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Gene Symbol KEAP1
Synonyms INrf2 | KLHL19
Gene Description KEAP1, kelch like ECH associated protein 1, binds Nrf2 and targets it for ubiquitin-mediated degradation, thereby negatively regulating the downstream cytoprotective activity of Nrf2 (PMID: 24142871, PMID: 27263465, PMID: 28523248). KEAP1 loss-of-function mutations have been identified in several tumor types, including lung and liver cancers (PMID: 24142871, PMID: 27263465, PMID: 29615460).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
9817 19 19p13.2 NM_203500 Tumor suppressor (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A159P missense unknown KEAP1 A159P does not lie within any known functional domains of the Keap1 protein (UniProt.org). A159P has been identified in the scientific literature (PMID: 29625053), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
A191D missense unknown KEAP1 A191D lies within the BACK domain of the Keap1 protein (UniProt.org). A191D has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
A30T missense unknown KEAP1 A30T does not lie within any known functional domains of the Keap1 protein (UniProt.org). A30T has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
A321V missense unknown KEAP1 A321V does not lie within any known functional domains of the Keap1 protein (UniProt.org). A321V has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
A91T missense unknown KEAP1 A91T lies within the BTB domain of the Keap1 protein (UniProt.org). A91T has been identified in the scientific literature (PMID: 27852700), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
C23Y missense loss of function KEAP1 C23Y does not lie within any known functional domains of the Keap1 protein (UniProt.org). C23Y retains the ability to interact with Cul3 and mediate ubiquitination of Ikk-beta (PMID: 17822677, PMID: 19818716), but fails to mediate ubiquitination of Nfe2l2 in culture (PMID: 17822677), and therefore, is predicted to lead to a loss of Keap1 protein function.
C249* nonsense loss of function - predicted KEAP1 C249* results in a premature truncation of the Keap1 protein at amino acid 249 of 624 (UniProt.org). C249* has not been characterized, however, due to the effects of other truncation mutations downstream of C249 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
D173N missense no effect KEAP1 D173N does not lie within any known functional domains of the Keap1 protein (UniProt.org). D173N results in a similar decrease in Nfe2l2 target gene expression and reduction in cell survival following irradiation and hydrogen peroxide treatment to wild-type Keap1 in culture (PMID: 33071215).
D236H missense loss of function KEAP1 D236H lies within the BACK domain of the Keap1 protein (UniProt.org). D236H confers a loss of function to the Keap1 protein as demonstrated by loss of Nfe2l2 inhibition leading to nuclear localization of Nfe2l2 in culture (PMID: 17020408), and is associated increased proliferation and migration in culture, tumor growth in animal models, and acquired resistance to tyrosine kinase inhibitors (PMID: 29812969). Y
D236N missense unknown KEAP1 D236N lies within the BACK domain of the Keap1 protein (UniProt.org). D236N has been identified in sequencing studies (PMID: 23788652), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
D236V missense no effect KEAP1 D236V lies within the BACK domain of the Keap1 protein (UniProt.org). D236V results in a similar decrease in Nfe2l2 target gene expression and reduction in cell survival following irradiation and hydrogen peroxide treatment to wild-type Keap1 in culture (PMID: 33071215).
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).
D422N missense loss of function KEAP1 D422N lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). D422N 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), and increased binding to Nrf1 in culture (PMID: 30126895).
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).
D479H missense loss of function KEAP1 D479H lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). D479H confers a loss of function to the Keap1 protein as demonstrated by loss of Nrf2 inhibition leading to increased expression of Nrf2 target genes, colony formation, and cell migration in culture (PMID: 32576270).
D78N missense no effect KEAP1 D78N lies within the BTB domain of the Keap1 protein (UniProt.org). D78N results in a similar decrease in Nfe2l2 target gene expression and reduction in cell survival following irradiation and hydrogen peroxide treatment to wild-type Keap1 in culture (PMID: 33071215).
dec exp none no effect KEAP1 dec exp indicates decreased expression of the Keap1 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
E117* nonsense loss of function - predicted KEAP1 E117* results in a premature truncation of the Keap1 protein at amino acid 117 of 624 (UniProt.org). E117* has not been characterized, however, due to the effects of other truncation mutations downstream of E117 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
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).
