, ReACp53 did not induce cell death in ovarian cancer cells with loss of TP53 in culture (PMID: 26748848). 26748848
PTEN loss TP53 loss prostate cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, treatment with AZD5363 improved overall survival and progression-free survival in mouse models of prostate cancer with inactivated PTEN and TP53 (PMID: 26910118). 26910118
TP53 D259Y melanoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cells harboring TP53 D259Y in culture (PMID: 26343583). 26343583
TP53 D259Y melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 modestly inhibited soft agar growth of human melanoma cancer cells harboring TP53 D259Y in culture (PMID: 26343583). 26343583
TP53 D259Y melanoma sensitive Vemurafenib Preclinical Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of human melanoma cells TP53 D259Y in culture (PMID: 26343583). 26343583
TP53 R280K triple-receptor negative breast cancer sensitive YW3-56 Preclinical - Cell line xenograft Actionable In a preclinical study, YW3-56 inhibited proliferation of a human triple-negative breast cancer (TNBC) cell line harboring TP53 R280K in culture and inhibited tumor growth in TP53 R280K-mutant TNBC cell line xenograft models (PMID: 25612620). 25612620
TP53 R280K ovarian cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically in culture, resulting in reduced cell viability in patient derived ovarian cancer cells harboring TP53 R280K (PMID: 27179933). 27179933
TP53 R280K breast cancer sensitive Ganetespib Preclinical Actionable In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 R280K in culture (PMID: 26009011). 26009011
TP53 R248W VHL inact mut clear cell renal cell carcinoma resistant PT2399 Preclinical - Cell culture Actionable In a preclinical study, TP53 R248W was associated with resistance to PT2399 in VHL-defective clear cell renal cell carcinoma cell lines in culture (PMID: 27595393). 27595393
KRAS G12D PIK3CA H1047R TP53 R248W colorectal cancer no benefit Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment did not improve tumor growth stabilization compared to single agent in patient-derived xenograft models of colorectal cancer harboring KRAS G12D, PIK3CA H1047R and TP53 R248W (PMID: 26272063). 26272063
KRAS G12D PIK3CA H1047R TP53 R248W colorectal cancer predicted - sensitive BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 stabilized tumor growth of patient-derived xenograft models of colorectal cancer harboring KRAS G12D, PIK3CA H1047R, and TP53 R248W (PMID: 26272063). 26272063
KRAS G12D PIK3CA H1047R TP53 R248W colorectal cancer resistant Selumetinib Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft models of colorectal cancer harboring KRAS G12D, PIK3CA H1047R, and TP53 R248W did not respond to Selumetinib (AZD6244) treatment (PMID: 26272063). 26272063
KRAS G12C PIK3CA H1047R TP53 R248W colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12C, PIK3CA H1047R, and TP53 R248W (PMID: 26272063). 26272063
TP53 R248W non-small cell lung carcinoma sensitive APR-246 + Cisplatin Preclinical Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of non-small lung cancer cells harboring TP53 R248W in culture (PMID: 26086967). 26086967
RB1 K240Sfs*22 TP53 R248W Her2-receptor negative breast cancer predicted - resistant Fulvestrant + Palbociclib Clinical Study Actionable In a clinical case study, RB1 K240Sfs*22 and TP53 R248W were identified in the circulating tumor DNA of a patient with estrogen receptor positive, progesterone receptor positive, and Erbb2 (Her2)-negative, invasive ductal carcinoma at the time of disease progression after 5 months of Ibrance (palbociclib) and Faslodex (fulvestrant) combination treatment (PMID: 29236940). 29236940
TP53 P151H ovarian cancer sensitive APR-246 + Cisplatin Preclinical - Patient cell culture Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) resulted in strong synergism, thereby reducing cell viability in patient derived ovarian cancer cells harboring TP53 P151H in culture (PMID: 27179933). 27179933
ALK wild-type TP53 C176F neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783). 26438783
KRAS G12V PIK3CA Q546K TP53 R282W colorectal cancer sensitive Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment resulted in enhanced tumor growth stabilization compared to single agent in patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA Q546K and TP53 R282W (PMID: 26272063). 26272063
KRAS G12V PIK3CA Q546K TP53 R282W colorectal cancer predicted - sensitive Selumetinib Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) inhibited tumor growth of patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA Q546K, and TP53 R282W (PMID: 26272063). 26272063
KRAS G12V PIK3CA Q546K TP53 R282W colorectal cancer decreased response BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 delayed tumor growth of patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA Q546K, and TP53 R282W (PMID: 26272063). 26272063
BRAF V600E PIK3CA P449T TP53 R273H colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and growth of colorectal cancer cells harboring BRAF V600E, PIK3CA P449T, and TP53 R273H in culture and in cell line xenograft models, but did not have synergistic effect on apoptosis (PMID: 26272063). 26272063
TP53 R273H non-small cell lung carcinoma sensitive APR-246 + Cisplatin Preclinical Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of non-small lung cancer cells harboring TP53 R248W in culture (PMID: 26086967). 26086967
