KEAP1 (Q14145) variants and mutations
KEAP1 (also known as Q14145) is a human protein-coding gene encoding a kelch-like ECH-associated protein 1 protein. It continuously targets NRF2 for degradation under basal conditions but releases this brake when reactive electrophiles or oxidative stress modify KEAP1. Somatic loss-of-function variants can lock tumors into a persistent antioxidant state that promotes survival and treatment resistance. This analysis covers 3,139 KEAP1 variants and mutations. Of these, 25% have computational variant effect predictions. Disease context includes multiple sclerosis, lung adenocarcinoma, and relapsing-remitting multiple sclerosis. Example KEAP1 variants include Q2*, Q2E, and Q2H.
Variant analysis overview
- Gene: KEAP1
- Protein: Q14145
- UniProt accession: Q14145
- Organism: Homo sapiens
- Variants analyzed: 3139
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 3,015 unspecified-consequence records; 94 synonymous variants; 1 in-frame deletions; 19 missense variants; 5 splice-region variants; 3 frameshift variants; 2 substitution
- Prediction scores: 793 variants have prediction scores (25% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: multiple sclerosis, lung adenocarcinoma, relapsing-remitting multiple sclerosis, non-small cell lung carcinoma, squamous cell lung carcinoma, psoriasis, hepatocellular carcinoma, immune system disorder, neurodegenerative disease, lung carcinoma, lung large cell carcinoma, Familial multinodular goiter.
Protein structure and variant hotspots
- Protein features: 2 domains; 12 post-translational modification sites.
- Structural context: 839 variants have structural context.
- PTM context: 54 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable KEAP1 variants
Examples include Q2*, Q2E, Q2H, Q2L, Q2R, P3A, P3L, P3R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- Q2* (p.Gln2Ter), Ensembl rs2144631782, CADD 36.00
- Q2E (p.Gln2Glu), Ensembl rs2144631782
- Q2H (p.Gln2His), Ensembl rs2144631748, REVEL 0.16, CADD 19.40
- Q2L (p.Gln2Leu), Ensembl rs2144631773
- Q2R (p.Gln2Arg), Ensembl rs2144631773, REVEL 0.22, CADD 21.70
- P3A (p.Pro3Ala), Ensembl rs2144631740
- P3L (p.Pro3Leu), rs1914987906, ClinGen CA403999509, ClinVar RCV004409227, gnomAD rs1914987906, REVEL 0.11, CADD 22.30, Uncertain significance, not specified
- P3R (p.Pro3Arg), gnomAD rs1914987906, Uncertain significance
- P3S (p.Pro3Ser), Ensembl rs2144631740, REVEL 0.09, CADD 17.20
- D4A (p.Asp4Ala), Ensembl rs2144631703
- D4E (p.Asp4Glu), Ensembl rs2144631691
- D4G (p.Asp4Gly), Ensembl rs2144631703, REVEL 0.24, CADD 15.10
- D4H (p.Asp4His), cosmic curated COSV50266, Ensembl rs2144631713
- D4N (p.Asp4Asn), Ensembl rs2144631713
- D4V (p.Asp4Val), Ensembl rs2144631703
- D4Y (p.Asp4Tyr), cosmic curated COSV10584, REVEL 0.14, CADD 19.20
- P5A (p.Pro5Ala), Ensembl rs2144631676
- P5L (p.Pro5Leu), Ensembl rs2144631658
- P5R (p.Pro5Arg), Ensembl rs2144631658
- P5S (p.Pro5Ser), Ensembl rs2144631676
- R6K (p.Arg6Lys), Ensembl rs2144631625
- R6M (p.Arg6Met), Ensembl rs2144631625, REVEL 0.17, CADD 11.00
- R6S (p.Arg6Ser), Ensembl rs2144631608, CADD 3.98
- R6T (p.Arg6Thr), Ensembl rs2144631625
- R6W (p.Arg6Trp), cosmic curated COSV50635
- P7A (p.Pro7Ala), TOPMed rs1914987783, REVEL 0.09, CADD 15.90
- P7R (p.Pro7Arg), cosmic curated COSV10605, Ensembl rs2144631582
- P7S (p.Pro7Ser), TOPMed rs1914987783
- P7T (p.Pro7Thr), TOPMed rs1914987783
- S8C (p.Ser8Cys), Ensembl rs2144631555
- S8G (p.Ser8Gly), Ensembl rs2144631555
- S8N (p.Ser8Asn), rs746950247, ExAC rs746950247, gnomAD rs746950247, REVEL 0.12, CADD 22.20, Variant assessed as somatic; moderate impact.