E192* nonsense loss of function - predicted KEAP1 E192* results in a premature truncation of the Keap1 protein at amino acid 192 of 624 (UniProt.org). E192* has not been characterized, however, due to the effects of other truncation mutations downstream of E192 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E205* nonsense loss of function - predicted KEAP1 E205* results in a premature truncation of the Keap1 protein at amino acid 205 of 624 (UniProt.org). E205* has not been characterized, however, due to the effects of other truncation mutations downstream of E205 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E218Q missense unknown KEAP1 E218Q lies within the BACK domain of the Keap1 protein (UniProt.org). E218Q has been identified in the scientific literature (PMID: 24137397, PMID: 28581676), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
E218V missense unknown KEAP1 E218V lies within the BACK domain of the Keap1 protein (UniProt.org). E218V has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
E219* nonsense loss of function - predicted KEAP1 E219* results in a premature truncation of the Keap1 protein at amino acid 219 of 624 (UniProt.org). E219* has not been characterized, however, due to the effects of other truncation mutations downstream of E219 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E258* nonsense loss of function - predicted KEAP1 E258* results in a premature truncation of the Keap1 protein at amino acid 258 of 624 (UniProt.org). E258* has not been characterized, however, due to the effects of other truncation mutations downstream of E258 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E307* nonsense loss of function - predicted KEAP1 E307* results in a premature truncation of the Keap1 protein at amino acid 307 of 624 (UniProt.org). E307* has not been characterized, however, due to the effects of other truncation mutations downstream of E307 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E41* nonsense loss of function - predicted KEAP1 E41* results in a premature truncation of the Keap1 protein at amino acid 41 of 624 (UniProt.org). E41* has not been characterized, however, due to the effects of other truncation mutations downstream of E41 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E441* nonsense loss of function - predicted KEAP1 E441* results in a premature truncation of the Keap1 protein at amino acid 441 of 624 (UniProt.org). E441* has not been characterized, however, due to the effects of other truncation mutations downstream of E441 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E444* nonsense loss of function - predicted KEAP1 E444* results in a premature truncation of the Keap1 protein at amino acid 444 of 624 (UniProt.org). E444* results in increased Nrf2 nuclear localization and reduced production of reactive oxygen species in cultured cells (PMID: 32576270), and therefore, is predicted to lead to a loss of Keap1 protein function.
E449* nonsense loss of function - predicted KEAP1 E449* results in a premature truncation of the Keap1 protein at amino acid 449 of 624 (UniProt.org). E449* has not been characterized, however, due to the effects of other truncation mutations downstream of E449 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
E493Q missense no effect - predicted KEAP1 E493Q lies within kelch repeat 1 of the Keap1 protein (UniProt.org). E493Q results in Nfe2l2 binding affinity similar to wild-type Keap1 in an in vitro assay (PMID: 34229009) and therefore, is predicted to have no effect on Keap1 protein function.
E593* nonsense loss of function - predicted KEAP1 E593* results in a premature truncation of the Keap1 protein at amino acid 593 of 624 (UniProt.org). E593* has not been characterized, however, due to the effects of other truncation mutations downstream of E593 (PMID: 14764898), is predicted to lead to a loss of Keap1 protein function.
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.
F16L missense unknown KEAP1 F16L does not lie within any known functional domains of the Keap1 protein (UniProt.org). F16L has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
F174L missense loss of function KEAP1 F174L does not lie within any known functional domains of the Keap1 protein (UniProt.org). F174L confers a loss of function to the Keap1 protein as demonstrated by loss of Nrf2 inhibition leading to increased expression of Nrf2 target genes, colony formation, and cell migration in culture (PMID: 32576270).
G186R missense loss of function KEAP1 G186R lies within the BACK domain of the Keap1 protein (UniProt.org). G186R 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).
G186S missense unknown KEAP1 G186S lies within the BACK domain of the Keap1 protein (UniProt.org). G186S has not been characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Jan 2023).
G332C missense loss of function KEAP1 G332C lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G332C results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
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).
G333D missense loss of function - predicted KEAP1 G333D lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G333D results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in vitro assay (PMID: 30150714), and therefore, is predicted to result in a loss of Keap1 protein function.