KRAS G12D TP53 S127Y lung adenocarcinoma sensitive Dasatinib + Demcizumab Preclinical - Pdx Actionable In a preclinical study, combination of Sprycel (dasatinib) and Demcizumab (OMP-21M18) treatment resulted in durable tumor inhibition in patient-derived animal models of lung adenocarcinoma harboring KRAS G12D and TP53 S127Y (PMID: 26855149). 26855149
TP53 R248Q ovarian cancer sensitive ReACp53 Preclinical - Pdx & cell culture Actionable In a preclinical study, ReACp53 rescued p53 activity and decreased viability of ovarian cancer cells harboring TP53 R248Q in culture, and induced tumor regression in patient-derived ovarian cancer xenograft models harboring TP53 R248Q (PMID: 26748848). 26748848
TP53 R248Q ovarian cancer sensitive APR-246 + Cisplatin Preclinical Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of a Platinol (cisplatin)-resistant ovarian cancer cell line harboring TP53 R248Q in culture and inhibited tumor growth in TP53 R248Q-carrying ovarian cancer cell line xenograft models (PMID: 26086967). 26086967
TP53 R248Q Advanced Solid Tumor sensitive Ganetespib Preclinical Actionable In a preclinical study, Ganetespib extended survival by 48% in mice with tumors expressing TP53 R248Q (PMID: 26009011). 26009011
TP53 R248Q acute myeloid leukemia resistant ALRN-6924 Preclinical - Cell culture Actionable In a preclinical study, ALRN-6924 did not inhibit the growth of acute myeloid leukemia cells harboring TP53 R248Q in culture (PMID: 29643228). 29643228
TP53 R249S hepatocellular carcinoma sensitive CP-31398 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 R249S in culture, and inhibited tumor growth in xenograft models (PMID: 26250460). 26250460
KRAS mut TP53 G105C TP53 V157fs ovarian cancer predicted - sensitive MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in partial response in an ovarian cancer patient harboring TP53 G105C, V157fs and mutations in Kras (PMID: 27998224). 27998224
ALK wild-type TP53 P177T neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783). 26438783
TP53 P177T osteosarcoma resistant Nutlin-3a Preclinical Actionable In a preclinical study, TP53 P177T resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). 21643018
PIK3CA H1047R TP53 S90fs ovarian clear cell adenocarcinoma decreased response DS-7423 Preclinical - Cell culture Actionable In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring PIK3CA H1047R and TP53 S90fs*33 demonstrated reduced sensitivity to DS-7423 in culture (PMID: 24504419). 24504419
TP53 inact mut ovarian cancer sensitive MK-1775 + Carboplatin + Paclitaxel Phase I Actionable In a Phase I trial, ovarian patients with TP53 deficiency had a 78.6% response rate to MK-1775 in combination with carboplatin and paclitaxel (J Clin Oncol 31, 2013 (suppl; abstr 5518)). detail...
TP53 inact mut breast carcinoma predicted - sensitive CHIR-124 + Irinotecan Preclinical - Cell line xenograft Actionable In a preclinical study, sequential treatment with Camptosaur (irinotecan) and CHIR-124 enhanced tumor growth inhibition compared to either agent alone in a breast carcinoma cell line xenograft model with defective TP53 (PMID: 17255282). 17255282
TP53 inact mut breast carcinoma predicted - sensitive CHIR-124 + SN-38 Preclinical - Cell culture Actionable In a preclinical study, SN-38 and CHIR-124 demonstrated synergy in a breast carcinoma cell line with defective TP53, resulting in increased cell cycle arrest and apoptosis in culture (PMID: 17255282). 17255282
TP53 inact mut chronic lymphocytic leukemia predicted - sensitive AZD6482 Preclinical Actionable In a preclinical study, AZD6482 induced cell death in TP53-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132). 26563132
TP53 inact mut ovarian carcinoma sensitive ReACp53 Preclinical Actionable In a preclinical study, ReACp53 induced cell death and decreased proliferation of ovarian carcinoma cells harboring TP53 mutations in culture, but did not effect viability of ovarian carcinoma cells with wild-type TP53 (PMID: 26748848). 26748848
TP53 inact mut ovarian cancer sensitive Nutlin-3 + Cisplatin Preclinical Actionable In a preclinical study, Nutlin-3 and cisplatin worked cooperatively to induce apoptosis in ovarian cancer cell lines with TP53 inactivating mutations in culture (PMID: 25964101). 25964101
TP53 inact mut lung small cell carcinoma sensitive APR-246 Preclinical - Cell line xenograft Actionable In a preclinical study, APR-246 induced apoptosis in small-cell lung cancer (SCLC) cell lines and decreased tumor growth in SCLC cell line xenograft models harboring Tp53 inactivating mutations (PMID: 21415220). 21415220
TP53 inact mut chronic lymphocytic leukemia sensitive AZD6738 + Ibrutinib Preclinical Actionable In a preclinical study, AZD6738 sensitized TP53-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132). 26563132
TP53 inact mut breast cancer sensitive AMG 900 Preclinical Actionable In a preclinical study, breast cancer cell lines with TP53 loss of function mutations had more pronounced apoptosis after treatment with AMG 900 in culture (PMID: 24091768). 24091768
TP53 inact mut breast cancer sensitive MK-1775 + Radiotherapy Preclinical Actionable In a preclinical study, MK-1775 increased the efficacy of radiation in breast cancer cells with defective TP53 in culture (PMID: 21799033). 21799033
