BRAF
|
A762E
|
missense |
unknown |
BRAF A762E does not lie within any known functional domains of the Braf protein (UniProt.org). A762E has been demonstrated to confer secondary resistance to Egfr inhibitors in culture (PMID: 27478040), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Jan 2024). |
Y |
BRAF
|
G469S
|
missense |
gain of function |
BRAF G469S is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469S results in increased Erk phosphorylation (PMID: 27478040) and induces increased cell proliferation and cell viability compared to wild-type Braf in culture (PMID: 29533785). |
|
BRAF
|
H574N
|
missense |
no effect - predicted |
BRAF H574N lies within the protein kinase domain of the Braf protein (UniProt.org). H574N results in Erk phosphorylation similar to wild-type Braf in culture (PMID: 27478040), and therefore, is predicted to have no effect on Braf protein function. |
|
BRAF
|
H574Q
|
missense |
gain of function |
BRAF H574Q lies within the protein kinase domain of the Braf protein (UniProt.org). H574Q confers a gain of function to the Braf protein as indicated by increased Erk phosphorylation in culture and tumor formation in animal models, and confers resistance to Egfr inhibitors in culture (PMID: 27478040). |
Y |
BRAF
|
P367R
|
missense |
gain of function |
BRAF P367R does not lie within any known functional domains within the Braf protein (UniProt.org). P367R confers a gain of function to the Braf protein as indicated by increased Erk phosphorylation in culture and tumor formation in animal models, and demonstrates resistance to Egfr inhibitors in culture (PMID: 27478040). |
Y |
BRAF
|
R682W
|
missense |
unknown |
BRAF R682W lies within the protein kinase domain of the Braf protein (UniProt.org). R682W has been demonstrated to confer resistance to an EGFR inhibitor in the context of EGFR exon 19 deletions in cultured cells (PMID: 27478040), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Nov 2023). |
Y |
IDH2
|
K130del
|
deletion |
unknown |
IDH2 K130del results in the deletion of an amino acid of the Idh2 protein at amino acid 130 (UniProt.org). K130del is not associated with induction of tumor formation in mice (PMID: 27478040), but has not been fully biochemically characterized and therefore, its effect on Idh2 protein function is unknown. |
|
KEAP1
|
D389Y
|
missense |
loss of function - predicted |
KEAP1 D389Y lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). D389Y is predicted to lead to a loss of Keap1 protein function as indicated by partial inhibition of Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
D479G
|
missense |
loss of function |
KEAP1 D479G lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). D479G confers a loss of function to the Keap1 protein as demonstrated by impaired binding and ubiquitination of Ikk-beta and Nrf2, leading to increased NF-kappaB signaling in cultured cells (PMID: 19818716), and partial inhibition of Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
E117K
|
missense |
loss of function |
KEAP1 E117K lies within the BTB domain of the Keap1 protein (UniProt.org). E117K results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
E611D
|
missense |
loss of function - predicted |
KEAP1 E611D lies within Kelch repeat 6 of the Keap1 protein (UniProt.org). E611D inhibits Nfe2l2 (Nrf2) target gene expression to similar levels of wild-type Keap1 in culture (PMID: 27478040), but fails to bind and destabilize Sox9 in cultured cells (PMID: 33173725), and therefore, is predicted to lead to a loss of Keap1 protein function. |
|
KEAP1
|
G333C
|
missense |
loss of function |
KEAP1 G333C lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G333C confers a loss of function to the Keap1 protein as demonstrated by loss of Nfe2l2 inhibition and increased transcription of Nfe2l2 target genes (PMID: 24322982, PMID: 27478040), and failure to bind and ubiquitinate Ikk-beta in cultured cells (PMID: 19818716). |
|
KEAP1
|
G417R
|
missense |
loss of function |
KEAP1 G417R lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G417R results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
G419W
|
missense |
loss of function |
KEAP1 G419W lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G419W results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