G333F missense unknown KEAP1 G333F lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G333F has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
G333S missense loss of function KEAP1 G333S lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G333S results in a loss of NRF2-mediated repression, as demonstrated by luciferase reporter assay compared to wild-type Keap1 (PMID: 30150714), and fails to bind and destabilize Sox9 in cultured cells (PMID: 33173725).
G364C missense loss of function KEAP1 G364C lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G364C confers a loss of function to the Keap1 protein as demonstrated by failure to bind and ubiquitinate Ikk-beta (PMID: 19818716) and impaired Nrf2 binding and cytosolic sequestration, resulting in increased activation of Nrf2 targets in cultured cells (PMID: 16507366), and inability to repress Nrf2 activity in mouse models (PMID: 21177379).
G379V missense unknown KEAP1 G379V lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G379V has been identified in the scientific literature (PMID: 33211847), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
G417E missense loss of function - predicted KEAP1 G417E lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G417E results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in vitro assay (PMID: 30150714), and therefore, is predicted to result in a loss of Keap1 protein function.
G417K missense loss of function - predicted KEAP1 G417K lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G417K results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in vitro assay (PMID: 30150714), and therefore, is predicted to result in a loss of Keap1 protein function.
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).
G417V missense loss of function - predicted KEAP1 G417V lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G417V results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in-vitro assay (PMID: 30150714), and therefore, is predicted to result in a loss of Keap1 protein function.
G417W missense unknown KEAP1 G417W lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G471W has been identified in sequencing studies (PMID: 34590036), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
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).
G423V missense loss of function KEAP1 G423V lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). G423V 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), and increased binding to Nrf1 in culture (PMID: 30126895).
G430C missense loss of function KEAP1 G430C lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). G430C confers a loss of function to the Keap1 protein as demonstrated by failure to bind and ubiquitinate Ikk-beta (PMID: 19818716) and impaired Nrf2 binding and cytosolic sequestration, resulting in increased Nrf2 transcriptional activity in cultured cells (PMID: 16507366), and inability to repress Nrf2 activity in mouse models (PMID: 21177379).
G477A missense unknown KEAP1 G477A lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). G477A has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
G477S missense unknown KEAP1 G477S lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). G477S has been identified in the scientific literature (PMID: 29625053, PMID: 24138990), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
G480V missense unknown KEAP1 G480V lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). G480V has been identified in sequencing studies (J Thor Oncol 2018; 13(10), S987-S988), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
G480W missense loss of function KEAP1 G480W lies within Kelch 4 domain of the Keap1 protein (PMID: 24322982). G480W 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).
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).
G570* nonsense loss of function - predicted KEAP1 G570* results in a premature truncation of the Keap1 protein at amino acid 570 of 624 (UniProt.org). Q570* has not been characterized, however, due to the effects of other truncation mutations downstream of Q570 (PMID: 14764898), is predicted to lead to a loss of Keap1 protein function.
G603V missense unknown KEAP1 G603V lies within Kelch repeat 6 of the Keap1 protein (UniProt.org). G603V has been identified in sequencing studies (PMID: 29615460), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
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).
G9R missense no effect - predicted KEAP1 G9R does not lie within any known functional domains of the Keap1 protein (UniProt.org). G9R results in binding and ubiquitination of Ikk-beta and Nrf2 similar to wild-type Keap1 in cultured cells (PMID: 19818716), and therefore, is predicted to have no effect on Keap1 protein function.
H247* nonsense loss of function - predicted KEAP1 H247* results in a premature truncation of the Keap1 protein at amino acid 247 of 624 (UniProt.org). H247* results in increased Nfe2l2 activity in a reporter assay (PMID: 12145307), and therefore, is predicted to lead to a loss of Keap1 protein function.
H274L missense unknown KEAP1 H274L lies within the BACK domain of the Keap1 protein (UniProt.org). H274L results in binding and ubiquitination of Ikk-beta similar to wild-type Keap1, but demonstrates increased Nrf2 binding with reduced levels of Nrf2 ubiquitination in cultured cells (PMID: 19818716), and therefore, its effect on Keap1 protein function is unknown.
