Gene Detail

Gene Symbol FBXW7
Synonyms AGO | CDC4 | FBW6 | FBW7 | FBX30 | FBXO30 | FBXW6 | hAgo | hCdc4 | SEL-10 | SEL10
Gene Description FBXW7, F-box/WD repeat-containing protein 7, is part of the SCF E3 ubiquitin-protein ligase complex. FBXW7 participates in the degradation of a variety of oncoproteins and is deleted or mutated in many cancers (PMID: 22673505), including colorectal (PMID: 28424412).
Entrez Id 55294
Chromosome 4
Map Location 4q31.3
Canonical Transcript NM_033632

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
Q275* nonsense loss of function - predicted FBXW7 Q275* results in a premature truncation of the Fbxw7 protein at amino acid 275 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), FBXW7 Q275* is predicted to lead to a loss of Fbxw7 function.
R367* nonsense loss of function - predicted FBXW7 R367* results in a premature truncation of the Fbxw7 protein at amino acid 367 of 707 (UniProt.org). Due to the loss of the WD repeat domain, R367* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
W486* nonsense loss of function - predicted FBXW7 W486* results in a premature truncation of the Fbxw7 protein at amino acid 486 of 707 (Uniprot.org). W486* is predicted to confer a loss of function to the Fbxw7, as demonstrated by increased tumorigenesis in cultured cells (PMID: 24838835).
H379R missense unknown FBXW7 H379R lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). H379R has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
T15_G16insTP insertion unknown FBXW7 T15_G16insTP results in the insertion of two amino acids in the Fbxw7 protein between amino acids 15 and 16 (UniProt.org). T15_G16insTP has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
H460Y missense unknown FBXW7 H460Y lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). H460Y has been identified in sequencing studies (PMID: 29029407), but literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R505G missense unknown FBXW7 R505G lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505G has been identified in the scientific literature (PMID: 26155992, PMID: 27852700), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
inact mut unknown loss of function FBXW7 inact mut indicates that this variant results in a loss of function of the FBXW7 protein. However, the specific amino acid change has not been identified.
L301P missense unknown FBXW7 L301P lies within the F-box domain of the Fbxw7 protein (UniProt.org). L301P has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Aug 2018).
S398F missense unknown FBXW7 S398F lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). S398F has been identified in sequencing studies (PMID: 29996881), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S462Y missense no effect - predicted FBXW7 S462Y lies within the WD 3 repeat domain of the Fbxw7 protein (UniProt.org). S462Y is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599).
R465L missense loss of function FBXW7 R465L lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R465L confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in activation of a Notch-driven reporter (PMID: 19340001).
S476I missense unknown FBXW7 S476I lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). S476I has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R224* nonsense loss of function - predicted FBXW7 R224* results in a premature truncation of the Fbxw7 protein at amino acid 224 of 707 (UniProt.org). Due to the loss of all functional domains (UniProt.org), R224* is predicted to lead to a loss of Fbxw7 protein function.
K239Q missense unknown FBXW7 K239Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). K239Q has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R224Q missense unknown FBXW7 R224Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R224Q has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
K11R missense loss of function - predicted FBXW7 K11R does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). K11R is predicted to confer a loss of function to the Fbxw7 protein, as demonstrated by disruption of the NSL1 function of the Fbxw7 protein in cell culture (PMID: 20815813).
W446C missense unknown FBXW7 W446C lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). W446C has been identified in sequencing studies (PMID: 23103869), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
W526L missense unknown FBXW7 W526L lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). W526L has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S227A missense loss of function - predicted FBXW7 S227A lies within a phosphorylation site in the Fbxw7 protein (UniProt.org). S227A is predicted to confer a loss of function to the Fbxw7 protein, as demonstrated by the inability of S227A to induce apoptosis in cell culture (PMID: 21620836).