TP53 inact mut ovarian cancer sensitive LB-100 + Cisplatin Preclinical Actionable In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in a cisplatin-resistant ovarian cancer cell line harboring a TP53 inactivating mutation in culture (PMID: 25376608). 25376608
KRAS G12D PTEN dec exp TP53 R306* colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12D, decreased PTEN expression, and TP53 R306* (PMID: 26272063). 26272063
KRAS G13D PIK3CA H1047R TP53 wild-type colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring KRAS G13D and PIK3CA H1047R in culture and in cell line xenograft models (PMID: 26272063). 26272063
KRAS mut + TP53 wild-type colorectal cancer sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 induced activation of Tp53 target genes and inhibited growth of a colorectal cancer (CRC) cell line with wild-type TP53, that also harbored a KRAS mutation, in culture and inhibited tumor growth in a TP53 wild-type KRAS-mutant CRC cell line xenograft model (PMID: 25567130). 25567130
KRAS mut + TP53 wild-type colorectal cancer sensitive AMG 232 + Irinotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of AMG 232 and Camptosaur (irinotecan) inhibited tumor growth in a TP53 wild-type colorectal cancer cell line xenograft model, which also harbors a KRAS mutation, with increased efficacy over either agent alone (PMID: 25567130). 25567130
KRAS mut + TP53 wild-type Advanced Solid Tumor sensitive Oxaliplatin + ABT-737 Preclinical Actionable In a preclinical study, Eloxatin (oxaliplatin), in combination with ABT-737, was only effective in tumor cell lines carrying KRAS mutants and wild-type TP53 (PMID: 21468686). 21468686
KRAS mut + TP53 wild-type colorectal cancer sensitive ABT-263 + Alpelisib + CGM097 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Mekinist (trametinib), and CGM097 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a KRAS mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
KRAS G12D PIK3CA H1047R TP53 wild-type colorectal cancer no benefit Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment did not improve tumor growth stabilization compared to single agent in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D and PIK3CA H1047R (PMID: 26272063). 26272063
KRAS G12D PIK3CA H1047R TP53 wild-type colorectal cancer decreased response Selumetinib Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) delayed tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D and PIK3CA H1047R (PMID: 26272063). 26272063
KRAS G12D PIK3CA H1047R TP53 wild-type colorectal cancer predicted - sensitive BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 inhibited tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D and PIK3CA H1047R (PMID: 26272063). 26272063
ALK F1174L TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). 26438783
KRAS G12V PIK3CA E545K TP53 wild-type colorectal cancer decreased response Selumetinib Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) delayed tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12V and PIK3CA E545K (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 wild-type colorectal cancer sensitive Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment resulted in enhanced tumor growth stabilization compared to single agent in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12V and PIK3CA E545K (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 wild-type colorectal cancer decreased response BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 delayed tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12V and PIK3CA E545K (PMID: 26272063). 26272063
BRAF V600E PIK3CA H1047R TP53 wild-type colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture (PMID: 26272063). 26272063
TP53 wild-type colorectal cancer sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment resulted in a partial response in a patient with colorectal cancer (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type osteosarcoma sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type osteosarcoma cells in culture (PMID: 26162687). 26162687
TP53 wild-type melanoma sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type melanoma cells in culture (PMID: 26162687). 26162687
TP53 wild-type melanoma sensitive APR-246 Preclinical - Cell line xenograft Actionable In a preclinical study, APR-246 inhibited growth of TP53 wild-type melanoma cells in 3D culture and in cell line xenograft models (PMID: 21239882). 21239882
TP53 wild-type breast cancer sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 enhanced radiation-induced cytotoxicity in TP53 wild-type breast cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type acute myeloid leukemia sensitive CTX-1 + Nutlin-3 Preclinical Actionable In a preclinical study, the combination of CTX-1 and Nutlin-3 resulting in improved survival time in mouse models of acute myeloid leukemia using TP53 wild-type primary human acute myeloid leukemia cells (PMID: 26883273). 26883273
TP53 wild-type endometrioid ovary carcinoma sensitive thioureidobutyronitrile Preclinical - Cell line xenograft Actionable In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment increased Tp53 and Cdkn1a protein levels, resulted in growth inhibition of TP53 wild-type endometrioid ovary carcinoma cells in culture and in cell line xenograft models (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). detail...