H311R missense loss of function KEAP1 H311R does not lie within any known functional domains of the Keap1 protein (UniProt.org). H311R results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
H96L missense unknown KEAP1 H96L lies within the BTB domain of the Keap1 protein (UniProt.org). H96L has been identified in sequencing studies (PMID: 22980975, PMID: 29100014), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
I125F missense unknown KEAP1 I125F lies within the BTB domain of the Keap1 protein (UniProt.org). I125F has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
inact mut unknown loss of function KEAP1 inact mut indicates that this variant results in a loss of function of the Keap1 protein. However, the specific amino acid change has not been identified.
K216_Q217del deletion unknown KEAP1 K216_Q217del results in the deletion of two amino acids in the BACK domain of the Keap1 protein from amino acids 216 to 217 (UniProt.org). K216_Q217del has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
K287* nonsense loss of function - predicted KEAP1 K287* results in a premature truncation of the Keap1 protein at amino acid 287 of 624 (UniProt.org). K287* has not been characterized, however, due to the effects of other truncation mutations downstream of K287 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
K323* nonsense loss of function - predicted KEAP1 K323* results in a premature truncation of the Keap1 protein at amino acid 323 of 624 (UniProt.org). K323* has not been characterized, however, due to the effects of other truncation mutations downstream of K323 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
K97* nonsense loss of function - predicted KEAP1 K97* results in a premature truncation of the Keap1 protein at amino acid 97 of 624 (UniProt.org). K97* has not been characterized, however, due to the effects of other truncation mutations downstream of K97 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
K97M missense unknown KEAP1 K97M lies within the BTB domain of the Keap1 protein (UniProt.org). K97M has been identified in the scientific literature (PMID: 31658955), but has not been biochemically characterized and therefore, its effect of Keap1 protein function is unknown (PubMed, Sep 2022).
L100P missense unknown KEAP1 L100P lies within the BTB domain of the Keap1 protein (UniProt.org). L100P has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
L115Q missense unknown KEAP1 L115Q lies within the BTB domain of the Keap1 protein (UniProt.org). L115Q has been identified in the scientific literature (PMID: 32571982), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Mar 2023).
L231V missense no effect - predicted KEAP1 L231V lies within the BACK domain of the Keap1 protein (UniProt.org). L231V suppresses NRF2-mediated transcription similar to wild-type Keap1 in a reporter assay (PMID: 24322982), and therefore, is predicted to have no effect on Keap1 protein function.
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).
loss unknown loss of function KEAP1 loss indicates loss of the KEAP1 gene, mRNA, and protein.
M110I missense unknown KEAP1 M110I lies within the BTB domain of the Keap1 protein (UniProt.org). M110I has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
M110V missense unknown KEAP1 M110V lies within the BTB domain of the Keap1 protein (UniProt.org). M110V has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
M283fs frameshift loss of function KEAP1 M283fs results in a change in the amino acid sequence of the Keap1 protein beginning at aa 283 of 624, likely resulting in premature truncation of the functional protein (UniProt.org). M283fs results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
M503K missense unknown KEAP1 M503K lies within Kelch repeat 4 of the Keap1 protein (UniProt.org). M503K has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
M550* nonsense loss of function - predicted KEAP1 M550* results in a premature truncation of the Keap1 protein at amino acid 550 of 624 (UniProt.org). M550* has not been characterized, however, due to the effects of other truncation mutations downstream of M550 (PMID: 14764898), is predicted to lead to a loss of Keap1 protein function.
mutant unknown unknown KEAP1 mutant indicates an unspecified mutation in the KEAP1 gene.
N469fs frameshift loss of function KEAP1 N469fs results in a change in the amino acid sequence of the Keap1 protein beginning at 469 of 624, likely resulting in a premature truncation of the functional protein (UniProt.org). N469fs 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).
P278L missense unknown KEAP1 P278L lies within the BACK domain of the Keap1 protein (UniProt.org). P278L has been identified in the scientific literature (PMID: 32571982), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
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).
P318L missense no effect - predicted KEAP1 P318L does not lie within any known functional domains of the Keap1 protein (UniProt.org). P318L suppresses NRF2-mediated transcription similar to wild-type Keap1 in a reporter assay (PMID: 24322982), and therefore, is predicted to have no effect on Keap1 protein function.