S516R missense unknown FBXW7 S516R lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). S516R has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
E117del deletion unknown FBXW7 E117del results in the deletion of an amino acid in the Fbxw7 protein at amino acid 117 (UniProt.org). E117del has been identified in sequencing studies (PMID: 24909261, PMID: 27284958), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R543fs frameshift unknown FBXW7 R543fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 543 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). R543fs has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
H470P missense unknown FBXW7 H470P lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). H470P has been identified in the scientific literature (PMID: 18485478), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R505S missense unknown FBXW7 R505S lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505S has been identified in sequencing studies (PMID: 27101000, PMID: 25670083), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R505H missense unknown FBXW7 R505H lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). R505H has been identified in sequencing studies (PMID: 25617745, PMID: 28671688), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
V418M missense unknown FBXW7 V418M lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). V418M has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G499Vfs*25 frameshift loss of function - predicted FBXW7 G499Vfs*25 indicates a shift in the reading frame starting at amino acid 499 and terminating 25 residues downstream causing a premature truncation of the 707 amino acid Fbxw7 protein (UniProt.org). Due to the loss of several WD domains (UniProt.org), G499Vfs*25 is predicted to lead to a loss of Fbxw7 protein function.
G597E missense unknown FBXW7 G597E lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). G597E has been identified in sequencing studies (PMID: 23415222), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R441W missense unknown FBXW7 R441W lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). R441W has been identified in sequencing studies (PMID: 28581676), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
E369* nonsense loss of function - predicted FBXW7 E369* results in a premature truncation of the Fbxw7 protein at amino acid 369 of 707 (UniProt.org). Due to the loss of all WD repeat domains (UniProt.org), R369* is predicted to result in a loss of function.
W237* nonsense loss of function - predicted FBXW7 W237* results in a premature truncation of the Fbxw7 protein at amino acid 237 of 707 (UniProt.org). Due to the loss of the WD repeat domain, W237* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
S396N missense unknown FBXW7 S396N lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). S396N has been identified in sequencing studies (PMID: 28292439), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S582L missense unknown FBXW7 S582L lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). S582L has been identified in sequencing studies (PMID: 25450649, PMID: 27852700, PMID: 28120820), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R479L missense loss of function FBXW7 R479L lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479L confers a loss of function to the Fbxw7 protein as demonstrated by increased ubiquitination and decreased stability of the Fbxw7 protein (PMID: 22608923).
A503T missense unknown FBXW7 A503T lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). A503T has been identified in sequencing studies (PMID: 25148578), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
H500D missense unknown FBXW7 H500D lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). H500D has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R278* nonsense loss of function - predicted FBXW7 R278* results in a premature truncation of the Fbxw7 protein at amino acid 278 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R278* is predicted to result in a loss of function.
G437R missense unknown FBXW7 G437R lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G437R has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
D520N missense unknown FBXW7 D520N lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). D520N has been identified in sequencing studies (PMID: 22810696, PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
C386W missense unknown FBXW7 C386W lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). C386W has been identified in sequencing studies (PMID: 17457043), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
P285H missense unknown FBXW7 P285H lies within the F-box domain of the Fbxw7 protein (UniProt.org). P285H has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R465C missense loss of function FBXW7 R465C lies within the WD 3 repeat region of the Fbxw7 protein (UniProt.org). R465C confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in sustained NICD and MYC expression (PMID: 17646409) and also has impaired degradation of Klf5 (PMID: 2896335).
D600H missense unknown FBXW7 D600H lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). D600H has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
K404E missense unknown FBXW7 K404E lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). K404E has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
V265I missense unknown FBXW7 V265I does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). V265I has been identified in sequencing studies (PMID: 21282377), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G437E missense unknown FBXW7 G437E lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G437E has been identified in the scientific literature (PMID: 27879972), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G397D missense unknown FBXW7 G397D lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). G397D has been identified in the scientific literature (PMID: 14999283), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R658* nonsense unknown FBXW7 R658* results in a premature truncation of the Fbxw7 protein at amino acid 658 of 707 (UniProt.org). R658* is associated with decreased Fbxw7 protein level in cell culture, but does not result in increased tumorigenesis compared to wild-type Fbxw7 in mouse models (PMID: 24838835), and therefore its effect on Fbxw7 protein function is unknown.
R479H missense loss of function FBXW7 R479H lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479H confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in activation of a Notch-driven reporter (PMID: 17575125).
V464E missense unknown FBXW7 V464E lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). V464E has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
H460R missense loss of function - predicted FBXW7 H460R lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). H460R is predicted to confer a loss of function to the Fbxw7 protein, as demonstrated by overexpression of the Fbxw7 ubiquitination target protein, Ccne1 (PMID: 14507635).
