Gene Detail

Gene Symbol CDKN2A
Synonyms ARF | CDK4I | CDKN2 | CMM2 | INK4 | INK4A | MLM | MTS-1 | MTS1 | P14 | P14ARF | P16 | P16-INK4A | P16INK4 | P16INK4A | P19 | P19ARF | TP16
Gene Description CDKN2A, cyclin-dependent kinase inhibitor 2A, encodes p16 and p14ARF from alternate reading frames, which function to inhibit Cdk4 and Cdk6 and regulate Tp53 activity to promote cell-cycle arrest (PMID: 23875803, PMID: 17055429, PMID: 27428416). CDKN2A germline mutations are associated with familial atypical multiple mole melanoma and somatic mutations are highest in pancreatic, HNSCC, NSCLC, and melanoma (PMID: 27283171).
Entrez Id 1029
Chromosome 9
Map Location 9p21.3
Canonical Transcript NM_000077

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
R128W missense loss of function - predicted CDKN2A R128W lies within ANK repeat 4 of the Cdkn2a protein (UniProt.org). R128W is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a loss of Sp1 binding (PMID: 24163379).
E88* nonsense loss of function - predicted CDKN2A E88* results in a premature truncation of the Cdkn2a protein at amino acid 88 of 156 (UniProt.org). E88* has not been characterized, however, nonsense mutations downstream of E88 are inactivating (PMID: 9053859, PMID: 8668202), thus E88* is predicted to lead to a loss of Cdkn2a protein function.
M52R missense unknown CDKN2A M52R lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). M52R has not been characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
A102V missense unknown CDKN2A A102V lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). A102V has been identified in the scientific literature (PMID: 9053859), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
D108Y missense loss of function - predicted CDKN2A D108Y lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). D108Y is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of cell cycle control (PMID: 12606942).
N71S missense loss of function CDKN2A N71S lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). N71S confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, reduced binding to Cdk4 and Cdk6, and a reduced ability to cause cell cycle arrest in cell culture (PMID: 10491434, PMID: 20340136).
P81fs frameshift loss of function - predicted CDKN2A P81fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 81 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). P81fs has not been characterized, however, nonsense mutations downstream of P81 are inactivating (PMID: 9053859, PMID: 8668202), thus, P81fs is predicted to lead to a loss of Cdkn2a protein function.
L31V missense unknown CDKN2A L31V lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). L31V has not been characterized in the scientific literature and therefore, its effect on Cdk2na protein function is unknown (PubMed, Nov 2018).
Q50fs frameshift loss of function - predicted CDKN2A Q50fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 50 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). Q50fs has not been characterized, however, other nonsense mutations downstream of Q50 are inactivating (PMID: 9053859, PMID: 8668202), thus Q50fs is predicted to lead to a loss of Cdkn2a protein function.
A21P missense unknown CDKN2A A21P lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). A21P has been identified in the scientific literature (PMID: 27415609, PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
L78fs frameshift loss of function - predicted CDKN2A L78fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 78 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). L78fs has not been characterized, however, nonsense mutations downstream of L78 are inactivating (PMID: 9053859, PMID: 8668202), thus L78fs is predicted to lead to a loss of Cdkn2a protein function.
amp none no effect CDKN2A amplification indicates an increased number of copies of the CDKN2A gene. However, the mechanism causing the increase is unspecified.
D14G missense unknown CDKN2A D14G lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). D14G has been identified in sequencing studies (PMID: 26873401), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
A36P missense loss of function - predicted CDKN2A A36P lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). A36P is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by the inability to suppress reactive oxygen species formation (PMID: 23190892).
Q50H missense unknown CDKN2A Q50H lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). Q50H has been identified in sequencing studies (PMID: 30325992), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
M52fs frameshift loss of function - predicted CDKN2A M52fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 52 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). M52fs has not been characterized, however, nonsense mutations downstream of M52 are inactivating (PMID: 9053859, PMID: 8668202), thus, M52fs is predicted to lead to a loss of Cdkn2a protein function.
R112G missense loss of function CDKN2A R112G lies within ANK repeat 4 of the Cdkn2a protein (UniProt.org). R112G confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
W15* nonsense loss of function - predicted CDKN2A W15* results in a premature truncation of the Cdkn2a protein at amino acid 15 of 156 (UniProt.org). W15* has not been characterized, however, nonsense mutations downstream of W15 are inactivating (PMID: 9053859, PMID: 8668202), thus W15* is predicted to lead to a loss of Cdkn2a protein function.
L16P missense loss of function CDKN2A L16P lies within ANK repeat 1 domain of the Cdkn2a protein (UniProt.org). L16P confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
H83D missense unknown CDKN2A H83D lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). H83D has been identified in the scientific literature (PMID: 12614625), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Jun 2018).
positive unknown unknown CDKN2A positive indicates the presence of the CDKN2A gene, mRNA, and/or protein.
H123Q missense no effect - predicted CDKN2A H123Q lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). H123Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Cdkn2a (PMID: 29533785) and therefore, is predicted to have no effect on Cdkn2a protein function.
wild-type none no effect Wild-type CDKN2A indicates that no mutation has been detected within the CDKN2A gene.
A60V missense loss of function CDKN2A A60V lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). A60V confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062).
D84H missense loss of function CDKN2A D84H lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). D84H confers a loss of function to the Cdk2na protein as demonstrated by an inability to bind to Cdk4 and Cdk6 (PMID: 10498896).
P48R missense unknown CDKN2A P48R lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). P48R has been identified in sequencing studies (PMID: 25855536, PMID: 26336083), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
P70T missense unknown CDKN2A P70T lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). P70T has not been characterized in the scientific literature and therefore, its effect on Cdk2na protein function is unknown (PubMed, Nov 2018).