TP53 wild-type papillary thyroid carcinoma sensitive APG-115 Preclinical - Cell line xenograft Actionable In a preclinical study, a TP53 wild-type dedifferentiated papillary thyroid carcinoma cell line treated with APG-115 demonstrated decreased cell viability and induction of cell cycle arrest and apoptosis in culture, and tumor growth suppression and tumor regression in xenograft models (PMID: 28498808). 28498808
TP53 wild-type non-small cell lung carcinoma sensitive CEP-8983 + Cisplatin Preclinical Actionable In a preclinical study, the combination of CEP-8983 and Platinol (cisplatin) worked synergistically to induce cell death in non-small cell lung cancer cell lines in culture, irrespective of TP53 status (PMID: 23428903). 23428903
TP53 wild-type colorectal cancer predicted - sensitive MLN0128 + PD-0325901 Preclinical - Pdx & cell culture Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically induced apoptosis in TP53 wild-type but not TP53 mutated colorectal cancer cell lines in culture, and demonstrated anti-tumor activity in TP53 wild-type but not TP53 mutated patient-derived xenograft models (PMID: 26272063). 26272063
TP53 wild-type acute leukemia sensitive SAR405838 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR405838 inhibited growth of TP53 wild-type acute leukemia cells in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). 25145672
TP53 wild-type sarcoma sensitive MK-1775 + Gemcitabine Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination of MK-1775 and Gemzar (gemcitabine) induced cell death in a variety of sarcoma cell lines and inhibited tumor growth in a patient-derived sarcoma xenograft model, independent of TP53 mutational status (PMID: 23520471). 23520471
TP53 wild-type salivary gland adenoid cystic carcinoma predicted - sensitive SAR405838 Preclinical - Pdx Actionable In a preclinical study, treatment with SAR405838 (MI-773) resulted in activation of Mdm2 and Tp53 in patient-derived salivary gland adenoid cystic carcinoma (ACC) cells in culture, and led to induction of apoptosis and tumor regression in ACC patient-derived xenograft (PDX) models with wild-type TP53 (PMID: 26936915). 26936915
TP53 wild-type acute myeloid leukemia sensitive Cytarabine + RO6839921 Preclinical - Cell line xenograft Actionable In a preclinical study, RO6839921 and Cytosar-U (cytarabine) combination treatment demonstrated anti-tumor activity in TP53 wild-type disseminated acute myeloid leukemia cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). detail...
TP53 wild-type liposarcoma sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment resulted in a partial response in a patient with liposarcoma (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type non-small cell lung carcinoma sensitive AMG 232 + Carboplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of AMG 232 and Paraplatin (carboplatin) worked synergistically to inhibit tumor growth in a TP53 wild-type non-small cell lung cancer cell line xenograft model, with increased efficacy over either agent alone (PMID: 25567130). 25567130
TP53 wild-type non-small cell lung carcinoma sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 induced activation of Tp53 target genes and inhibited growth of a non-small cell lung cancer (NSCLC) cell line with wild-type TP53 in culture and inhibited tumor growth in a TP53 wild-type NSCLC cell line xenograft model (PMID: 25567130). 25567130
TP53 wild-type colon cancer sensitive MK-1775 + PF-00477736 Preclinical Actionable In a preclinical study, MK-1775, in combination with the Chk1 inhibitor, PF-00477736, showed efficacy in various human cancer cell lines (breast, ovarian, colon, prostate), independently of p53 status (PMID: 22713237). 22713237
TP53 wild-type acute myeloid leukemia sensitive RO6839921 Preclinical - Cell line xenograft Actionable In a preclinical study, RO6839921 demonstrated anti-tumor activity in TP53 wild-type disseminated acute myeloid leukemia cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). detail...
TP53 wild-type neuroblastoma predicted - sensitive GSK2830371 Preclinical Actionable In a preclinical study, GSK2830371 inhibited proliferation of neuroblastoma cell lines carrying wild-type TP53 in culture (PMID: 25658463). 25658463
TP53 wild-type Merkel cell carcinoma sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment in a patient with Merkel cell carcinoma resulted in a complete response (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type lung carcinoma sensitive AZD6738 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, AZD6738 treatment increased sensitivity to radiotherapy in a lung carcinoma cell line harboring wild-type TP53 in culture, resulting in a greater decrease in cell survival compared to radiation treatment alone (PMID: 28062704). 28062704
TP53 wild-type breast cancer predicted - sensitive SAR405838 Preclinical - Pdx Actionable In a preclinical study, SAR405838 (MI-77301) induced p53 signaling and inhibited tumor growth in patient-derived xenograft models of endocrine therapy-resistant breast cancer with wild-type TP53, and induced cell-cycle arrest and inhibited growth of patient-derived endocrine therapy-resistant breast cancer cells in culture (PMID: 27765850). 27765850
TP53 wild-type Advanced Solid Tumor sensitive CTX-1 + Nutlin-3 Preclinical Actionable In a preclinical study, CTX-1 and Nutlin-3 worked cooperatively to induce cell death in several TP53 wild-type human tumor cell lines in culture (PMID: 26883273). 26883273
TP53 wild-type melanoma sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 enhanced radiation-induced cytotoxicity in TP53 wild-type melanoma cells in culture and in cell line xenograft models (PMID: 26162687). 26162687
TP53 wild-type lung large cell carcinoma resistant NSC319726 Preclinical - Cell line xenograft Actionable In a preclinical study, NSC319726 did not inhibit tumor growth in xenograft models of TP53 wild-type lung large cell carcinoma (PMID: 22624712). 22624712
TP53 wild-type neuroblastoma predicted - sensitive Carboplatin + GSK2830371 Preclinical Actionable In a preclinical study, GSK283071 and Paraplatin (carboplatin) worked synergistically to inhibit proliferation of neuroblastoma cell lines carrying wild-type TP53 (PMID: 25658463). 25658463
TP53 wild-type Advanced Solid Tumor decreased response Pazopanib + Vorinostat Phase I Actionable In a Phase I study, patients with advanced solid tumor harboring TP53 mutations had increased progression-free survival and overall survival than TP53 wild-type patients after treatment with Votrient (pazopanib) in combination with Zolinza (vorinostat) (J Clin Oncol 32:5s, 2014 (suppl; abstr 2576)). detail...