G579W missense unknown FBXW7 G579W lies between WD repeats 5 and 6 of the Fbxw7 protein (UniProt.org). G579W has been identified in the scientific literature studies (PMID: 24755471, PMID: 27399335), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S558F missense unknown FBXW7 S558F lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). S558F has been identified in sequencing studies (PMID: 28256603), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S562L missense unknown FBXW7 S562L lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). S562L has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R479Q missense loss of function FBXW7 R479Q lies within the WD 3 repeat region of the Fbxw7 protein (UniProt.org). R479Q confers a loss of FBXW7-substrate interation and impairs substrate degradation by FBXW7, resulting in sustained NICD and MYC expression (PMID: 17646409, PMID: 25450649).
K299fs frameshift loss of function - predicted FBXW7 K299fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 299 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the WD repeat domains (UniProt.org), K299fs is predicted to lead to a loss of Fbxw7 protein function.
R179H missense unknown FBXW7 R179H does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R179H has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R465H missense loss of function FBXW7 R465H (corresponds to R385H in isoform 2) lies within the WD repeat 3 of the Fbxw7 protein (UniProt.org). R465H confers a loss of FBXW7-substrate interaction and impairs substrate degradation by FBXW7, resulting in sustained NICD and MYC expression (PMID: 17646409) and also has impaired degradation of Klf5 (PMID: 2896335).
S516N missense unknown FBXW7 S516N lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). S516N hasbeen identified in sequencing studies (PMID: 29106415), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
H420Y missense loss of function - predicted FBXW7 H420Y lies within the WD repeat 2 of the Fbxw7 protein (UniProt.org). H420Y is predicted to result in a loss of function, affecting substrate targeting in the Fbxw7 protein (PMID: 18485478).
S546L missense unknown FBXW7 S546L lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). S546L has been identified in sequencing studies (PMID: 26000489), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
T144R missense unknown FBXW7 T144R does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). T144R has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
K444fs frameshift loss of function - predicted FBXW7 K444fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 444 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to a loss of a majority of the WD repeat domains (UniProt.org), K444fs is predicted to lead to a loss of Fbxw7 protein function.
Q631* nonsense unknown FBXW7 Q631* results in a premature truncation of the Fbxw7 protein at amino acid 631 of 707 (UniProt.org). Q631* has been identified in sequencing studies (PMID: 24390348), but has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
D480Y missense unknown FBXW7 D480Y lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). D480Y has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R689W missense unknown FBXW7 R689W does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R689W has been identified in sequencing studies (PMID: 19245433), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S476R missense unknown FBXW7 S476R lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). S476R has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R479* missense loss of function - predicted FBXW7 R479* results in a premature truncation of the Fbxw7 protein at amino acid 479 of 707 (UniProt.org). Due to the disruption of the WD repeat domain, R479* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
D135Y missense unknown FBXW7 D135Y does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). D135Y has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G423* nonsense loss of function - predicted FBXW7 G423* results in a premature truncation of the Fbxw7 protein at amino acid 423 of 707 within the WD repeat domain (UniProt.org). G423* has not been characterized, however due to the loss of the WD repeat domain (UniProt.org), G423* is predicted to lead to a loss of Fbxw7 function.
T165fs frameshift loss of function - predicted FBXW7 T165fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 165 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of multiple functional domains, T165fs is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
D440N missense unknown FBXW7 D440N lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). D440N has been identified in sequencing studies (PMID: 17909001), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
Q47* nonsense loss of function - predicted FBXW7 Q47* results in a premature truncation of the Fbxw7 protein at amino acid 47 of 707 (UniProt.org). Due to the loss of all known functional domains, Q47* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
H500R missense unknown FBXW7 H500R lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). H500R has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
I435fs frameshift loss of function - predicted FBXW7 I435fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 435 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). Due to a loss of a majority of the WD repeat domains (UniProt.org), I435fs is predicted to lead to a loss of Fbxw7 protein function.
R505L missense loss of function FBXW7 R505L lies within the WD repeat 4 of the Fbxw7 protein (UniProt.org). R505L confers a loss of function on Fbxw7, as demonstrated by activation of the NOTCH pathway in cultured cells (PMID: 17646409) and the inability to bind substrates (PMID: 28522751).