P445Qfs*13 frameshift loss of function - predicted KEAP1 P445Qfs*13 indicates a shift in the reading frame starting at amino acid 445 and terminating 13 residues downstream causing a premature truncation of the 624 amino acid Keap1 protein (UniProt.org). P445Qfs*13 has not been characterized, however, due to the effects of other truncation mutations downstream of P445 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
P455fs frameshift loss of function KEAP1 P455fs results in a change in the amino acid sequence of the Keap1 protein beginning at aa 455 of 624, likely resulting in premature truncation of the functional protein (UniProt.org). P455fs results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
Q193* nonsense loss of function - predicted KEAP1 Q193* results in a premature truncation of the Keap1 protein at amino acid 193 of 624 (UniProt.org). Q193* has not been characterized, however, due to the effects of other truncation mutations downstream of Q193 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
Q201* nonsense loss of function - predicted KEAP1 Q201* results in a premature truncation of the Keap1 protein at amino acid 201 of 624 (UniProt.org). Q201* has not been characterized, however, due to the effects of other truncation mutations downstream of Q201 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
Q265* nonsense loss of function - predicted KEAP1 Q265* results in a premature truncation of the Keap1 protein at amino acid 265 of 624 (UniProt.org). Q265* has not been characterized, however, due to the effects of other truncation mutations downstream of Q265 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
Q402* nonsense loss of function - predicted KEAP1 Q402* results in a premature truncation of the Keap1 protein at amino acid 402 of 624 (UniProt.org). Q402* has not been characterized, however, due to the effects of other truncation mutations downstream of Q402 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
Q530* nonsense loss of function - predicted KEAP1 Q530* results in a premature truncation of the Keap1 protein at amino acid 530 of 624 (UniProt.org). Q530* has not been characterized, however, due to the effects of other truncation mutations downstream of Q530 (PMID: 14764898), is predicted to lead to a loss of Keap1 protein function.
Q620del deletion unknown KEAP1 Q620del results in the deletion of an amino acid of the Keap1 protein at amino acid 620 (UniProt.org). Q620del has been identified in sequencing studies (PMID: 30317074, PMID: 29615460), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
Q75* nonsense loss of function - predicted KEAP1 Q75* results in a premature truncation of the Keap1 protein at amino acid 75 of 624 (UniProt.org). Q75* has not been characterized, however, due to the effects of other truncation mutations downstream of Q75 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
R135L missense loss of function KEAP1 R135L lies within the BTB domain of the Keap1 protein (UniProt.org). R135L results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
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).
R234P missense unknown KEAP1 R234P lies within the BACK domain of the Keap1 protein (UniProt.org). R234P has been identified in sequencing studies (PMID: 34476097), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Dec 2022).
R234W missense loss of function KEAP1 R234W lies within the BACK domain of the Keap1 protein (UniProt.org). R234W confers a loss of function to the Keap1 protein as demonstrated by loss of Nrf2 inhibition leading to increased expression of Nrf2 target genes, colony formation, and cell migration in culture (PMID: 32576270).
R260* nonsense loss of function - predicted KEAP1 R260* results in a premature truncation of the Keap1 protein at amino acid 260 of 624 (UniProt.org). R260* has not been characterized, however, due to the effects of other truncation mutations downstream of R260 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
R260L missense unknown KEAP1 R260L lies within the BACK domain of the Keap1 protein (UniProt.org). R260L has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R260Q missense unknown KEAP1 R260Q lies within the BACK domain of the Keap1 protein (UniProt.org). R260Q has been identified in sequencing studies (PMID: 28581676, PMID: 23797736), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R272C missense loss of function KEAP1 R272C lies within the BACK domain of the Keap1 protein (UniProt.org). R272C confers a loss of function to the Keap1 protein as demonstrated the inability to ubiquitinate and repress Nrf2 activity in cell culture (PMID: 21177379).
R272H missense unknown KEAP1 R272H lies within the BACK domain of the Keap1 protein (UniProt.org). R272H has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
R272P missense unknown KEAP1 R272P lies within the BACK domain of the Keap1 protein (UniProt.org). R272P has been identified in sequencing studies (PMID: 22980975, PMID: 30885352), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Feb 2023).