P114H missense unknown CDKN2A P114H lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). P114H has been identified in the scientific literature (PMID: 15195137, PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
A76fs frameshift loss of function - predicted CDKN2A A76fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 76 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). A76fs has not been characterized, however, nonsense mutations downstream of A76 are inactivating (PMID: 9053859, PMID: 8668202), thus A76fs is predicted to lead to a loss of Cdkn2a protein function.
A76T missense unknown CDKN2A A76T does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). A76T has been identified in sequencing studies (PMID: 26164066), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
S12* nonsense loss of function - predicted CDKN2A S12* results in a premature truncation of the Cdkn2a protein at amino acid 12 of 156 (UniProt.org). S12* has not been characterized, however, nonsense mutations downstream of S12 are inactivating (PMID: 9053859, PMID: 8668202), thus S12* is predicted to lead to a loss of Cdkn2a protein function.
E119* nonsense loss of function - predicted CDKN2A E119* results in a premature truncation of the Cdkn2a protein at amino acid 119 or 156 (UniProt.org). E119* has not been characterized, however, a nonsense mutation downstream of E119 is inactivating (PMID: 8668202), thus E119* is predicted to lead to a loss of Cdkn2a protein function.
D84V missense loss of function CDKN2A D84V lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). D84V confers a loss of function to the Cdk2na protein as demonstrated by an inability to bind to Cdk4 and Cdk6 (PMID: 10498896, PMID: 10491434).
G23A missense no effect - predicted CDKN2A G23A lies within the ANK repeat 1 of the Cdk2na protein (UniProt.org). G23A results in growth inhibition similar to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to have no effect on Cdkn2a protein function.
del deletion loss of function CDKN2A del indicates a deletion of the CDKN2A gene.
D84G missense loss of function CDKN2A D84G lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). D84G confers a loss of function to the Cdkn2a protein as demonstrated by a loss of Cdk binding, defective kinase inhibition, and aberrant proliferation of cells in culture (PMID: 10491434).
W110* nonsense loss of function CDKN2A W110* results in a premature truncation of the Cdkn2a protein at amino acid 110 of 156 (UniProt.org). W110* confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk binding and cell cycle control in culture (PMID: 9053859, PMID: 8668202).
A100S missense no effect - predicted CDKN2A A100S lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). A100S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Cdkn2a (PMID: 29533785) and therefore, is predicted to have no effect on Cdkn2a protein function.
I49S missense loss of function CDKN2A I49S lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). I49S confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
D108G missense unknown CDKN2A D108G does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). D108G has been identified in the scientific literature (PMID: 23770606), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
P81S missense unknown CDKN2A P81S lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). P81S has been identified in sequencing studies (PMID: 29489023, PMID: 27844328, PMID: 23851445), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
E33fs frameshift loss of function - predicted CDKN2A E33fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 33 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). E33fs has not been characterized, however, nonsense mutations downstream of E33 are inactivating (PMID: 9053859, PMID: 8668202), thus E33fs is predicted to lead to a loss of Cdkn2a protein function.
A60R missense loss of function CDKN2A A60R lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). A60R confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk4 and Cdk6 binding, and aberrant proliferation of cells in culture (PMID: 19260062, PMID: 20340136).
A102fs frameshift loss of function - predicted CDKN2A A102fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 102 of 156, likely resulting in premature truncation of the functional protein (UniProt). A102fs has not been characterized, however, nonsense mutations downstream of A102 are inactivating (PMID: 9053859, PMID: 8668202), thus A102fs is predicted to lead to a loss of Cdkn2a protein function.
A148T missense no effect CDKN2A A148T does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). A148T was shown to display similar activity to wild-type Cdkn2a including inhibition of cell growth in culture and binding to Cdk4 and Cdk6 (PMID: 10389768).
A73D missense unknown CDKN2A A73D does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). A73D has been identified in sequencing studies (PMID: 16354195), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R80Q missense unknown CDKN2A R80Q lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). R80Q has been identified in sequencing studies (PMID: 27311873), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
H98P missense loss of function CDKN2A H98P lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). H98P results in decreased inhibition of cell-cycle arrest and cyclin-D1/Cdk4 kinase activity by Cdkn2a in cell culture (PMID: 7777061).
P81T missense loss of function - predicted CDKN2A P81T lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). P81T is predicted to result in a loss of Cdkn2a protein function as demonstrated by its reduced ability to suppress ROS activity and regulate the cell cycle in vitro (PMID: 23190892).
R124C missense unknown CDKN2A R124C lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). R124C has been identified in sequencing studies (PMID: 25303977, PMID: 25780468), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
A20E missense unknown CDKN2A A20E lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). A20E has been identified in sequencing studies (PMID: 8589032), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
D84Y missense loss of function CDKN2A D84Y lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). D84Y confers a loss of function to the Cdk2na protein as demonstrated by an inability to bind to Cdk4 and Cdk6 (PMID: 10498896).
R99P missense loss of function - predicted CDKN2A R99P lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). R99P is predicted to confer a loss of function to the Cdkn2a protein, a demonstrated by loss of Cdkn2a cell-cycle regulatory activity, but does not affect the oxidative activity of Cdkn2a in cultured cells (PMID: 23190892).
D84N missense loss of function CDKN2A D84N lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). D84N confers a loss of function to the Cdk2na protein as demonstrated by an inability to bind to Cdk4 and Cdk6 (PMID: 10498896).