- S8R (p.Ser8Arg), ExAC rs758239745, TOPMed rs758239745, gnomAD rs758239745, cosmic curated COSV50262
- S8T (p.Ser8Thr), ExAC rs746950247, gnomAD rs746950247
- G9A (p.Gly9Ala), Ensembl rs2144631498
- G9E (p.Gly9Glu), Ensembl rs2144631498, REVEL 0.06, CADD 18.70
- G9R (p.Gly9Arg), 1000Genomes rs187892356, ExAC rs187892356, TOPMed rs187892356, gnomAD rs187892356, REVEL 0.08, CADD 6.25
- G9V (p.Gly9Val), Ensembl rs2144631498
- G9W (p.Gly9Trp), 1000Genomes rs187892356, ExAC rs187892356, TOPMed rs187892356, gnomAD rs187892356, REVEL 0.21, CADD 15.10
- A10T (p.Ala10Thr), ExAC rs757488752, TOPMed rs757488752, gnomAD rs757488752, REVEL 0.09, CADD 18.90
- G11A (p.Gly11Ala), Ensembl rs956532438, REVEL 0.09, CADD 13.80
- G11R (p.Gly11Arg), Ensembl rs2144631446, cosmic curated COSV50270
- G11V (p.Gly11Val), Ensembl rs956532438, REVEL 0.10, CADD 15.80
- G11W (p.Gly11Trp), Ensembl rs2144631446
- A12G (p.Ala12Gly), TOPMed rs1914986363
- A12P (p.Ala12Pro), TOPMed rs1914986474
- A12S (p.Ala12Ser), cosmic curated COSV50645, TOPMed rs1914986474, REVEL 0.10, CADD 15.40
- A12T (p.Ala12Thr), TOPMed rs1914986474, REVEL 0.09, CADD 16.80
- A12V (p.Ala12Val), TOPMed rs1914986363
- C13F (p.Cys13Phe), Ensembl rs2144631359, REVEL 0.07, CADD 13.70
- C13R (p.Cys13Arg), Ensembl rs2144631371, REVEL 0.08, CADD 16.60
- C13S (p.Cys13Ser), Ensembl rs2144631359
- C13W (p.Cys13Trp), Ensembl rs2144631348
- C13Y (p.Cys13Tyr), cosmic curated COSV50261, Ensembl rs2144631359, REVEL 0.06, CADD 13.60
- C14F (p.Cys14Phe), Ensembl rs2144631318, REVEL 0.07, CADD 12.70
- C14R (p.Cys14Arg), Ensembl rs2144631334
- C14S (p.Cys14Ser), Ensembl rs2144631318
- C14W (p.Cys14Trp), Ensembl rs2144631309
- C14Y (p.Cys14Tyr), Ensembl rs2144631318
- R15* (p.Arg15Ter), cosmic curated COSV50648, ExAC rs764282924, TOPMed rs764282924, gnomAD rs764282924, CADD 33.00
- R15L (p.Arg15Leu), cosmic curated COSV50264, 1000Genomes rs144429440, ESP rs144429440, ExAC rs144429440, REVEL 0.08, CADD 17.90, Uncertain significance
- R15P (p.Arg15Pro), 1000Genomes rs144429440, ESP rs144429440, ExAC rs144429440, TOPMed rs144429440, Uncertain significance
- R15Q (p.Arg15Gln), rs144429440, ClinGen CA9195714, cosmic curated COSV50285, ClinVar RCV004184245, REVEL 0.05, CADD 14.30, Uncertain significance, not specified
- F16C (p.Phe16Cys), Ensembl rs2144631241
- F16I (p.Phe16Ile), Ensembl rs2144631251
- F16L (p.Phe16Leu), Ensembl rs2144631229
- F16V (p.Phe16Val), Ensembl rs2144631251
- F16Y (p.Phe16Tyr), Ensembl rs2144631241