R320L missense unknown KEAP1 R320L does not lie within any known functional domains of the Keap1 protein (UniProt.org). R320L has been identified in sequencing studies (PMID: 30933438, PMID: 29615460), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R320M missense unknown KEAP1 R320M does not lie within any known functional domains of the Keap1 protein (UniProt.org). R320M has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R320P missense unknown KEAP1 R320P does not lie within any known functional domains of the Keap1 protein (UniProt.org). R320P has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R320Q missense loss of function KEAP1 R320Q does not lie within any known functional domains of the Keap1 protein (UniProt.org). R320Q confers a loss of function to the Keap1 protein as demonstrated by loss of Nfe2l2 inhibition leading to increased transcription of Nfe2l2 target genes (PMID: 24322982), and loss of Nrf2 inhibition leading to increased expression of Nrf2 target genes (PMID: 30126895, PMID: 32576270), elevated colony formation and cell migration in culture, and increased tumorigenesis in mouse models (PMID: 32576270).
R320W missense unknown KEAP1 R320W does not lie within any known functional domains of the Keap1 protein (UniProt.org). R320W has been identified in the scientific literature (PMID: 29615460), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R336* nonsense loss of function - predicted KEAP1 R336* results in a premature truncation of the Keap1 protein at amino acid 336 of 624 (UniProt.org). R336* has not been characterized, however, due to the effects of other truncation mutations downstream of R336 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
R362W missense loss of function KEAP1 R362W lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). R362W results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
R413L missense loss of function KEAP1 R413L lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). R413L confers a loss of function to the Keap1 protein as demonstrated by failure to bind and ubiquitinate Ikk-beta (PMID: 19818716), and loss of Nrf2 inhibition leading to increased expression of Nrf2 target genes, colony formation, and cell migration in culture (PMID: 32576270).
R415G missense loss of function KEAP1 R415G lies within Kelch repeat 2 of the Keap1 protein (UniProt.org). R415G results in the inability of Keap1 to repress Nrfl2 activity in cell culture (PMID: 25582950).
R460G missense unknown KEAP1 R460G lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). R460G has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R460S missense unknown KEAP1 R460S lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). R460S has been identified in sequencing studies (PMID: 23033341), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R470C missense loss of function KEAP1 R470C lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). R470C 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), and impaired degradation of Nrf2 in culture (PMID: 30126895).
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).
R470K missense loss of function - predicted KEAP1 R470K lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). R470K results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in vitro assay (PMID: 30150714), and therefore, is predicted to result in a loss of Keap1 protein function.
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).
R536H missense unknown KEAP1 R536H lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). R536H has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
R554Q missense loss of function KEAP1 R554Q lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). R554Q 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).
R601L missense unknown KEAP1 R601L lies within Kelch repeat 6 of the Keap1 protein (UniProt.org). R601L results in Nfe2l2 binding affinity similar to wild-type Keap1 in an in vitro assay (PMID: 34229009), but has not been fully biochemically characterized and therefore, its effect on Keap1 protein function is unknown.
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).
R71L missense no effect - predicted KEAP1 R71L does not lie within any known functional domains of the Keap1 protein (UniProt.org). R71L suppresses NRF2-mediated transcription similar to wild-type Keap1 in a reporter assay (PMID: 24322982), and therefore, is predicted to have no effect on Keap1 protein function.
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).
S104R missense unknown KEAP1 S104R lies within the BTB domain of the Keap1 protein (UniProt.org). S104R has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
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.
S224Y missense no effect - predicted KEAP1 S224Y lies within the BACK domain of the Keap1 protein (UniProt.org). S224Y suppresses NRF2-mediated transcription similar to wild-type Keap1 in a reporter assay (PMID: 24322982), and therefore, is predicted to have no effect on Keap1 protein function.
S243C missense loss of function KEAP1 S243C lies within the BACK domain of the Keap1 protein (UniProt.org). S243C 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), and impaired degradation of Nfe2l2 (PMID: 30126895).
S404* nonsense loss of function KEAP1 S404* results in a premature truncation of the Keap1 protein at amino acid 404 of 624 (UniProt.org). S404* 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).
S45F missense unknown KEAP1 S45F does not lie within any known functional domains of the Keap1 protein (UniProt.org). S45F has been identified in sequencing studies (PMID: 22348534), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
S45Y missense unknown KEAP1 S45Y does not lie within any known functional domains of the Keap1 protein (UniProt.org). S45Y has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
S580R missense unknown KEAP1 S580R lies within Kelch repeat 6 of the Keap1 protein (UniProt.org). S580R has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
S599* nonsense loss of function KEAP1 S599* results in a premature truncation of the Keap1 protein at amino acid 599 of 624 (UniProt.org). S599* results in a loss of Keap1 protein function as demonstrated by a loss of Nfe2l2 repression in a reporter assay, and aberrant localization of Nfe2l2 in culture (PMID: 14764898).