P48L missense loss of function - predicted CDKN2A P48L lies within the ANK2 domain of the Cdkn2a protein (UniProt.org). P48L is predicted to confer a loss of function to the Cdk2na protein, as demonstrated by loss of cell cycle control (PMID: 10491434).
N71K missense loss of function CDKN2A N71K lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). N71K confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
A68fs frameshift loss of function - predicted CDKN2A A68fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 68 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). A68fs has not been characterized, however, nonsense mutations downstream of A68 are inactivating (PMID: 9053859, PMID: 8668202), thus A68fs is predicted to lead to a loss of Cdkn2a protein function.
V82E missense unknown CDKN2A V82E lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). V82E has been identified in the scientific literature (PMID: 27245685), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Jun 2018).
D108N missense unknown CDKN2A D108N does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). The functional effect of D108N is conflicting, as it results in the destabilization of Cdkn2a compared to wild-type, but also demonstrates displacement of Cdc37 from CDK4 and CDK6 complexes similar to wild-type Cdkn2a (PMID: 29091774), and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
H83Q missense unknown CDKN2A H83Q lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). H83Q has been identified in sequencing studies (PMID: 12117769), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Jun 2018).
D14N missense unknown CDKN2A D14N lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). D14N has not been characterized in the scientific literature and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R124H missense no effect CDKN2A R124H lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). R124H has been reported to have activity similar to wild-type Cdkn2a in in vitro and cell culture assays (PMID: 10491434).
G35V missense loss of function CDKN2A G35V lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). G35V confers a loss of function to the Cdkn2a protein as demonstrated by a loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062).
L32P missense loss of function CDKN2A L32P lies within ANK repeat 1 of the Cdkn2a protein (UniProt.org). L32P confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
G23R missense loss of function - predicted CDKN2A G23R lies within the ANK repeat 1 of the Cdk2na protein (UniProt.org). G23R results in a loss of growth inhibition compared to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to result in a loss of Cdkn2a protein function.
M52I missense unknown CDKN2A M52I lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). M52I has been identified in sequencing studies (PMID: 19593635), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
Y44* nonsense loss of function - predicted CDKN2A Y44* results in a premature truncation of the Cdkn2a protein at amino acid 44 of 156 (UniProt.org). Y44* has not been characterized, however, nonsense mutations downstream of Y44 are inactivating (PMID: 9053859, PMID: 8668202), thus Y44* is predicted to lead to a loss of Cdkn2a protein function.
M52L missense unknown CDKN2A M52L lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). M52L has been identified in sequencing studies (PMID: 18948947, PMID: 29970484), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
V82fs frameshift loss of function - predicted CDKN2A V82fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 82 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). V82fs has not been characterized, however, nonsense mutations downstream of V82 are inactivating (PMID: 9053859, PMID: 8668202), thus V82fs is predicted to lead to a loss of Cdkn2a protein function.
D125fs frameshift unknown CDKN2A D125fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 125 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). D125fs has been identified in sequencing studies (PMID: 23525077, PMID: 8637233), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
S56fs frameshift loss of function - predicted CDKN2A S56fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 56 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). S56fs has not been characterized, however, nonsense mutations downstream of S56 are inactivating (PMID: 9053859, PMID: 8668202), thus S56fs is predicted to lead to a loss of Cdkn2a protein function.
A57V missense unknown CDKN2A A57V lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). The functional effect of A57V is conflicting, as it results in a partial loss of Cdk4 binding, but had no effect on cell proliferation (PMID: 19260062), and resulted in dysregulated levels of ROS and cell cycle distribution compared to wild-type Cdkn2a (PMID: 23190892), and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
G35R missense no effect - predicted CDKN2A G35R lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). G35R results in growth inhibition similar to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to have no effect on Cdkn2a protein function.
H83N missense loss of function - predicted CDKN2A H83N lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). H83N is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a reduction in the ability to inhibit Cdk4 kinase activity in an in-vitro assay (PMID: 9660926).
P81L missense loss of function CDKN2A P81L lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). P81L confers a loss of function to the Cdkn2a protein as demonstrated by a reduction in Cdk4 and Cdk6 binding as well as loss of cell cycle control (PMID: 10389768).
A127fs frameshift unknown CDKN2A A127fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 127 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). A127fs has been identified in sequencing studies (PMID: 9808520), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R58* nonsense loss of function - predicted CDKN2A R58* results in a premature truncation of the Cdkn2a protein at amino acid 58 or 156 (UniProt.org). R58* is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of Cdk binding (PMID: 8668202).
Q50R missense unknown CDKN2A Q50R lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). Q50R has been identified in the scientific literature (PMID: 29464027, PMID: 11477665), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R80* nonsense loss of function - predicted CDKN2A R80* results in a premature truncation of the Cdkn2a protein at amino acid 80 of 156. R80* is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of Cdk binding (PMID: 8668202).
V82M missense unknown CDKN2A V82M lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). V82M has been identified in sequencing studies (PMID: 29348365, PMID: 27311873), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R24P missense loss of function CDKN2A R24P lies within ANK repeat 1 of the Cdkn2a protein (UniProt.org). R24P confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
G23fs frameshift loss of function - predicted CDKN2A G23fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 23 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). G23fs has not been characterized, however, nonsense mutations downstream of G23 are inactivating (PMID: 9053859, PMID: 8668202), thus G23fs is predicted to lead to a loss of Cdkn2a protein function.
P114T missense unknown CDKN2A P114T lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). P114T has not been characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
M53I missense loss of function CDKN2A M53I lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). M53I confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization and loss of binding to Cdk4 in cell culture (PMID: 19260062, PMID: 20340136).