TP53 wild-type osteosarcoma sensitive CPUY201112 Preclinical Actionable In a preclinical study, CPUY201112 reduced viability and induced apoptosis in an osteosarcoma cell line with wild-type TP53 in culture, and had a limited effect on an osteosarcoma cell line lacking TP53 (PMID: 26743233). 26743233
TP53 wild-type salivary gland adenoid cystic carcinoma predicted - sensitive Cisplatin + SAR405838 Preclinical - Pdx Actionable In a preclinical study, the combination of SAR405838 (MI-773) and Platinol (cisplatin) resulted in increased Tp53 and Mdm2 expression, and demonstrated improved efficacy over either agent alone in TP53 wild-type patient-derived xenograft (PDX) models of salivary gland adenoid cystic carcinoma, resulting in tumor regression without tumor rebound after cessation of therapy (PMID: 27550999). 27550999
TP53 wild-type medulloblastoma sensitive JQ1 Preclinical Actionable In a preclinical study, medulloblastoma cell lines with TP53 mutations had significantly less sensitivity to the BET inhibitor, JQ1, than cell lines carrying wild-type TP53 (PMID: 24231268). 24231268
TP53 wild-type neuroblastoma predicted - sensitive Doxorubicin + GSK2830371 Preclinical Actionable In a preclinical study, GSK283071 and Adriamycin (doxorubicin) worked synergistically to inhibit proliferation of neuroblastoma cell lines carrying wild-type TP53 (PMID: 25658463). 25658463
TP53 wild-type colon cancer sensitive CPUY201112 Preclinical Actionable In a preclinical study, CPUY201112 reduced viability and induced apoptosis in a colon cancer cell line with wild-type TP53 in culture, and had a limited effect on a colon cancer cell line lacking TP53 (PMID: 26743233). 26743233
TP53 wild-type Advanced Solid Tumor predicted - sensitive ALRN-6924 Phase I Actionable In a Phase I trial, treatment with ALRN-6924 in patients with advanced solid tumors and lymphomas resulted in a disease control rate of 45% (25/55), with 2 patients experiencing a complete response, 2 patients achieving a partial response, and 21 patients demonstrating stable disease (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type ovarian cancer predicted - sensitive Ad.p53-DC vaccine Phase I Actionable In Phase I and Phase II clinical trials, various forms of p53 gene therapy (such as adenoviral-p53) have been shown to be generally safe and have demonstrated clinical efficacy in patients with ovarian cancer (PMID: 12082455; PMID: 19621448; PMID: 21927947; PMID: 15297186; PMID: 12082456). 15297186 21927947 19621448 12082455 12082456
TP53 wild-type acute myeloid leukemia sensitive CTX-1 Preclinical Actionable In a preclinical study, CTX-1 improved survival time in mouse models of acute myeloid leukemia using TP53 wild-type primary human acute myeloid leukemia cells (PMID: 26883273). 26883273
TP53 wild-type Advanced Solid Tumor sensitive CTX-1 Preclinical Actionable In a preclinical study, CTX-1 induced cell death in several solid tumor cell lines with wild-type TP53 in culture (PMID: 26883273). 26883273
TP53 wild-type Advanced Solid Tumor sensitive HDM201 Preclinical - Cell line xenograft Actionable In a preclinical study, HDM201 treatment resulted in tumor regression in various cell line xenograft models of Tp53 wild-type tumors (Cancer Res 2016;76(14 Suppl):Abstract nr 4855). detail...
