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| Cancer tissue or cell line types | Nucleotide change | Amino acid change | Mutation type/clinical prediction | Protein domain | Functional effects of KEAP1 mutant |
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| Breast cell line and ductal carcinoma | c.68G>A | p.C23Y | Missense/pathogenic | NTR | Repression of NRF2-dependent transcription activity and ubiquitination defects |
| Lung AC, lung SCC | c.212G>T | p.R71L | Missense/pathogenic | BTB | Wild-type behavior |
| Stomach AC | c.246G>T | p.Q82H | Missense/pathogenic | BTB | Impaired effect on NRF2 pathway activation |
| EOC | c.319T>C | p.F107L | Missense/pathogenic | BTB | Enhance the NRF2 nuclear localization and its transcription activity |
| BUC, EOC | c.347G>C | p.R116P | Missense/pathogenic | BTB | Enhance the NRF2 nuclear localization and its transcription activity |
| Lung AC, lung SCC | c.463G>T | p.V155F | Missense/pathogenic | BTB | Enhance the binding of KEAP1 to NRF2 and facilitate NRF2 ubiquitination |
| EOC | c.475G>A | p.A159T | Missense/pathogenic | BTB | Enhance the NRF2 nuclear localization and its transcription activity |
| Lung AC, lung SCC | c.499G>T | p.V167F | Missense/pathogenic | BTB | Weakly affect the bind of KEAP1 to NRF2 without suppressing the NRF2 activity |
| BTC | c.543_544insC | p.S181fs∗11 | Frameshift/NS | IVR | Induce the loss of KEAP1 repression activity on NRF2 |
| HCC | c.548A>G | p.N183S | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| Lung AC | c.556G>C | p.G186R | Missense/pathogenic | IVR | Induce an enhanced binding of KEAP1 to NRF2 and facilitate its ubiquitination without suppressing NRF2-mediated transcription |
| EOC | c.563C>T | p.A188V | Missense/pathogenic | IVR | Enhance activation of NRF2 pathway and an increase of its transcriptional activity and nuclear localization |
| Lung AC | c.599A>C | p.H200P | Missense/pathogenic | IVR | Wild-type behavior |
| Lung SCC | c.671C>A | p.S224Y | Missense/pathogenic | IVR | Wild-type behavior |
| Lung SCC | c.691C>G | p.L231V | Missense/pathogenic | IVR | Wild-type behavior |
| Stomach AC | c.698G>A | p.S233N | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| CESC, colorectal AC | c.700C>T | p.R234W | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| Lung AC | c.706G>C | p.D236H | Missense/pathogenic | IVR | Reduce KEAP1-mediated repression of NRF2 |
| Lung SCC, liver | c.706G>T | p.D236Y | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| Lung AC | c.711delG | p.L237fs∗1 | Frameshift (stop codon)/NS | IVR | Reduce KEAP1-mediated repression of NRF2 |
| Lung AC | c.724G>A | p.E242K | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| Lung SCC | c.728C>G | p.S243C | Missense/pathogenic | IVR | Induce an enhanced binding of KEAP1 to NRF2 and facilitate its ubiquitination without suppressing NRF2-mediated transcription |
| BUC, lung AC | c.730G>A | p.E244K | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| BTC, stomach | c.746G>A | p.C249Y | Missense/pathogenic | IVR | Mutant KEAP1 fails to repress NRF2-dependent transactivation |
| Breast AC | c.767A>G | p.D256G | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| PF | c.790G>A | p.V264I | Missense/pathogenic | IVR | Reduce KEAP1-mediated repression of NRF2 |
| Lung AC | c.814C>T | p.R272C | Missense/pathogenic | IVR | Reduce KEAP1-mediated repression of NRF2 (impaired Nrf2 degradation) |