- L17P (p.Leu17Pro), ExAC rs753277984, TOPMed rs753277984, gnomAD rs753277984
- L17Q (p.Leu17Gln), ExAC rs753277984, TOPMed rs753277984, gnomAD rs753277984, REVEL 0.23, CADD 24.20
- L17R (p.Leu17Arg), ExAC rs753277984, TOPMed rs753277984, gnomAD rs753277984
- L17V (p.Leu17Val), Ensembl rs2144631221
- P18A (p.Pro18Ala), TOPMed rs1409836286, gnomAD rs1409836286
- P18L (p.Pro18Leu), Ensembl rs2144631166, REVEL 0.21, CADD 21.70
- P18R (p.Pro18Arg), Ensembl rs2144631166
- P18T (p.Pro18Thr), TOPMed rs1409836286, gnomAD rs1409836286, REVEL 0.29, CADD 19.80
- Q20* (p.Gln20Ter), NCI-TCGA Cosmic COSV5030, cosmic curated COSV50309, Ensembl rs2144631097, CADD 25.50, Variant assessed as somatic; high impact.
- Q20E (p.Gln20Glu), Ensembl rs2144631097
- Q20H (p.Gln20His), 1000Genomes rs528129279, ExAC rs528129279, TOPMed rs528129279, gnomAD rs528129279, REVEL 0.09, CADD 5.76
- S21* (p.Ser21Ter), cosmic curated COSV50354, CADD 35.00
- S21A (p.Ser21Ala), Ensembl rs2144631071
- S21L (p.Ser21Leu), TOPMed rs1914985027, REVEL 0.18, CADD 23.60
- S21P (p.Ser21Pro), Ensembl rs2144631071
- S21T (p.Ser21Thr), Ensembl rs2144631071
- Q22* (p.Gln22Ter), ExAC rs766749491, gnomAD rs766749491, CADD 32.00
- Q22E (p.Gln22Glu), ExAC rs766749491, gnomAD rs766749491
- Q22H (p.Gln22His), Ensembl rs2144631012
- Q22K (p.Gln22Lys), ExAC rs766749491, gnomAD rs766749491, REVEL 0.09, CADD 6.34
- Q22L (p.Gln22Leu), Ensembl rs1914984781
- Q22R (p.Gln22Arg), Ensembl rs1914984781, REVEL 0.05, CADD 15.40
- C23* (p.Cys23Ter), Ensembl rs2144630950
- C23F (p.Cys23Phe), cosmic curated COSV10581, Ensembl rs2144630961, REVEL 0.03, CADD 18.50
- C23G (p.Cys23Gly), Ensembl rs2144630989, REVEL 0.04, CADD 10.70
- C23S (p.Cys23Ser), Ensembl rs2144630961
- C23W (p.Cys23Trp), Ensembl rs2144630950
- C23Y (p.Cys23Tyr), NCI-TCGA Cosmic COSV5028, cosmic curated COSV50284, Ensembl rs2144630961, UniProt VAR 036084, Uncertain significance, in a breast cancer sample
- P24A (p.Pro24Ala), Ensembl rs2144630932
- P24H (p.Pro24His), Ensembl rs2144630920
- P24L (p.Pro24Leu), Ensembl rs2144630920, REVEL 0.19, CADD 23.20, Uncertain significance, not specified
- P24R (p.Pro24Arg), Ensembl rs2144630920
- P24S (p.Pro24Ser), Ensembl rs2144630932
- P24T (p.Pro24Thr), Ensembl rs2144630932
- E25* (p.Glu25Ter), Ensembl rs2144630896
- E25A (p.Glu25Ala), TOPMed rs1038198065
- E25D (p.Glu25Asp), Ensembl rs1914984424
- E25K (p.Glu25Lys), NCI-TCGA Cosmic COSV5026, cosmic curated COSV50265, NCI-TCGA Cosmic COSV5064, Ensembl rs2144630896, Variant assessed as somatic; moderate impact.