V464M missense unknown FBXW7 V464M lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). V464M has been identified in sequencing studies (PMID: 28424412), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
wild-type none no effect Wild-type FBXW7 indicates that no mutation has been detected within the FBXW7 gene.
loss unknown loss of function FBXW7 loss indicates loss of the Fbxw7 gene, mRNA or protein.
E248D missense unknown FBXW7 E248D does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). E248D has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
K167T missense unknown FBXW7 K167T does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). K167T has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S601F missense unknown FBXW7 S601F lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). S601F has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R689Q missense no effect - predicted FBXW7 R689Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R689Q is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599).
R473fs frameshift loss of function - predicted FBXW7 R473fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 473 of 707, likely resulting in a premature truncation of the functional protein (UniProt.org). Due to the loss of the majority of the WD repeat domains (UniProt.org), R473fs is predicted to lead to a loss of Fbxw7 protein function.
R465Y missense loss of function - predicted FBXW7 R465Y lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R465Y has not been characterized however other R465 hotspots inactivate Fbxw7 therefore, R465Y is predicted to lead to a loss of function (PMID: 17646409, PMID: 17909001, PMID: 19340001).
S282* nonsense loss of function - predicted FBXW7 S282* results in a premature truncation of the Fbxw7 protein at amino acid 282 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), S282* is predicted to result in a loss of function.
A481V missense unknown FBXW7 A481V lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). A481V has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G667fs frameshift unknown FBXW7 G667fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 667 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). G667fs has been identified in the scientific literature, but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
D560G missense unknown FBXW7 D560G lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). D560G has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
V504I missense unknown FBXW7 V504I lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). V504I has been identified in sequencing studies (PMID: 17909001), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
P247T missense unknown FBXW7 P247T does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). P247T has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G437V missense unknown FBXW7 G437V lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). G437V has been identified in sequencing studies (PMID: 23263491), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R465P missense loss of function - predicted FBXW7 R465P lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R465P has not been characterized, however other R465 hotspots inactivate Fbxw7, therefore, R465P is predicted to lead to a loss of function (PMID: 17646409, PMID: 17909001, PMID: 19340001).
R479G missense loss of function - predicted FBXW7 R479G lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479G has not been characterized, however other R479 hotspot mutations inactivate Fbxw7 therefore, R479G is predicted to lead to a loss of function (PMID: 17646409, PMID: 17575125, PMID: 22608923).
G423R missense unknown FBXW7 G423R lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G423R does not enhance xenograft tumor growth in animal models compared to controls (PMID: 24838835), however has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
L320I missense unknown FBXW7 L320I lies within the F-box domain of the Fbxw7 protein (UniProt.org). L320I has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
mutant unknown unknown FBXW7 mutant indicates and unspecified mutation in the FBXW7 gene.
G422C missense unknown FBXW7 G422C lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). G422C has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
del unknown loss of function FBXW7 del indicates a deletion of the FBXW7 gene.
R505C missense loss of function FBXW7 R505C lies within the WD 4 repeat region of the Fbxw7 protein (UniProt.org). R505C confers a loss of FBXW7-substrate interation and impairs substrate degradation by FBXW7, resulting in sustained NICD and MYC expression (PMID: 17646409) and also has impaired degradation of Klf5 (PMID: 2896335).
W526R missense unknown FBXW7 W526R lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). W526R has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
E192A missense unknown FBXW7 E192A does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). E192A has been identified in sequencing studies (PMID: 24586741, PMID: 26328274), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S426L missense unknown FBXW7 S426L lies within WD repeat 2 of the Fbxw7 protein (UniProt.org). S426L has not been characterized and therefore, its effect on Fbxw7 protein is unknown (PubMed, Nov 2018).