TP53 wild-type prostate cancer sensitive SAR405838 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR405838 inhibited growth of TP53 wild-type prostate cancer cells in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). 25145672
TP53 wild-type colon cancer sensitive Trifluridine Preclinical - Cell culture Actionable In a preclinical study, treatment with Trifluridine (FTD) resulted in Tp53-dependent cell-cycle arrest and decreased expression of CyclinB1 and Cdk1 in a Tp53-proficient colon cancer cancer cell line in culture (PMID: 25700705). 25700705
TP53 wild-type ovarian cancer no benefit p53-SLP vaccine Phase II Actionable In a Phase II trial, p53-SLP vaccine was demonstrated to be safe, well tolerated and to induce p53-specific T-cell responses in ovarian cancer patients; however clinical impact was lacking (PMID: 19621448, PMID: 21328579). 21328579 19621448
TP53 wild-type peripheral T-cell lymphoma sensitive ALRN-6924 Phase I Actionable In a Phase I trial, ALRN-6924 treatment in a patient with peripheral T-cell lymphoma resulted in a complete response (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type fibrosarcoma sensitive Doxil + RO6839921 Preclinical - Cell line xenograft Actionable In a preclinical study, RO6839921 and Doxil combination treatment demonstrated sustained survival benefit in TP53 wild-type fibrosarcoma cell line xenograft models (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A156). detail...
TP53 wild-type non-small cell lung carcinoma sensitive Seliciclib Preclinical - Cell culture Actionable In a preclinical study, Roscovotine (seliciclib) induced substantial apoptosis in non-small cell lung carcinoma cells overexpressing wild-type TP53 in culture (PMID: 22862161). 22862161
TP53 wild-type lymphoma predicted - sensitive ALRN-6924 Phase I Actionable In a Phase I trial, treatment with ALRN-6924 in patients with advanced solid tumors and lymphomas resulted in a disease control rate of 45% (25/55), with 2 patients experiencing a complete response, 2 patients achieving a partial response, and 21 patients demonstrating stable disease (J Clin Oncol 35, 2017 (suppl; abstr 2505)). detail...
TP53 wild-type colon cancer sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 enhanced radiation-induced cytotoxicity in TP53 wild-type colon cancer cells in culture and in cell line xenograft models (PMID: 26162687). 26162687
TP53 wild-type colon cancer sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type colon cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type breast cancer sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type breast cancer cells in culture (PMID: 26162687). 26162687
TP53 wild-type acute myeloid leukemia sensitive ALRN-6924 Preclinical - Patient cell culture Actionable In a preclinical study, ALRN-6924 inhibited growth of cells derived from patients with TP53 wild-type acute myeloid leukemia in culture, and inhibited leukemia cell growth, prolonged survival in cell line xenograft models (PMID: 29643228). 29643228
TP53 wild-type colorectal cancer sensitive Prodigiosin Preclinical Actionable In a preclinical study, Prodigiosin inhibited self-renewal of Tp53 wild-type colorectal cancer cell lines in culture (PMID: 26759239). 26759239
TP53 wild-type lung cancer sensitive AMG 232 Preclinical - Cell culture Actionable In a preclinical study, AMG 232 activated Tp53 signaling, resulted in growth inhibition of TP53 wild-type lung cancer cell lines in culture (PMID: 26162687). 26162687
TP53 wild-type colorectal cancer predicted - sensitive MK-8745 Preclinical - Cell culture Actionable In a preclinical study, MK-8745 treatment resulted in apoptosis in Tp53 wild-type colorectal cancer cells in culture (PMID: 22293494). 22293494
TP53 wild-type lung cancer sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 enhanced radiation-induced cytotoxicity in TP53 wild-type lung cancer cell lines in culture and in cell line xenograft models (PMID: 26162687). 26162687
TP53 wild-type liposarcoma predicted - sensitive MK-8242 Phase I Actionable In a Phase I trial, MK-8242 demonstrated safety and some preliminary clinical activity in patients with advanced solid tumors, particularly those with TP53 wild-type liposarcoma (LPS), with an overall response rate (ORR) of 6.4% (3/41; all partial responses), all in patients with LPS (ORR in LPS 11.1% (3/27)), and a median progression-free survival in LPS of 237 days (PMID: 28240971). 28240971
TP53 wild-type Advanced Solid Tumor sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 induced activation of Tp53 target genes and inhibited growth of several human tumor cell lines with wild-type TP53 in culture and in cell line xenograft models (PMID: 25567130). 25567130
TP53 wild-type colon cancer sensitive SAR405838 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR405838 inhibited growth of TP53 wild-type colon cancer cells in culture and resulted in tumor regression in cell line xenograft models (PMID: 25145672). 25145672
TP53 wild-type Advanced Solid Tumor unknown MK-8242 Phase I Actionable In a Phase I trial, MK-8242 demonstrated safety and some preliminary clinical activity in patients with TP53 wild-type advanced solid tumors, particularly those with liposarcoma (LPS), with an overall response rate (ORR) of 6.4% (3/41; all partial responses), all in patients with LPS (ORR in LPS 11.1% (3/27)), and 75.6% (31/41) of patients achieving stable disease (PMID: 28240971). 28240971