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).
V155A missense unknown KEAP1 V155A does not lie within any known functional domains of the Keap1 protein (UniProt.org). V155A has been identified in the scientific literature (PMID: 29625053), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
V155F missense loss of function KEAP1 V155F does not lie within any known functional domains of the Keap1 protein (UniProt.org). V155F 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).
V167F missense loss of function KEAP1 V167F does not lie within any known functional domains of the Keap1 protein (UniProt.org). V167F 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).
V214M missense unknown KEAP1 V214M lies within the BACK domain of the Keap1 protein (UniProt.org). V214M has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
V271L missense loss of function - predicted KEAP1 V271L lies within the BACK domain of the Keap1 protein (UniProt.org). V271L results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in vitro assay (PMID: 30150714), and therefore, is predicted to result in a loss of Keap1 protein function.
V271M missense loss of function KEAP1 V271M lies within the BACK domain of the Keap1 protein (UniProt.org). V271M results in a loss of NRF2-mediated repression compared to wild-type Keap1 in an in vitro assay (PMID: 30150714), and results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
V369A missense unknown KEAP1 V369A lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). V369A has been identified in the scientific literature (PMID: 29615460, PMID: 21610322), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
V453M missense no effect KEAP1 V453M lies within Kelch repeat 3 of the Keap1 protein (UniProt.org). V453M results in a similar decrease in Nfe2l2 target gene expression and reduction in cell survival following irradiation and hydrogen peroxide treatment to wild-type Keap1 in culture (PMID: 33071215).
W252C missense unknown KEAP1 W252C lies within the BACK domain of the Keap1 protein (UniProt.org). W252C has been identified in sequencing studies (PMID: 26599269), but has not been biochemically characterized and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
W497* nonsense loss of function - predicted KEAP1 W497* results in a premature truncation of the Keap1 protein at amino acid 497 of 624 (UniProt.org). W497* has not been characterized, however, due to the effects of other truncation mutations downstream of W497 (PMID: 14764898), is predicted to lead to a loss of Keap1 protein function.
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).
W544C missense loss of function KEAP1 W544C lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). W544C 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).
W544R missense unknown KEAP1 W544R lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). W544R has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
wild-type none no effect Wild-type KEAP1 indicates that no mutation has been detected within the KEAP1 gene.
Y141F missense unknown KEAP1 Y141F lies within the BTB domain of the Keap1 protein (UniProt.org). Y141F results in EGF-induced Keap1 phosphorylation similar to wild-type protein in culture (PMID: 25628777), but has not been fully biochemically characterized and therefore, its effect on Keap1 protein function is unknown.
Y345* nonsense loss of function - predicted KEAP1 Y345* results in a premature truncation of the Keap1 protein at amino acid 345 of 624 (UniProt.org). Y345* has not been characterized, however, due to the effects of other truncation mutations downstream of Y345 (PMID: 14764898, PMID: 24322982), is predicted to lead to a loss of Keap1 protein function.
Y490* nonsense loss of function KEAP1 Y490* results in a premature truncation of the Keap1 protein at amino acid 490 of 624 (UniProt.org). Y490* confers a loss of function to the Keap1 protein as demonstrated by loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene expression and cell survival following irradiation or hydrogen peroxide treatment in culture (PMID: 33071215).
Y520C missense unknown KEAP1 Y520C lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). Y520C has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
Y537H missense unknown KEAP1 Y537H lies within Kelch repeat 5 of the Keap1 protein (UniProt.org). Y537H has not been characterized in the scientific literature and therefore, its effect on Keap1 protein function is unknown (PubMed, Nov 2022).
Y584* nonsense loss of function - predicted KEAP1 Y584* results in a premature truncation of the Keap1 protein at amino acid 584 of 624 (UniProt.org). Y584* has not been characterized, however, due to the effects of other truncation mutations downstream of Y584 (PMID: 14764898), is predicted to lead to a loss of Keap1 protein function.