D74N missense loss of function - predicted CDKN2A D74N lies between the ANK2 and ANK3 domain of the Cdkn2a protein (UniProt.org). D74N is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a reduction in Cdk kinase inhibition (PMID: 10491434).
W110fs frameshift loss of function - predicted CDKN2A W110fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 110 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). W110fs has not been characterized, however, nonsense mutations downstream of W110 are inactivating (PMID: 8668202), thus W110fs is predicted to lead to a loss of Cdkn2a protein function.
A68T missense no effect - predicted CDKN2A A68T lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). A68T results in decreased binding of Cdkn2a to Cdk4 and altered subcellular localization of Cdkn2a, but induces cell-cycle arrest similar to wild-type Cdkn2a in culture (PMID: 11518711, PMID: 18990760) and in one of two cell lines, induced similar cell proliferation and cell viability as wild-type Cdkn2a (PMID: 29533785) and therefore, is predicted to have no effect on Cdkn2a protein function.
V126D missense loss of function - predicted CDKN2A V126D lies within the ANK4 domain of the Cdkn2a protein (UniProt.org). V126D is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by reduced Cdk binding (PMID: 8668202).
L31R missense loss of function CDKN2A L31R lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). L31R confers a loss of function to the Cdkn2a protein as demonstrated by the inability to inhibit kinase activity of the Cdk7 complex in culture (PMID: 11003668).
inact mut unknown loss of function CDNK2A inact mut indicates that this variant results in a loss of function of the Cdnk2a protein. However, the specific amino acid change has not been identified.
H83Y missense loss of function - predicted CDKN2A H83Y lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). H83Y is predicted to confer a loss of function to the Cdk2na protein, as demonstrated by loss of cell cycle control (PMID: 10491434).
Y44fs frameshift loss of function - predicted CDKN2A Y44fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 44 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). Y44fs has not been characterized, however, nonsense mutations downstream of Y44 are inactivating (PMID: 9053859, PMID: 8668202), thus Y44fs is predicted to lead to a loss of Cdkn2a protein function.
P114S missense loss of function CDKN2A P114S lies within ANK repeat 4 of the Cdkn2a protein (UniProt.org). P114S confers a loss of function to the Cdkn2a protein as demonstrated by a loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062).
G35W missense loss of function - predicted CDKN2A G35W lies within the ANK repeat 1 of the Cdk2na protein (UniProt.org). G35W results in a loss of growth inhibition compared to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to result in a loss of Cdkn2a protein function.
E120D missense unknown CDKN2A E120D lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). E120D has not been characterized in the scientific literature and therefore, its effect on Cdkn2a protein is unknown (PubMed, Nov 2018).
E88K missense loss of function CDKN2A E88K lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). E88K confers a loss of function to the Cdkn2a protein as demonstrated by loss of inhibitory binding to Cdk4 and Cdk6 (PMID: 10498896).
F90fs frameshift loss of function - predicted CDKN2A F90fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 90 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). P90fs has not been characterized, however, nonsense mutations downstream of F90 are inactivating (PMID: 9053859, PMID: 8668202), thus F90fs is predicted to lead to a loss of Cdkn2a protein function.
R87L missense loss of function CDKN2A R87L lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). R87L confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk6 kinase inhibition and a reduction in the ability to induce cell cycle arrest in culture (PMID: 10491434).
A36G missense unknown CDKN2A A36G lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). A36G has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
L65P missense unknown CDKN2A L65P lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). L65P results in intermediate cell proliferation compared to wild-type Cdkn2a in culture (PMID: 24659262), but also demonstrates reduced binding to CDK4 (PMID: 15235029), and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R58fs frameshift loss of function - predicted CDKN2A R58fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 58 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). R58fs has not been characterized, however, nonsense mutations downstream of R58 are inactivating (PMID: 9053859, PMID: 8668202), thus R58fs is predicted to lead to a loss of Cdkn2a protein function.
L16fs frameshift loss of function - predicted CDKN2A L16fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 16 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). L16fs has not been characterized, however, nonsense mutations downstream of L16 are inactivating (PMID: 9053859, PMID: 8668202), thus, L16fs is predicted to lead to a loss of Cdkn2a protein function.
G23S missense unknown CDKN2A G23S lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). G23S results in intermediate loss of growth inhibition compared to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
L94P missense loss of function - predicted CDKN2A L94P lies within the ANK repeat 3 of the Cdk2na protein (UniProt.org). L94P results in a loss of growth inhibition compared to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to result in a loss of Cdkn2a protein function.
S56N missense unknown CDKN2A S56N lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). S56N has been identified in the scientific literature (PMID: 29807574, PMID: 9414654), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
G23C missense loss of function - predicted CDKN2A G23C lies within the ANK repeat 1 of the Cdk2na protein (UniProt.org). G23C results in a loss of growth inhibition compared to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to result in a loss of Cdkn2a protein function.
D84A missense unknown CDKN2A D84A lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). D84A has been identified in sequencing studies (PMID: 21325014) but has not been biochemically characterized and therefore, its effect on Cdkn2a protein is unknown (PubMed, Sep 2018).
L97R missense loss of function CDKN2A L97R lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). L97R confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 19260062, PMID: 20340136).
V51I missense unknown CDKN2A V51I lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). V51I has been identified in sequencing studies (PMID: 8640773), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Dec 2017).
D108V missense unknown CDKN2A D108V does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). D108V has been identified in sequencing studies (PMID: 26919633, PMID: 29301828), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
W15fs frameshift loss of function - predicted CDKN2A W15fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 15 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). W15fs has not been characterized, however, nonsense mutations downstream of W15 are inactivating (PMID: 9053859, PMID: 8668202), thus W15fs is predicted to lead to a loss of Cdkn2a protein function.