G524C
|
missense |
loss of function |
KEAP1 G524C lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). G524C results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
G603W
|
missense |
loss of function |
KEAP1 G603W lies within Kelch repeat 6 of the Keap1 protein (UniProt.org). G603W results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040), and failure to bind and destabilize Sox9 in cultured cells (PMID: 33173725). |
|
KEAP1
|
L268P
|
missense |
loss of function - predicted |
KEAP1 L268P lies within the BACK domain of the Keap1 protein (UniProt.org). L268P is predicted to lead to a loss of Keap1 protein function as indicated by partial inhibition of Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
P278S
|
missense |
loss of function |
KEAP1 P278S lies within the BACK domain of the Keap1 protein (UniProt.org). P278S results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
R204P
|
missense |
loss of function |
KEAP1 R204P lies within the BACK domain of the Keap1 protein (UniProt.org). R204P confers a loss of function to the Keap1 protein as indicated by partial inhibition of Nfe2l2 (Nrf2) target gene expression in culture (PMID: 27478040), and failure to bind and destabilize Sox9 in cultured cells (PMID: 33173725). |
|
KEAP1
|
R470H
|
missense |
loss of function |
KEAP1 R470H lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). R470H results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 30150714, PMID: 27478040). |
|
KEAP1
|
R470S
|
missense |
loss of function |
KEAP1 R470S lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). R470S results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 30150714, PMID: 27478040). |
|
KEAP1
|
R601W
|
missense |
loss of function |
KEAP1 R601W lies within Kelch repeat 6 of the Keap1 protein (UniProt.org). R601W results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
S102L
|
missense |
loss of function - predicted |
KEAP1 S102L lies within the BTB domain of the Keap1 protein (UniProt.org). S102L is predicted to lead to a loss of Keap1 protein function as indicated by partial inhibition of Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
S144F
|
missense |
no effect - predicted |
KEAP1 S144F lies within the BTB domain of the Keap1 protein (UniProt.org). S144F inhibits Nfe2l2 (Nrf2) target gene transcription to similar levels of wild-type Keap1 in culture (PMID: 27478040), and therefore, is predicted to have no effect on Keap1 protein function. |
|
KEAP1
|
T142M
|
missense |
loss of function - predicted |
KEAP1 T142M lies within the BTB domain of the Keap1 protein (UniProt.org). T142M is predicted to lead to a loss of Keap1 protein function as indicated by partial inhibition of Nfe2l2 (Nrf2) target gene expression in cell lines in culture (PMID: 27478040). |
|
KEAP1
|
W497L
|
missense |
loss of function |
KEAP1 W497L lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). W497L results in a loss of Keap1 protein function as indicated by failure to inhibit Nfe2l2 (Nrf2) target gene expression in cell lines (PMID: 27478040), and failure to bind and destabilize Sox9 in cultured cells (PMID: 33173725). |
|
RB1
|
Y756C
|
missense |
unknown |
RB1 Y756C lies within domain B of the Rb1 protein (UniProt.org). Y756C has been identified in sequencing studies (PMID: 27478040), but has not been biochemically characterized and therefore, its effect on Rb1 protein function is unknown (PubMed, Nov 2023). |
|
STK11
|
G251F
|
missense |
unknown |
STK11 G251F lies within the protein kinase domain of the Stk11 protein (UniProt.org). G251F has been identified in sequencing studies (PMID: 27478040), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Oct 2023). |
|
STK11
|
G251V
|
missense |
unknown |
STK11 G251V lies within the protein kinase domain of the Stk11 protein (UniProt.org). G251V has been identified in sequencing studies (PMID: 27478040, PMID: 29066508), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Oct 2023). |
|
STK11
|
G56V
|
missense |
unknown |
STK11 G56V lies within the protein kinase domain of the Stk11 protein (UniProt.org). G56V has been identified in sequencing studies (PMID: 27478040, PMID: 34922300), but has not been biochemically characterized and therefore, its effect on Stk11 protein function is unknown (PubMed, Oct 2023). |
|