- E25Q (p.Glu25Gln), cosmic curated COSV50644, Ensembl rs2144630896
- G26A (p.Gly26Ala), Ensembl rs2144630820
- G26E (p.Gly26Glu), cosmic curated COSV10803, Ensembl rs2144630820
- G26R (p.Gly26Arg), ExAC rs761466505, gnomAD rs761466505, REVEL 0.31, CADD 21.90
- G26V (p.Gly26Val), Ensembl rs2144630820, REVEL 0.33, CADD 21.50
- G26W (p.Gly26Trp), ExAC rs761466505, gnomAD rs761466505
- A27P (p.Ala27Pro), TOPMed rs1181065854, gnomAD rs1181065854
- A27S (p.Ala27Ser), TOPMed rs1181065854, gnomAD rs1181065854, REVEL 0.06, CADD 1.49
- G28A (p.Gly28Ala), TOPMed rs1271014988, gnomAD rs1271014988
- G28E (p.Gly28Glu), TOPMed rs1271014988, gnomAD rs1271014988, REVEL 0.12, CADD 18.40
- G28R (p.Gly28Arg), Ensembl rs2144630748
- G28V (p.Gly28Val), TOPMed rs1271014988, gnomAD rs1271014988
- G28W (p.Gly28Trp), Ensembl rs2144630748
- D29E (p.Asp29Glu), ExAC rs746477922, TOPMed rs746477922, gnomAD rs746477922, REVEL 0.06, CADD 17.30
- D29G (p.Asp29Gly), Ensembl rs2144630689
- D29H (p.Asp29His), NCI-TCGA Cosmic COSV5026, NCI-TCGA Cosmic COSV9940, cosmic curated COSV99408, ExAC rs768189808, Variant assessed as somatic; moderate impact.
- D29N (p.Asp29Asn), cosmic curated COSV50267, ExAC rs768189808, gnomAD rs768189808, REVEL 0.07, CADD 17.40
- D29V (p.Asp29Val), Ensembl rs2144630689
- D29Y (p.Asp29Tyr), ExAC rs768189808, gnomAD rs768189808
- A30E (p.Ala30Glu), ESP rs138428670, ExAC rs138428670, TOPMed rs138428670, gnomAD rs138428670, REVEL 0.10, CADD 9.49, Uncertain significance
- A30G (p.Ala30Gly), ESP rs138428670, ExAC rs138428670, TOPMed rs138428670, gnomAD rs138428670, Uncertain significance
- A30S (p.Ala30Ser), ExAC rs537634437, TOPMed rs537634437, gnomAD rs537634437, REVEL 0.04, CADD 1.20
- A30T (p.Ala30Thr), cosmic curated COSV50262, ExAC rs537634437, TOPMed rs537634437, gnomAD rs537634437, REVEL 0.08, CADD 5.24
- A30V (p.Ala30Val), rs138428670, ClinGen CA9195702, ClinVar RCV004155751, ESP rs138428670, REVEL 0.10, CADD 14.00, Uncertain significance, not specified
- V31A (p.Val31Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V31L (p.Val31Leu), Ensembl rs1568401901, REVEL 0.03, CADD 14.30
- V31M (p.Val31Met), Ensembl rs1568401901, REVEL 0.05, CADD 16.00
- M32I (p.Met32Ile), Ensembl rs2144630549
- M32L (p.Met32Leu), Ensembl rs2144630566
- M32V (p.Met32Val), cosmic curated COSV99407, Ensembl rs2144630566
- Y33* (p.Tyr33Ter), 1000Genomes rs575186517, ExAC rs575186517, TOPMed rs575186517, gnomAD rs575186517, CADD 33.00
- Y33C (p.Tyr33Cys), cosmic curated COSV50296, Ensembl rs2144630515
- Y33D (p.Tyr33Asp), Ensembl rs2144630537
- Y33F (p.Tyr33Phe), Ensembl rs2144630515
- Y33H (p.Tyr33His), cosmic curated COSV50265, Ensembl rs2144630537
- Y33N (p.Tyr33Asn), Ensembl rs2144630537
- Y33S (p.Tyr33Ser), Ensembl rs2144630515
- A34D (p.Ala34Asp), cosmic curated COSV10957, CADD 8.09
- A34G (p.Ala34Gly), Ensembl rs2144630477
- A34P (p.Ala34Pro), ESP rs372654184, ExAC rs372654184, TOPMed rs372654184, gnomAD rs372654184, CADD 0.51
- A34T (p.Ala34Thr), cosmic curated COSV50281, ESP rs372654184, ExAC rs372654184, TOPMed rs372654184, REVEL 0.12, CADD 22.10
- A34V (p.Ala34Val), NCI-TCGA Cosmic COSV5064, cosmic curated COSV50641, Ensembl rs2144630477, REVEL 0.10, CADD 22.70, Variant assessed as somatic; moderate impact.