D74Y missense loss of function - predicted CDKN2A D74Y does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). D74Y is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of Cdk4 binding in culture (PMID: 19260062).
Q50P missense loss of function - predicted CDKN2A Q50P lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). Q50P is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a loss of binding to Cdk4 in a yeast assay (PMID: 14508519).
C72fs frameshift loss of function - predicted CDKN2A C72fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 72 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). C72fs has not been characterized, however, nonsense mutations downstream of C72 are inactivating (PMID: 9053859, PMID: 8668202), thus C72fs is predicted to lead to a loss of Cdkn2a protein function.
R87W missense loss of function CDKN2A R87W lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). R87W confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062).
R80L missense loss of function - predicted CDKN2A R80L lies within ANK repeat 3 the Cdkn2a protein (UniProt.org). R80L is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a reduction in the ability to induce cell cycle arrest (PMID: 10491434).
D108H missense loss of function - predicted CDKN2A D108H lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). D108H is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of cell cycle control (PMID: 12606942).
E69* nonsense loss of function - predicted CDKN2A E69* results in a premature truncation of the Cdkn2a protein at amino acid 69 of 156 (UniProt.org). E69* is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of Cdk binding (PMID: 8668202).
S56I missense loss of function CDKN2A S56I lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). S56I confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization and reduced binding to Cdk4 in cell culture (PMID: 20340136).
N42H missense unknown CDKN2A N42H does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). N42H has been identified in sequencing studies (PMID: 24436120), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
G111D missense unknown CDKN2A G111D lies within ANK repeat 4 of the Cdkn2a protein (UniProt.org). G111D has been identified in sequencing studies (PMID: 8747595, PMID: 22991414), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
G45S missense unknown CDKN2A G45S lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). G45S has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
R128fs frameshift unknown CDKN2A R128fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 128 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). R128fs has been identified in the scientific literature (PMID: 12853981), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
G23V missense loss of function - predicted CDKN2A G23V lies within the ANK repeat 1 of the Cdk2na protein (UniProt.org). G23V results in a loss of growth inhibition compared to wild-type Cdkn2a protein in culture (PMID: 24659262), and therefore, is predicted to result in a loss of Cdkn2a protein function.
E119K missense unknown CDKN2A E119K lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). E119K has not been characterized in the scientific literature and therefore, its effect on Cdkn2a protein is unknown (PubMed, Nov 2018).
E120* nonsense loss of function - predicted CDKN2A E120* results in a premature truncation of the Cdkn2a protein at amino acid 120 of 156. E120* is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a loss of Cdk binding (PMID: 8668202).
negative unknown loss of function CDKN2A negative indicates a lack of the CDKN2A gene, mRNA, and/or protein.
Q50* nonsense loss of function - predicted CDKN2A Q50* results in a premature truncation of the Cdkn2a protein at amino acid 50 of 156 (UniProt.org). Q50* is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by loss of Cdk binding (PMID: 8668202).
G35E missense no effect - predicted CDKN2A G35E lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). G35E results in growth inhibition similar to wild-type Cdkn2a in culture (PMID: 24659262), and therefore, is predicted to have no effect on Cdkn2a protein function.
T77P missense loss of function CDKN2A T77P lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). T77P confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062).
R112P missense unknown CDKN2A R112P lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). R112P has been identified in sequencing studies (PMID: 8895759), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Feb 2018).
loss none loss of function CDKN2A loss indicates loss of the CDKN2A gene, mRNA or protein.
T77fs frameshift loss of function - predicted CDKN2A T77fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 77 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). T77fs has not been characterized, however, nonsense mutations downstream of T77 are inactivating (PMID: 9053859, PMID: 8668202), thus T77fs is predicted to lead to a loss of Cdkn2a protein function.
N42fs frameshift loss of function - predicted CDKN2A N42fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 42 of 156, likely resulting in premature truncation of the functional protein (UniProt). N42fs has not been characterized, however, nonsense mutations downstream of N42 are inactivating (PMID: 9053859, PMID: 8668202), thus N42fs is predicted to lead to a loss of Cdkn2a protein function.
E69G missense loss of function CDKN2A E69G lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). E69G confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk4 and Cdk6 binding, and aberrant proliferation of cells in culture (PMID: 19260062, PMID: 20340136).
R87P missense loss of function CDKN2A R87P lies within the ANK3 domain of the Cdkn2a protein (UniProt.org). R87P confers a loss of function to the Cdkn2a protein as demonstrated by a reduction in Cdk4 and Cdk6 binding as well as loss of cell cycle control (PMID: 10491434).
A20P missense loss of function - predicted CDKN2A A20P lies within the ANK repeat 1 of the Cdkn2a protein (UniProt.org). A20P is predicted to confer a loss of function to the Cdkn2a protein, as demonstrated by a reduction in Cdk4 inhibitory activity (PMID: 19110720).
H83R missense unknown CDKN2A H83R lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). H83R has been identified in sequencing studies (PMID: 22817889), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Jun 2018).
N71I missense loss of function CDKN2A N71I lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). N71I confers a loss of function to the Cdkn2a protein as demonstrated by mislocalization, loss of binding to Cdk4 and Cdk6, and elevated Ki67 indicative of increased proliferation in cell culture (PMID: 20340136).
P114L missense loss of function CDKN2A P114L lies within the ANK4 domain of the Cdkn2a protein (UniProt.org). P114L confers a loss of function to the Cdkn2a protein as demonstrated by inability to suppress Rb phosphorylation and loss of cell cycle control (PMID: 9053859).