TP53 wild-type osteosarcoma sensitive AMG 232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 enhanced radiation-induced cytotoxicity in TP53 wild-type osteosarcoma cells in culture and in cell line xenograft models (PMID: 26162687). 26162687
TP53 wild-type non-small cell lung carcinoma sensitive AMG 232 + Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of AMG 232 and Platinol (cisplatin) worked synergistically to inhibit tumor growth in a TP53 wild-type non-small cell lung cancer cell line xenograft model, with increased efficacy over either agent alone, resulting in tumor stasis (PMID: 25567130). 25567130
TP53 wild-type colon carcinoma sensitive MPI-0479605 Preclinical Actionable In a preclinical study the TTK (MPS1) inhibitor, MPI-0479605, inhibited cell cycle progression of colon carcinoma cells deficient for Tp53 with equivalent efficacy to cells with wild-type Tp53 (PMID: 21980130). 21980130
EGFR exon 19 del TP53 wild-type non-small cell lung carcinoma sensitive unspecified EGFR tyrosine kinase inhibitor Clinical Study Actionable In a clinical study, non-small cell lung carcinoma patients harboring an EGFR exon 19 deletion and TP53 wild-type exon 8 demonstrated a median progression-free survival of 16.8 months following first-line treatment with an EGFR tyrosine kinase inhibitor, such as Iressa (gefitinib), Tarceva (erlotinib), Gilotrif (afatinib), or Dacomitinib, compared with 4.2 months in patients harboring a TP53 exon 8 mutation and EGFR exon 19 deletion (PMID: 27780855). detail... 27780855
BRAF V600E PTEN loss TP53 wild-type colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). 26272063
ALK wild-type TP53 wild-type neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). 26438783
TP53 wild-type RB1 wild-type mantle cell lymphoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). 17121911
TP53 wild-type RB1 wild-type lung carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of lung carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
TP53 wild-type RB1 wild-type colon carcinoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
TP53 wild-type RB1 wild-type breast carcinoma sensitive R547 Preclinical Actionable In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring wild-type Tp53 and Rb1 (PMID: 17121911). 17121911
TP53 wild-type RB1 wild-type melanoma sensitive R547 Preclinical - Cell line xenograft Actionable In a preclinical study, R547 inhibited proliferation of melanoma cell lines harboring wild-type Tp53 and Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). 17121911
KRAS G12D PIK3CA E545K PIK3CA H1047L TP53 wild-type colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment resulted in tumor growth stabilization in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D, PIK3CA E545K and H1047L (PMID: 26272063). 26272063
ALK amp Tp53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). 26438783
ALK mut TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). 26438783
ALK F1245C TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). 26438783
BRAF mut + TP53 wild-type colorectal cancer sensitive ABT-263 + CGM097 + Dabrafenib + PF-04217903 Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
BRAF mut + TP53 wild-type melanoma sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). 25567130
BRAF mut + TP53 wild-type melanoma sensitive CGM097 + LGX818 Preclinical Actionable In a preclinical study, the combination of CGM097 and Encorafenib (LGX818) synergized to inhibit cell growth of a human melanoma cell line harboring mutant BRAF and wild-type TP53 in culture, and promoted tumor regression in xenograft models (Cancer Res October 1, 2014 74; 5466). detail...
ALK act mut TP53 wild-type neuroblastoma predicted - sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). 26438783
TP53 L194F breast cancer sensitive Tanespimycin Preclinical - Cell line xenograft Actionable In a preclinical study, Tanespimycin (17-AAG) inhibited tumor growth in human breast cancer cell line xenograft models harboring TP53 L194F (PMID: 26009011). 26009011
TP53 L194F breast cancer sensitive Vorinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Zolinza (vorinostat) inhibited tumor growth in human breast cancer cell line xenograft models harboring TP53 L194F (PMID: 26009011). 26009011
TP53 L194F breast cancer sensitive Ganetespib Preclinical Actionable In a preclinical study, Ganetespib inhibited growth of human breast cancer cells harboring TP53 L194F in culture (PIMD: 26009011). 26009011
TP53 L194F breast cancer sensitive Tanespimycin + Vorinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Tanespimycin (17-AAG) and Zolinza (vorinostat) were synergistic towards tumor growth inhibition in human breast cancer cell line xenograft models harboring TP53 L194F (PMID: 26009011). 26009011
TP53 I232S osteosarcoma resistant Nutlin-3a Preclinical Actionable In a preclinical study, TP53 I232S resulted in secondary resistance in an osteosarcoma cell line acquired during Nutlin-3 treatment (PMID: 21643018). 21643018
MET del exon14 TP53 N30fs lung large cell carcinoma sensitive Capmatinib Clinical Study Actionable In a clinical case study, Capmatinib (INC280) treatment resulted in decreased tumor volume by 53% in a patient with large cell lung carcinoma harboring MET deletion exon 14 and TP53 N30fs*14 (PMID: 25971938). 25971938
TP53 positive Advanced Solid Tumor sensitive MVAp53 Phase I Actionable In a phase I study, Ankara (MVAp53) demonstrated safety and efficacy in patients with metastatic colon, gastric and pancreas cancer stained positive for p53 (J Clin Oncol 31, 2013 (suppl; abstr 3089)). detail...