- S35A (p.Ser35Ala), Ensembl rs2144630453
- S35C (p.Ser35Cys), Ensembl rs2144630438
- S35F (p.Ser35Phe), NCI-TCGA TCGA novel, Ensembl rs2144630438, Variant assessed as somatic; moderate impact.
- S35I (p.Ser35Ile), cosmic curated COSV50261
- S35P (p.Ser35Pro), Ensembl rs2144630453
- S35T (p.Ser35Thr), NCI-TCGA TCGA novel, Ensembl rs2144630453, Variant assessed as somatic; moderate impact.
- T36A (p.Thr36Ala), cosmic curated COSV50637, REVEL 0.32, CADD 16.30
- T36I (p.Thr36Ile), Ensembl rs2144630406
- T36N (p.Thr36Asn), Ensembl rs2144630406, REVEL 0.21, CADD 21.90
- T36S (p.Thr36Ser), Ensembl rs2144630406
- E37* (p.Glu37Ter), cosmic curated COSV10876, Ensembl rs2144630375, CADD 37.00
- E37D (p.Glu37Asp), Ensembl rs2144630358
- E37G (p.Glu37Gly), TOPMed rs1465714155, gnomAD rs1465714155, REVEL 0.26, CADD 23.30
- E37K (p.Glu37Lys), Ensembl rs2144630375
- E37Q (p.Glu37Gln), Ensembl rs2144630375
- E37V (p.Glu37Val), TOPMed rs1465714155, gnomAD rs1465714155
- C38* (p.Cys38Ter), Ensembl rs2144630310
- C38F (p.Cys38Phe), ExAC rs778091974, gnomAD rs778091974
- C38G (p.Cys38Gly), Ensembl rs2144630340
- C38S (p.Cys38Ser), Ensembl rs2144630340
- C38W (p.Cys38Trp), Ensembl rs2144630310
- C38Y (p.Cys38Tyr), ExAC rs778091974, gnomAD rs778091974, REVEL 0.12, CADD 19.50
- K39M (p.Lys39Met), Ensembl rs2144630296
- K39R (p.Lys39Arg), Ensembl rs2144630296
- A40E (p.Ala40Glu), cosmic curated COSV10957, NCI-TCGA Cosmic COSV5027, TOPMed rs1173824866, gnomAD rs1173824866, Variant assessed as somatic; moderate impact.
- A40G (p.Ala40Gly), TOPMed rs1173824866, gnomAD rs1173824866
- A40P (p.Ala40Pro), Ensembl rs2144630275
- A40T (p.Ala40Thr), Ensembl rs2144630275
- A40V (p.Ala40Val), cosmic curated COSV50278, TOPMed rs1173824866, gnomAD rs1173824866, REVEL 0.27, CADD 26.50
- E41* (p.Glu41Ter), NCI-TCGA Cosmic COSV9940, cosmic curated COSV99407, Ensembl rs2144630229, Variant assessed as somatic; high impact.
- E41G (p.Glu41Gly), Ensembl rs2144630220
- E41K (p.Glu41Lys), NCI-TCGA Cosmic COSV9940, Ensembl rs2144630229, Variant assessed as somatic; moderate impact.
Public KEAP1 analysis runs
- KEAP1 analysis run — KEAP1 (3,139 variants) — completed 2026-08-18