A60fs frameshift loss of function - predicted CDKN2A A60fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at aa 60 of 156, likely resulting in premature truncation of the functional protein (UniProt.org). A60fs has not been characterized, however, nonsense mutations downstream of A60 are inactivating (PMID: 9053859, PMID: 8668202), thus A60fs is predicted to lead to a loss of Cdkn2a protein function.
G67S missense unknown CDKN2A G67S lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). The functional effect of G67S is conflicting, as G67S has been reported to reduce binding to Cdk proteins, but is still capable of inducing G1 arrest in cultured cells (PMID: 11518711, PMID: 20340136).
C72* nonsense loss of function - predicted CDKN2A C72* results in a premature truncation of the Cdkn2a protein at amino acid 72 of 156 (UniProt.org). C72* has not been characterized, however, nonsense mutations downstream of C72 are inactivating (PMID: 9053859), thus C72* is predicted to lead to a loss of Cdkn2a protein function.
G35A missense loss of function CDKN2A G35A lies within ANK repeat 1 of the Cdkn2a protein (UniProt.org). G35A confers a loss of function to the Cdkn2a protein, as demonstrated by a partial loss of Cdk4 binding and aberrant proliferation of cells in culture (PMID: 19260062).
C72S missense unknown CDKN2A C72S lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). C72S has not been characterized in the scientific literature and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
mutant unknown unknown CDKN2A mutant indicates an unspecified mutation in the CDKN2A gene.
S43I missense unknown CDKN2A S43I does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). S43I has been identified in sequencing studies (PMID: 14556920), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
Y129* nonsense unknown CDKN2A Y129* results in a premature truncation of the Cdkn2a protein at amino acid 129 of 156 (UniProt.org). Y129* has been identified in sequencing studies (PMID: 30291346, PMID: 23565280, PMID: 25855536), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
D74V missense unknown CDKN2A D74V does not lie within any known functional domains of the Cdkn2a protein (UniProt.org). D74V has been identified in sequencing studies (PMID: 29625247, PMID: 16354195), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
L130R missense unknown CDKN2A L130R lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). L130R has been identified in sequencing studies (PMID: 25303977), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Jun 2018).
R131C missense unknown CDKN2A R131C lies within the ANK repeat 4 of the Cdkn2a protein (UniProt.org). R131C has been identified in sequencing studies (PMID: 12870051), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
A57T missense unknown CDKN2A A57T lies within the ANK repeat 2 of the Cdkn2a protein (UniProt.org). A57T has been identified in sequencing studies (PMID: 27077911, PMID: 25530832), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
G101W missense loss of function CDKN2A G101W lies within ANK repeat 3 of the Cdkn2a protein (UniProt.org). G101W confers a loss of function to the Cdkn2a protein as demonstrated by loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062, PMID: 20340136).
R80P missense unknown CDKN2A R80P lies within the ANK repeat 3 of the Cdkn2a protein (UniProt.org). R80P has been identified in sequencing studies (PMID: 26919633), but has not been biochemically characterized and therefore, its effect on Cdkn2a protein function is unknown (PubMed, Nov 2018).
T79fs frameshift loss of function - predicted CDKN2A T79fs results in a change in the amino acid sequence of the Cdkn2a protein beginning at 79 of 156, likely resulting in a premature truncation of the functional protein (UniProt.org). T79fs has not been characterized, however, nonsense mutations downstream of T79 are inactivating (PMID: 9053859, PMID: 8668202), thus T79fs is predicted to lead to a loss of Cdkn2a protein function.
G23D missense loss of function CDKN2A G23D lies within the first ANK repeat of the Cdkn2a protein (UniProt.org). G23D results in a loss of Cdkn2a protein function, evidenced by loss of CDK4 binding, reduced inhibition of pRb phosphorylation, and impaired cell cycle arrest in cultured cells (PMID: 19712690, PMID: 19260062).
G67R missense loss of function CDKN2A G67R lies within ANK repeat 2 of the Cdkn2a protein (UniProt.org). G67R confers a loss of function to the Cdkn2a protein as demonstrated by a loss of Cdk4 binding, and aberrant proliferation of cells in culture (PMID: 19260062).
over exp none no effect CDKN2A over exp indicates an over expression of the Cdkn2a protein. However, the mechanism causing the over expression is unspecified.