| Stomach AC | c.838T>C | p.F280L | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| Stomach AC | c.842T>C | p.L281P | Missense/pathogenic | IVR | Induce an impaired binding of KEAP1 to the CUL3 ubiquitin ligase |
| Lung AC, lung LCC | c.851A>T | p.Q284L | Missense/pathogenic | IVR | Reduce KEAP1-mediated repression of NRF2 |
| Stomach AC | c.863G>A | p.C288Y | Missense/pathogenic | IVR | Induce and impair binding of KEAP1 to NRF2 and facilitate NRF2 ubiquitination and its degradation |
| Lung AC, liver | c.880G>T | p.D294Y | Missense/pathogenic | IVR | Lead to deleterious effect on protein stability |
| Lung SCC | c.953C>T | p.P318L | Missense/pathogenic | KELCH1 | Wild-type behavior |
| Lung SCC | c.? | p.P318_fs | Frameshift/NS | KELCH1 | Impact on the KEAP1-NRF2 association and NRF2 degradation |
| EOC | c.1234C>T | p.P319S | Missense/NS | KELCH1 | Enhance activation of NRF2 pathway and an increase of its transcriptional activity and nuclear localization |
| Lung SCC | c.959G>A | p.R320Q | Missense/pathogenic | KELCH1 | Induce an enhanced binding of KEAP1 to NRF2 and facilitate its ubiquitination without suppressing NRF2-mediated transcription |
| Lung AC, lung SCC | c.965C>T | p.P322L | Missense/pathogenic | KELCH1 | Lead to deleterious effects on KEAP1 protein stability |
| Colorectal AC | c.989C>T | p.T330I | Missense/pathogenic | KELCH1 | Impair the KEAP1 binding to NRF2 through the KEAP1 DC pocket (lower affinity) |
| Lung AC | c.994G>T | p.G332C | Missense/pathogenic | KELCH1 | Induce an enhancement of the NRF2 activity |
| Gallbladder | c.996_996delC | p.G332fs∗67 | Frameshift/NS | KELCH1 | Lead a loss of NRF2 repression by KEAP1 |
| Lung AC | c.997G>T | p.G333C | Missense/pathogenic | KELCH1 | Induce misfolding effects and decrease the KEAP1 stability and capability to bind NRF2 |
| Lung | c.1001>T | p.Y334F | Missense/NS | KELCH1 | Disrupt the integrity of the Kelch domain of KEAP1 |
| HCC | c.1007G>A | p.R336Q | Missense/pathogenic | KELCH1 | Impair the KEAP1 binding to NRF2 through the KEAP1 DC pocket (lower affinity) |
| Gallbladder AC, breast AC | c.1013C>T | p.S338L | Missense/pathogenic | KELCH1 | Mutant KEAP1 fails to repress NRF2-dependent transactivation |
| HCC | c.1024C>A | p.L342M | Missense/pathogenic | KELCH1 | Impair the KEAP1 binding to NRF2 through the KEAP1 DC pocket (lower affinity) |
| Lung AC | c.1036InsT | p.S346_fs | Frameshift (stop codon)/pathogenic | KELCH1 | Lead to a premature termination and truncated KEAP1 protein |
| PF | c.1043insG | p.348_fs | Frameshift (stop codon)/NS | KELCH1 | Result in a frameshift and produce a truncated KEAP1 protein, with a lower KEAP1-mediated repression of NRF2 |
| Lung AC, stomach cell lines | c.1048G>A | p.G350S | Missense/NS | KELCH1 | Reduce KEAP1-mediated repression of NRF2 |
| Prostate | c.1069G>A | p.D357N | Missense/pathogenic | KELCH1 | Impair the KEAP1 binding to NRF2 through the KEAP1 DC pocket (lower affinity) |
| Colorectal AC | c.1075C>T | p.Q359X | Nonsense/pathogenic | KELCH1 | Impair the KEAP1 binding to NRF2 through the KEAP1 DC pocket (lower affinity) |
| Lung AC samples and cell lines | c.1090G>T | p.G364C | Missense/pathogenic | KELCH2 | Abolish the KEAP1-NRF2 interaction |
| Lung AC | c.GCC1098TTA | p.L367_fs | Frameshift/pathogenic | KELCH2 | Produce a truncated KEAP1 protein |
| Lung AC | c.1106T>C | p.V369A | Missense/pathogenic | KELCH2 | Lead to deleterious effects on KEAP1 protein stability |
| Gallbladder AC, HCC | c.1136G>A | p.G379D | Missense/pathogenic | KELCH2 | Mutant KEAP1 fails to repress NRF2-dependent transactivation. Induce a misfolding effects on the KEAP1 protein and decrease its ability to bind NRF2 |