TP53 positive breast cancer sensitive Serdemetan Phase I Actionable In a Phase I trial, Serdemetan (JNJ-26854165) treatment induced a 102% increase of Tp53 expression in tumor tissue, resulted in partial response in a patient with breast cancer (PMID: 21831953). 21831953
TP53 positive Advanced Solid Tumor sensitive Serdemetan Phase I Actionable In a Phase I trial, Serdemetan (JNJ-26854165) treatment increased Tp53 expression in tumor and surrogate tissue, resulted in partial response in 1.8% (1/57) and stable disease in 38.6% (22/57) of patients with advanced solid tumors (PMID: 21831953). 21831953
TP53 positive Advanced Solid Tumor predicted - sensitive p28 Phase I Actionable In a Phase I trial, treatment with p28 was well-tolerated and demonstrated preliminary efficacy in patients with Tp53-positive advanced solid tumors, with complete response in 6% (1/15), partial response in 20% (3/15), and stable disease in 46% (7/15) of patients (PMID: 23449360). 23449360
TP53 positive ovarian cancer predicted - sensitive NU6027 + Temozolomide Preclinical - Cell culture Actionable In a preclinical study, NU6027 enhanced the efficacy of Temodar (temozolomide) in ovarian cancer cells with mismatch repair activity and positive for TP53 in culture, demonstrating a 50% greater decrease in cell survival compared to Temodar (temozolomide) alone (PMID: 21730979). 21730979
TP53 Y163C lung small cell carcinoma sensitive APR-246 + Cisplatin Preclinical Actionable In a preclinical study, the combination of APR-246 and Platinol (cisplatin) worked synergistically to inhibit growth of small lung cancer cells harboring TP53 Y163C in culture (PMID: 26086967). 26086967
TP53 negative breast cancer sensitive Avastin + Doxorubicin + Docetaxel Phase I Actionable In a pilot trial, TP53-negative breast cancer patients demonstrated increased survival following treatment with Avastin (bevacizumab) in combination with chemotherapy agents, Adriamycin (doxorubicin) and Taxotere (docetaxel), compared to patients with TP53-positive tumors (PMID: 21399868). 21399868
TP53 negative non-small cell lung carcinoma decreased response Seliciclib Preclinical - Cell culture Actionable In a preclinical study, TP53-null non-small cell lung carcinoma cells demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
BRAF V600E TP53 Q192K colon cancer sensitive Vemurafenib + Panitumumab Clinical Study Actionable In a clinical study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 28514312). 28514312
KRAS Q61L PIK3CA E542K TP53 T118Qfs*5 colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, but did not induce apoptosis in colorectal cancer cells harboring KRAS Q61L, PIK3CA E542K, and TP53 T118Qfs*5 in culture (PMID: 26272063). 26272063
TP53 A159V non-small cell lung carcinoma decreased response Seliciclib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 A159V demonstrated reduced sensitivity to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). 22862161
TP53 P72R sarcoma sensitive Doxorubicin + Ifosfamide Phase I Actionable In a Phase I clinical trial, sarcoma patients harboring TP53 P72R mutations had longer progression-free survival after treatment with Cyfos (ifosfamide) and Adriamycin (doxorubicin) (PMID: 23165797). 23165797
TP53 P72R estrogen-receptor negative breast cancer sensitive Doxorubicin + Flourouracil + Cyclophosphamide Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R who were estrogen receptor negative had a more favorable response to Doxil (doxorubicin) in combination with Adrucil (fluorouracil) and Cytoxan (cyclophosphamide) (PMID: 16243804). 16243804
TP53 P72R breast cancer predicted - sensitive Doxil Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations were reported to have a better response to anthracycline-based neoadjuvant therapies (PMID: 16243804). 16243804
TP53 P72R non-small cell lung carcinoma sensitive Camptosar + Cisplatin Phase I Actionable In phase I clinical studies, NSCLC patients with TP53 P72R mutations had a longer progression-free survival than wild-type TP53 patients, after combined treatment with Camptosar (irinotecan) and Platinol (cisplatin) (PMID: 18618574). 18618574
TP53 P72R breast cancer sensitive epirubicin Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations, who were also hormone receptor negative, demonstrated a favorable response to Ellence (epirubicin) in combination with other chemotherapeutic agents (PMID: 22903472). 22903472
TP53 P72R breast cancer predicted - sensitive Daunorubicin Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations were reported to have a better response to anthracycline-based neoadjuvant therapies (PMID: 16243804). 16243804
TP53 P72R breast cancer predicted - sensitive Daunoxome Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations were reported to have a better response to anthracycline-based neoadjuvant therapies (PMID: 16243804). 16243804