E287V missense unknown FBXW7 E287V lies within the F-box domain of the Fbxw7 protein (UniProt.org). E287V has been identified in sequencing studies (PMID: 22810696, PMID: 28924241), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G670fs frameshift unknown FBXW7 G670fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 670 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). G670fs has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
D600Y missense unknown FBXW7 D600Y lies within WD repeat 6 of the Fbxw7 protein (UniProt.org). D600Y has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R479S missense unknown FBXW7 R479S lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). R479S has been identified in sequencing studies (PMID: 23165447), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
P298L missense unknown FBXW7 P298L lies within the F-box domain of the Fbxw7 protein (UniProt.org). P298L has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
S668fs frameshift unknown FBXW7 S668fs results in a change in the amino acid sequence of the Fbxw7 protein beginning at aa 668 of 707, likely resulting in premature truncation of the functional protein (UniProt.org). S668fs has been identified in sequencing studies (PMID: 26373574). but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
D550Mfs*6 frameshift unknown FBXW7 D550Mfs*6 indicates a shift in the reading frame starting at amino acid 550 and terminating 6 residues downstream causing a premature truncation of the 707 amino acid Fbxw7 protein (UniProt.org). D550Mfs*6 has not been characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, May 2018).
V154I missense unknown FBXW7 V154I does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). V154I has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R658Q missense no effect - predicted FBXW7 R658Q lies within the WD 7 repeat domain of the Fbxw7 protein (UniProt.org). R658Q is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599).
T15_G16insP insertion loss of function FBXW7 T15_G16insP results in the insertion of a proline (P) in the Fbxw7 protein between amino acids 15 and 16 (UniProt.org). T15_G16insP results in decreased binding of Fbxw7 to cyclinE1 and aberrant Fbxw7 localization in cell culture (PMID: 17909001).
H500Y missense unknown FBXW7 H500Y lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). H500Y has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
H382N missense unknown FBXW7 H382N lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). H382N has been identified in sequencing studies (PMID: 26010451), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
W244* nonsense loss of function - predicted FBXW7 W244* results in a premature truncation of the Fbxw7 protein at amino acid 244 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), W244* is predicted to result in a loss of function.
R393* nonsense loss of function - predicted FBXW7 R393* results in a premature truncation of the Fbxw7 protein at amino acid 393 of 707 (UniProt.org). Due to the disruption of the WD repeat domain, R393* is predicted to lead to a loss of Fbxw7 protein function (UniProt.org).
R14Q missense unknown FBXW7 R14Q does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R14Q has been identified in sequencing studies (PMID: 22810696, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
I347M missense no effect - predicted FBXW7 I347M does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). I347M is predicted to have activity similar to wild-type Fbxw7 based on comparison and correlation analysis of induced gene expression signatures (PMID: 27147599).
I563T missense unknown FBXW7 I563T lies within WD repeat 5 of the Fbxw7 protein (UniProt.org). I563T has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G477S missense unknown FBXW7 G477S lies within WD repeat 3 of the Fbxw7 protein (UniProt.org). G477S has been identified in the scientific literature (PMID: 19109228), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G517E missense unknown FBXW7 G517E lies within WD repeat 4 of the Fbxw7 protein (UniProt.org). G517E has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R479P missense loss of function - predicted FBXW7 R479P lies within the WD repeat domain of the Fbxw7 protein (UniProt.org). R479P has not been characterized, however other R479 hotspot mutations inactivate Fbxw7 therefore, R479P is predicted to lead to a loss of function (PMID: 17646409, PMID: 17575125, PMID: 22608923).
R222* nonsense loss of function - predicted FBXW7 R222* results in a premature truncation of the Fbxw2 protein at amino acid 222 of 707 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R222* is predicted to result in a loss of function.
E113D missense unknown FBXW7 E113D does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). E113D has been identified in sequencing studies (PMID: 26182302), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
R179C missense unknown FBXW7 R179C does not lie within any known functional domains of the Fbxw7 protein (UniProt.org). R179C has been identified in sequencing studies (PMID: 27714650), but has not been biochemically characterized and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
G411S missense unknown FBXW7 G411S lies within WD repeat 1 of the Fbxw7 protein (UniProt.org). G411S has not been characterized in the scientific literature and therefore, its effect on Fbxw7 protein function is unknown (PubMed, Nov 2018).