Molecular Profile Protein Effect Treatment Approaches
CDKN2A R128W loss of function - predicted
CDKN2A E88* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A M52R unknown
CDKN2A A102V unknown
CDKN2A D108Y loss of function - predicted
CDKN2A N71S loss of function
CDKN2A P81fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A L31V unknown
CDKN2A Q50fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A21P unknown
CDKN2A L78fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A amp no effect
CDKN2A D14G unknown
CDKN2A A36P loss of function - predicted
CDKN2A Q50H unknown
CDKN2A M52fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A R112G loss of function
CDKN2A W15* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A L16P loss of function
CDKN2A H83D unknown
CDKN2A positive unknown
CDKN2A pos RB1 inact mut
CDKN2A H123Q no effect - predicted
CDKN2A wild-type no effect
CDKN2A A60V loss of function
CDKN2A D84H loss of function
CDKN2A P48R unknown
CDKN2A P70T unknown
CDKN2A P114H unknown
CDKN2A A76fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A76T unknown
CDKN2A S12* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A E119* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A D84V loss of function
CDKN2A G23A no effect - predicted
EML4-ALK CDKN2A del FGFR1 T141R SMAD4 Q83*
CDKN2A del loss of function CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A D84G loss of function
CDKN2A W110* loss of function CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A100S no effect - predicted
CDKN2A I49S loss of function
CDKN2A D108G unknown
CDKN2A P81S unknown
CDKN2A E33fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A60R loss of function
CDKN2A A102fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A148T no effect
CDKN2A A73D unknown
CDKN2A R80Q unknown
CDKN2A H98P loss of function
CDKN2A P81T loss of function - predicted
CDKN2A R124C unknown
CDKN2A A20E unknown
CDKN2A D84Y loss of function
CDKN2A R99P loss of function - predicted
CDKN2A D84N loss of function
CDKN2A P48L loss of function - predicted
CDKN2A N71K loss of function
CDKN2A A68fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A V82E unknown
CDKN2A D108N unknown
CDKN2A H83Q unknown
CDKN2A D14N unknown
CDKN2A R124H no effect
CDKN2A G35V loss of function
CDKN2A L32P loss of function
CDKN2A G23R loss of function - predicted
CDKN2A M52I unknown
CDKN2A Y44* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A M52L unknown
CDKN2A V82fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A D125fs unknown
CDKN2A S56fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A57V unknown
CDKN2A G35R no effect - predicted
CDKN2A H83N loss of function - predicted
CDKN2A P81L loss of function
CDKN2A A127fs unknown
CDKN2A R58* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A Q50R unknown
CDKN2A R80* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A V82M unknown
CDKN2A R24P loss of function
CDKN2A G23fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A P114T unknown
CDKN2A M53I loss of function
CDKN2A D74N loss of function - predicted
CDKN2A W110fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A A68T no effect - predicted
CDKN2A V126D loss of function - predicted
CDKN2A L31R loss of function
CDKN2A inact mut loss of function
CDKN2A H83Y loss of function - predicted
CDKN2A Y44fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A P114S loss of function
CDKN2A G35W loss of function - predicted
CDKN2A E120D unknown
CDKN2A E88K loss of function
CDKN2A F90fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A R87L loss of function
CDKN2A A36G unknown
CDKN2A L65P unknown
CDKN2A R58fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A L16fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A G23S unknown
CDKN2A L94P loss of function - predicted
CDKN2A S56N unknown
CDKN2A G23C loss of function - predicted
CDKN2A D84A unknown
CDKN2A L97R loss of function
CDKN2A V51I unknown
CDKN2A D108V unknown
CDKN2A W15fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A D74Y loss of function - predicted
CDKN2A Q50P loss of function - predicted
CDKN2A C72fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A R87W loss of function
CDKN2A R80L loss of function - predicted
CDKN2A D108H loss of function - predicted
CDKN2A E69* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A S56I loss of function
CDKN2A N42H unknown
CDKN2A G111D unknown
CDKN2A G45S unknown
CDKN2A R128fs unknown
CDKN2A G23V loss of function - predicted
CDKN2A E119K unknown
CDKN2A E120* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A negative loss of function
CDKN2A Q50* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A G35E no effect - predicted
CDKN2A T77P loss of function
CDKN2A R112P unknown
CDKN2A loss loss of function CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
NRAS Q61K CDKN2A loss
CDKN2A loss KRAS wild-type
CDKN2A loss NRAS mutant
CDKN2A T77fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A N42fs loss of function - predicted
CDKN2A E69G loss of function
CDKN2A R87P loss of function
CDKN2A A20P loss of function - predicted
CDKN2A H83R unknown
CDKN2A N71I loss of function
CDKN2A P114L loss of function
CDKN2A A60fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A G67S unknown
CDKN2A C72* loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A G35A loss of function
CDKN2A C72S unknown
CDKN2A mutant unknown
BRAF V600E CDKN2A mut
BRAF mut KRAS mut CDKN2A mut
NRAS mut CDKN2A mut
PIK3CA mutant CDKN2A mutant
CDKN2A mut MET del exon14 PDGFRA mut SMAD4 Q249H
CDKN2A S43I unknown
CDKN2A Y129* unknown
CDKN2A D74V unknown
CDKN2A L130R unknown
CDKN2A R131C unknown
CDKN2A A57T unknown
CDKN2A G101W loss of function
CDKN2A R80P unknown
CDKN2A T79fs loss of function - predicted CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor
CDKN2A G23D loss of function
CDKN2A G67R loss of function
CDKN2A over exp no effect
CDKN2A over exp SMARCB1 negative
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CDKN2A pos RB1 inact mut glioblastoma multiforme resistant Palbociclib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived glioblastoma cells harboring RB1 truncation mutation and expressing Cdkn2a were resistant to Ibrance (palbociclib) in culture (PMID: 22711607). 22711607
EML4-ALK CDKN2A del FGFR1 T141R SMAD4 Q83* pancreatic ductal adenocarcinoma predicted - sensitive Alectinib Clinical Study Actionable In a clinical case study, a pancreatic ductal adenocarcinoma patient harboring EML4-ALK along with CDKN2A deletion, FGFR1 T141R, SMAD4 Q83*, and a TP53 splice site mutation, experienced disease progression after 2 months of Xalkori (crizotinib) treatment, then received Alecensa (alectinib) and remained on treatment for at least 3 months (PMID: 28476735). 28476735
EML4-ALK CDKN2A del FGFR1 T141R SMAD4 Q83* pancreatic ductal adenocarcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a pancreatic ductal adenocarcinoma patient harboring EML4-ALK along with CDKN2A deletion, FGFR1 T141R, SMAD4 Q83*, and a TP53 splice site mutation, experienced disease progression after 2 months of Xalkori (crizotinib) treatment, then received Alecensa (alectinib) and remained on treatment for at least 3 months (PMID: 28476735). 28476735
CDKN2A del glioblastoma multiforme sensitive Palbociclib Preclinical - Pdx & cell culture Actionable In a preclinical study, Ibrance (palbociclib) inhibited proliferation of patient-derived glioblastoma cells harboring homozygous deletion of CDKN2A in culture and prolonged survival in patient-derived xenograft models (PMID: 22711607). 22711607
CDKN2A del lung cancer predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of CDKN2A-deleted lung cancer (PMID: 26140595). 26140595
CDKN2A R80* stomach carcinoma sensitive Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, a gastric carcinoma cell line harboring CDKN2A R80* was sensitive to Ibrance (palbociclib) both in culture and in cell line xenograft models (PMID: 26380006, PMID: 20952405). 26380006 20952405
CDKN2A loss pancreatic cancer decreased response HMN-214 + PD0332991 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the activity of HMN-214 in pancreatic cancer cell lines with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss non-small cell lung carcinoma sensitive Palbociclib Phase II Actionable In a Phase II trial, treatment with Ibrance (palbociclib) resulted in and stable disease in 50% (8/16) of non-small cell lung cancer patients with CDKN2A loss (J Clin Oncol 32:5s, 2014 (suppl; abstr 8077)). detail...