| Lung AC | c.1238G>T | p.L413R | Missense/pathogenic | KELCH3 | Mutant KEAP1 fails to repress NRF2-dependent transactivation. Induce misfolding effects on the KEAP1 protein and decrease its ability to bind NRF2 |
| Lung AC | c.DelGG? | p.L413_fs | Frameshift (stop codon)/NS | KELCH3 | Reduce KEAP1-mediated repression of NRF2 |
| Lung AC | c.1243C>G | p.R415G | Missense/pathogenic | KELCH3 | Affect the ability of KEAP1 to repress NRF2 and lost the ability to bind and sequester NRF2 in the cytoplasm |
| Lung SCC, ESCC | c.1264G>A | p.D422N | Missense/pathogenic | KELCH3 | Enhance the binding of KEAP1 to NRF2 and facilitate NRF2 ubiquitination |
| Lung AC, lung SCC | c.1268G>T | p.G423V | Missense/pathogenic | KELCH3 | Enhance the binding of KEAP1 to NRF2 and facilitate NRF2 ubiquitination |
| Lung AC | c.1280C>T | p.A427V | Missense/pathogenic | KELCH3 | Reduce KEAP1-mediated NRF2 repression ability but Kelch domain should still be able to interact effectively with the ETGE and the DLG sites of NRF2 |
| Lung AC | c.1288G>T | p.G430C | Missense/pathogenic | KELCH3 | Induce a misfolding effect on the KEAP1 protein and decrease its ability to bind NRF2 and sequester NRF2 in the cytoplasm. |
| Lung AC cell line | c.1329T>G | p.Y443_fs | Frameshift (stop codon)/NS | KELCH3 | Reduce KEAP1-mediated repression of NRF2 |
| Lung AC | c.1370delG | p.L457fs∗1 | Frameshift (stop codon)/NS | KELCH3 | Result in a frameshift and produce a truncated KEAP1 protein, with a lower KEAP1-mediated repression of NRF2 |
| Lung AC | c.1396G>C | p.A466P | Missense/pathogenic | KELCH4 | Lead to deleterious effects on KEAP1 protein stability |
| Lung SCC | c.? | p.N469fs | Frameshift/NS | KELCH4 | Impact on the KEAP1-NRF2 association and the KEAP1 ability to suppress NRF2 |
| Lung AC, lung SCC, ESCC, UADT | c.1408C>T | p.R470C | Missense/pathogenic | KELCH4 | Exhibit enhanced binding to NRF2 and facilitate NRF2 ubiquitination |
| Lung LCC | c.1426G>A | p.G476R | Missense/NS | KELCH4 | Induce a misfolding effect on the KEAP1 protein and decrease its ability to bind NRF2 and sequester NRF2 in the cytoplasm. |
| Lung SCC | c.1438G>T | p.G480W | Missense/pathogenic | KELCH4 | Reduce the KEAP1-NRF2 binding |
| Lung AC | c.1448G>A | p.R483H | Missense/pathogenic | KELCH4 | Reduce the KEAP1-NRF2 binding |
| Lung AC | c.1477G>C | p.E493Q | Missense/pathogenic | KELCH4 | Induce an upregulation of the NRF2 activity |
| Lung SCC | c.1632G>T | p.W544C | Missense/pathogenic | KELCH5 | Reduce the KEAP1-NRF2 binding |
| Liver, lung AC | c.1661G>A | p.R554Q | Missense/pathogenic | KELCH6 | Reduce the KEAP1-NRF2 binding |
| Liver | c.1662G>A | p.W554X | Missense/pathogenic | KELCH6 | Decrease the NRF2 repression activity |
| PF | c.1663_1680del18 | p.S555_T560del | In frame/NS | KELCH6 | Reduce KEAP1-mediated repression of NRF2 |
| Lung AC | c.1709G>T | p.G570V | Missense/pathogenic | KELCH6 | Reduce the KEAP1-NRF2 binding |
| Lung AC | c.1772G>T | p.W591L | Missense/pathogenic | KELCH6 | Impair the KEAP1 binding to NRF2 through the KEAP1 DC pocket (lower affinity) |
| Colorectal AC | c.1816G>A | p.V606M | Missense/pathogenic | CTR | Induce an upregulation of the NRF2 activity |
| EOC | c.1831G>A | p.E611K | Missense/pathogenic | CTR | Enhance activation of NRF2 pathway and an increase of its transcriptional activity and nuclear localization |
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