Molecular Profile Protein Effect Treatment Approaches
FBXW7 Q275* loss of function - predicted mTORC1 Inhibitor
FBXW7 R367* loss of function - predicted mTORC1 Inhibitor
FBXW7 W486* loss of function - predicted mTORC1 Inhibitor
FBXW7 H379R unknown
FBXW7 T15_G16insTP unknown
FBXW7 H460Y unknown
FBXW7 R505G unknown
FBXW7 inact mut loss of function mTORC1 Inhibitor
FBXW7 L301P unknown
FBXW7 S398F unknown
FBXW7 S462Y no effect - predicted
FBXW7 R465L loss of function mTORC1 Inhibitor
FBXW7 S476I unknown
FBXW7 R224* loss of function - predicted mTORC1 Inhibitor
FBXW7 K239Q unknown
FBXW7 R224Q unknown
FBXW7 K11R loss of function - predicted mTORC1 Inhibitor
FBXW7 W446C unknown
FBXW7 W526L unknown
FBXW7 S227A loss of function - predicted mTORC1 Inhibitor
FBXW7 S516R unknown
FBXW7 E117del unknown
FBXW7 R543fs unknown
FBXW7 H470P unknown
FBXW7 R505S unknown
FBXW7 R505H unknown
FBXW7 V418M unknown
FBXW7 G499Vfs*25 loss of function - predicted mTORC1 Inhibitor
FBXW7 G597E unknown
FBXW7 R441W unknown
FBXW7 E369* loss of function - predicted mTORC1 Inhibitor
FBXW7 W237* loss of function - predicted mTORC1 Inhibitor
FBXW7 S396N unknown
FBXW7 S582L unknown
FBXW7 R479L loss of function mTORC1 Inhibitor
FBXW7 A503T unknown
FBXW7 H500D unknown
FBXW7 R278* loss of function - predicted mTORC1 Inhibitor
FBXW7 G437R unknown
FBXW7 D520N unknown
FBXW7 C386W unknown
FBXW7 P285H unknown
FBXW7 R465C loss of function mTORC1 Inhibitor
FBXW7 D600H unknown
FBXW7 K404E unknown
FBXW7 V265I unknown
FBXW7 G437E unknown
FBXW7 G397D unknown
FBXW7 R658* unknown
FBXW7 R479H loss of function mTORC1 Inhibitor
FBXW7 V464E unknown
FBXW7 H460R loss of function - predicted mTORC1 Inhibitor
FBXW7 G579W unknown
FBXW7 S558F unknown
FBXW7 S562L unknown
FBXW7 R479Q loss of function mTORC1 Inhibitor
FBXW7 K299fs loss of function - predicted mTORC1 Inhibitor
FBXW7 R179H unknown
FBXW7 R465H loss of function mTORC1 Inhibitor
FBXW7 S516N unknown
FBXW7 H420Y loss of function - predicted mTORC1 Inhibitor
FBXW7 S546L unknown
FBXW7 T144R unknown
FBXW7 K444fs loss of function - predicted mTORC1 Inhibitor
FBXW7 Q631* unknown
FBXW7 D480Y unknown
FBXW7 R689W unknown
FBXW7 S476R unknown
FBXW7 R479* loss of function - predicted mTORC1 Inhibitor
FBXW7 D135Y unknown
FBXW7 G423* loss of function - predicted mTORC1 Inhibitor
FBXW7 T165fs loss of function - predicted mTORC1 Inhibitor
FBXW7 D440N unknown
FBXW7 Q47* loss of function - predicted mTORC1 Inhibitor
FBXW7 H500R unknown
FBXW7 I435fs loss of function - predicted mTORC1 Inhibitor
FBXW7 R505L loss of function mTORC1 Inhibitor
FBXW7 V464M unknown
FBXW7 wild-type no effect
FBXW7 loss loss of function mTORC1 Inhibitor
FBXW7 E248D unknown
FBXW7 K167T unknown
FBXW7 S601F unknown
FBXW7 R689Q no effect - predicted
FBXW7 R473fs loss of function - predicted mTORC1 Inhibitor
FBXW7 R465Y loss of function - predicted mTORC1 Inhibitor
FBXW7 S282* loss of function - predicted mTORC1 Inhibitor
FBXW7 A481V unknown
FBXW7 G667fs unknown
FBXW7 D560G unknown
FBXW7 V504I unknown
FBXW7 P247T unknown
FBXW7 G437V unknown
FBXW7 R465P loss of function - predicted mTORC1 Inhibitor
FBXW7 R479G loss of function - predicted mTORC1 Inhibitor
FBXW7 G423R unknown
FBXW7 L320I unknown
FBXW7 mutant unknown
FBXW7 G422C unknown
FBXW7 del loss of function mTORC1 Inhibitor
FBXW7 R505C loss of function mTORC1 Inhibitor
FBXW7 W526R unknown
FBXW7 E192A unknown
FBXW7 S426L unknown
FBXW7 E287V unknown
FBXW7 G670fs unknown
FBXW7 D600Y unknown
FBXW7 R479S unknown
FBXW7 P298L unknown
FBXW7 S668fs unknown
FBXW7 D550Mfs*6 unknown
FBXW7 V154I unknown
FBXW7 R658Q no effect - predicted
FBXW7 T15_G16insP loss of function mTORC1 Inhibitor
FBXW7 H500Y unknown
FBXW7 H382N unknown
FBXW7 W244* loss of function - predicted mTORC1 Inhibitor
FBXW7 R393* loss of function - predicted mTORC1 Inhibitor
FBXW7 R14Q unknown
FBXW7 I347M no effect - predicted
FBXW7 I563T unknown
FBXW7 G477S unknown
FBXW7 G517E unknown
FBXW7 R479P loss of function - predicted mTORC1 Inhibitor
FBXW7 R222* loss of function - predicted mTORC1 Inhibitor