CDKN2A loss renal cell carcinoma sensitive Palbociclib Preclinical Actionable In a preclinical study, renal cell carcinoma cell lines with CDKN2A loss were sensitive to Palbociclib (PD-0332991) (PMID: 23898052). 23898052
CDKN2A loss neuroendocrine tumor sensitive ZK304709 Preclinical Actionable In a preclinical study, an orthotopic mouse model treated with ZK 304709 demonstrated an 80% tumor growth reduction in neuroendocrine tumor cells with CDKN2A loss (PMID: 18829975). 18829975
CDKN2A loss pancreatic cancer decreased response GSK461364 + PD0332991 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of GSK461364 in pancreatic cancer cells with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss melanoma resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line deficient for CDKN2A demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
CDKN2A loss pancreatic cancer decreased response PD0332991 + Gemcitabine Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of Gemzar (gemcitabine) in pancreatic cancer cells with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss pancreatic cancer decreased response ON-01910 + PD0332991 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of ON-01910 in pancreatic cancer cell lines with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss brain glioblastoma multiforme sensitive Milciclib Preclinical - Cell line xenograft Actionable In a preclinical study, Milciclib (PHA-848125AC) resulted in tumor regression in glioma cell line xenograft models with CDKN2A loss (PMID: 23347136). 23347136
CDKN2A loss Advanced Solid Tumor predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of multiple cancer cell lines harboring CDKN2A loss and in Cdkn2a-depleted transformed cells in culture (PMID: 26140595). 26140595
CDKN2A loss chordoma sensitive Abemaciclib Preclinical - Cell culture Actionable In a preclinical study, Abemaciclib (LY2835219) inhibited growth of chordoma cell lines with CDKN2A loss and loss of p16 protein expression in culture (PMID: 26183925). 26183925
CDKN2A loss melanoma sensitive Alvocidib Preclinical Actionable In a preclinical study, melanoma cell lines with CDKN2A loss demonstrated a greater sensitivity to Alvocidib (flavopiridol) as compared to melanoma cell lines positive for CDKN2A (PMID: 12777976). 12777976
CDKN2A loss melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with CDKN2A loss demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in inhibition of cell growth (PMID: 27488531). 27488531
CDKN2A loss chordoma sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, Ibrance (palbociclib) inhibited expression of phosphorylated Rb and growth of chordoma cell lines with CDKN2A loss and loss of p16 protein expression in culture (PMID: 26183925). 26183925
NRAS Q61K CDKN2A loss melanoma sensitive Palbociclib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). 22983396
NRAS Q61K CDKN2A loss melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640726 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). 26603897
CDKN2A loss KRAS wild-type non-small cell lung carcinoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, a squamous non-small cell lung carcinoma patient with KRAS wild-type and loss of CDKN2A demonstrated a partial response when treated with Abemaciclib (LY2835219) (PMID: 27217383). 27217383
CDKN2A loss NRAS mutant melanoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, Abemaciclib (LY2835219) resulted in a partial response in a melanoma patient with CDKN2A loss and NRAS mutation (PMID: 27217383). detail... 27217383
CDKN2A mutant pancreatic cancer not applicable N/A Guideline Risk Factor Germline mutations in CDKN2A results in familial malignant melanoma syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org). detail...
BRAF mut KRAS mut CDKN2A mut triple-receptor negative breast cancer resistant Trametinib Preclinical Actionable In a preclinical study, human triple negative breast cancer cells harboring mutant BRAF, KRAS, and CDKN2A were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
NRAS mut CDKN2A mut acute lymphocytic leukemia resistant Trametinib Preclinical Actionable In a preclinical study, human acute lymphoblastic leukemia cells harboring NRAS and CDKN2A mutations were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
PIK3CA mutant CDKN2A mutant breast cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, a breast cancer cell line harboring mutations in PIK3CA and CDKN2A demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). 25261369
CDKN2A mut MET del exon14 PDGFRA mut SMAD4 Q249H melanoma sensitive Imatinib + Carboplatin + Paclitaxel Clinical Study Actionable In a clinical study, a melanoma patient harboring a PDGFRA mutation, CDKN2A mutation, MET exon 14 splice site mutation, and SMAD4 Q249H demonstrated a 21 month overall survival when treated with a combination of Gleevec (imatinib), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28514312). 28514312
CDKN2A over exp SMARCB1 negative rhabdoid cancer decreased response Palbociclib Preclinical Actionable In a preclinical study, CDKN2A (p16) over expression was associated with decreased sensitivity to Ibrance (palbociclib) in a SMARCB1-negative malignant rhabdoid tumor cell line in culture (PMID: 21871868). 21871868