FBXW7 E113D unknown
FBXW7 R179C unknown
FBXW7 G411S unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FBXW7 inact mut breast cancer sensitive Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cells harboring a FBXW7 mutation demonstrated sensitivity to Rapamune (sirolimus) in culture and in cell line xenograft models (PMID: 18787170). 18787170
FBXW7 inact mut fibrolamellar carcinoma sensitive Sirolimus Phase I Actionable In a Phase I study, Rapamune (sirolimus) resulted in prolonged stable disease in a patient with hepatocellular fibrolamellar carcinoma harboring a FBXW7 mutation (PMID: 24586741). 24586741
FBXW7 inact mut Advanced Solid Tumor sensitive AR-42 Preclinical Actionable In a preclinical study, AR-42 inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor sensitive Entinostat Preclinical Actionable In a preclinical study, entinostat (MS-275) inhibited cancer cells from advanced solid tumors and hematological cells harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive AR-42 Preclinical Actionable In a preclinical study, AR-42 inhibited human hematologic cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive Belinostat Preclinical Actionable In a preclinical study, Beleodaq (belinostat) inhibited human hematologic cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive Entinostat Preclinical Actionable In a preclinical study, entinostat (MS-275) inhibited cancer cells from advanced solid tumors and hematological cells harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor resistant Docetaxel Preclinical Actionable In a preclinical study, human cancer cell lines harboring FBXW7 inactivating mutations were resistant to docetaxel in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor sensitive Belinostat Preclinical Actionable In a preclinical study, Beleodaq (belinostat) inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 R465C T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R465C conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
FBXW7 R479Q T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R479Q conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
FBXW7 R465H T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R465H conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
FBXW7 R465H lung adenocarcinoma sensitive Temsirolimus Clinical Study Actionable In a clinical case report, a patient with lung adenocarcinoma harboring FBXW7 R465H demonstrated tumor shrinkage when treated with Torisel (temsirolimus) (PMID: 24360397). 24360397
FBXW7 R505L T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R505L may conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
FBXW7 loss colon cancer sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) inhibited epithelial-mesenchymal transition, motility, and invasiveness in colon cancer cells lacking FBXW7 in culture (PMID: 23558291) 23558291
FBXW7 mutant Her2-receptor negative breast cancer predicted - sensitive LY3039478 Phase I Actionable In a Phase I trial, LY3039478 treatment resulted in partial response lasted 9.5 months in a patient with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring FBXW7 mutation (PMID: 30060061; NCT01695005). 30060061
FBXW7 del T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, homozygous deletion of FBXW7 is conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
FBXW7 R505C colorectal cancer resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cell lines with FBXW7 R505C demonstrated acquired resistance in regorafenib (PMID: 27399335). 27399335
FBXW7 R505C head and neck squamous cell carcinoma sensitive Vorinostat Preclinical Actionable In a preclinical study, Zolinza (vorinostat) inhibited growth of a head and neck squamous cell carcinoma cell line harboring FBXW7 R505C in culture (PMID: 23274910). 23274910
FBXW7 R505C T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R505C conferred resistance to gamma secretase inhibitor, MRK-300, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409