CHEK1 (O14757) variants and mutations
CHEK1 (also known as O14757) is a human protein-coding gene encoding a serine/threonine-protein kinase Chk1 protein. It enforces the replication-stress and DNA-damage checkpoints, stabilizing stalled replication forks and delaying cell-cycle progression until DNA can be repaired. Many cancers become dependent on CHK1 signaling under high replication stress, making it an anticancer target. This analysis covers 854 CHEK1 variants and mutations. Of these, 65% have computational variant effect predictions. Disease context includes neurodegenerative disease, oocyte/zygote/embryo maturation arrest 21, and Male infertility due to gonadal dysgenesis or sperm disorder. Example CHEK1 variants include M1?, A2G, and A2T.
Variant analysis overview
- Gene: CHEK1
- Protein: O14757
- UniProt accession: O14757
- Organism: Homo sapiens
- Variants analyzed: 854
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 625 unspecified-consequence records; 118 missense variants; 70 synonymous variants; 23 frameshift variants; 5 in-frame deletions; 9 stop-gained variants; 3 splice-region variants; 1 substitution
- Prediction scores: 557 variants have prediction scores (65% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, oocyte/zygote/embryo maturation arrest 21, Male infertility due to gonadal dysgenesis or sperm disorder, alopecia areata, hereditary neoplastic syndrome, Inherited cancer-predisposing syndrome, non-small cell lung carcinoma, breast cancer, acute myeloid leukemia, ovarian cancer, neoplasm, cancer.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 9 post-translational modification sites.
- Structural context: 550 variants have structural context.
- PTM context: 11 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, ClinGen, MaveDB, LitVar.
Notable CHEK1 variants
Examples include M1?, A2G, A2T, A2V, A2S, A2A, V3M, V3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5402, cosmic curated COSV54024, TOPMed rs1940631418, cosmic curated COSV10459, Variant assessed as somatic; high impact.
- A2G (p.Ala2Gly), ExAC rs757321404, gnomAD rs757321404, REVEL 0.22, CADD 23.50
- A2T (p.Ala2Thr), Ensembl rs2135968538
- A2V (p.Ala2Val), cosmic curated COSV54026, ExAC rs757321404, gnomAD rs757321404
- A2S (p.Ala2Ser), gnomAD 11-125625770-G-T, CADD 14.30
- A2A (p.Ala2Ala), gnomAD 11-125625772-C-G, CADD 2.69
- V3M (p.Val3Met), Ensembl rs2135968566, REVEL 0.18, CADD 13.20
- V3S (p.Val3Ser), rs1940631774, gnomAD 11-125626773-C-CA, CADD 31.00
- P4S (p.Pro4Ser), ExAC rs201459198, TOPMed rs201459198, gnomAD rs201459198, REVEL 0.18, CADD 15.10, Uncertain significance, not specified
- P4A (p.Pro4Ala), rs987393347, gnomAD 11-125625803-C-G, CADD 2.93
- P4P (p.Pro4Pro), gnomAD 11-125625805-C-T, CADD 4.79
- P4L (p.Pro4Leu), gnomAD 11-125626779-C-T, REVEL 0.35, CADD 22.90
- F5L (p.Phe5Leu), Ensembl rs2135968591
- F5S (p.Phe5Ser), rs1345632360, gnomAD 11-125625855-T-C, CADD 7.32
- F5Y (p.Phe5Tyr), rs1345632360, gnomAD 11-125625855-T-A, CADD 4.40
- V6A (p.Val6Ala), rs779205340, gnomAD 11-125625774-T-C, CADD 13.60
- V6V (p.Val6Val), rs1399750655, gnomAD 11-125625775-C-T, CADD 4.06
- V6G (p.Val6Gly), gnomAD 11-125626785-T-G, REVEL 0.43, CADD 28.80
- E7K (p.Glu7Lys), cosmic curated COSV54023
- D8E (p.Asp8Glu), TOPMed rs1940631878
- D8N (p.Asp8Asn), NCI-TCGA Cosmic COSV5402, cosmic curated COSV54021, Variant assessed as somatic; moderate impact.
- D8R (p.Asp8Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- W9* (p.Trp9Ter), gnomAD rs1940632258, CADD 31.00
- W9G (p.Trp9Gly), rs1940568056, gnomAD 11-125625850-AC-A, CADD 1.67
- W9R (p.Trp9Arg), rs1220819081, gnomAD 11-125625857-T-C, CADD 0.52
- W9C (p.Trp9Cys), gnomAD 11-125625859-G-T, CADD 12.60
- D10E (p.Asp10Glu), TOPMed rs1940632613, REVEL 0.22, CADD 22.40
- D10H (p.Asp10His), gnomAD rs1940632387, REVEL 0.50, CADD 14.70
- D10N (p.Asp10Asn), cosmic curated COSV10639
- D10A (p.Asp10Ala), rs769608055, gnomAD 11-125626796-G-GC, CADD 33.00
- L11I (p.Leu11Ile), gnomAD 11-125625776-C-A, CADD 12.20
- L11L (p.Leu11Leu), rs1392538873, gnomAD 11-125625778-T-C, CADD 6.00
- L11F (p.Leu11Phe), rs1391215861, gnomAD 11-125625785-C-T, CADD 13.80
- L11P (p.Leu11Pro), gnomAD 11-125625786-T-C, CADD 15.70
- V12L (p.Val12Leu), ExAC rs200520758, TOPMed rs200520758, gnomAD rs200520758, REVEL 0.15, CADD 24.60
- V12M (p.Val12Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V12C (p.Val12Cys), gnomAD 11-125626800-TG-T, CADD 31.00
- Q13* (p.Gln13Ter), Ensembl rs2135968703
- Q13Q (p.Gln13Gln), rs968832353, gnomAD 11-125625790-G-A, CADD 4.70
- Q13H (p.Gln13His), gnomAD 11-125626807-A-C, REVEL 0.12, CADD 19.80
- T14N (p.Thr14Asn), cosmic curated COSV54023
- L15Q (p.Leu15Gln), Ensembl rs2135968727, REVEL 0.71, CADD 25.70
- L15L (p.Leu15Leu), rs1940562913, gnomAD 11-125625802-C-A, CADD 0.66
- G16E (p.Gly16Glu), cosmic curated COSV10722, REVEL 0.76, CADD 27.70
- G16V (p.Gly16Val), NCI-TCGA Cosmic COSV9962, cosmic curated COSV99629, Variant assessed as somatic; moderate impact.
- G16R (p.Gly16Arg), rs980250476, gnomAD 11-125625794-G-C, CADD 9.86
- G16G (p.Gly16Gly), gnomAD 11-125625796-A-G, CADD 2.29
- E17K (p.Glu17Lys), Ensembl rs2135968735
- E17D (p.Glu17Asp), gnomAD 11-125626819-A-T, REVEL 0.23, CADD 24.40
- G18D (p.Gly18Asp), TOPMed rs1395953036, gnomAD rs1395953036
- G18N (p.Gly18Asn), cosmic curated COSV10512
- A19V (p.Ala19Val), Ensembl rs2135968764, CADD 11.90
- A19G (p.Ala19Gly), rs1229187837, gnomAD 11-125625816-C-G, CADD 10.60
- A19E (p.Ala19Glu), gnomAD 11-125625816-C-A, CADD 10.20
- A19A (p.Ala19Ala), rs772496915, gnomAD 11-125625817-A-G, CADD 7.40
- A19T (p.Ala19Thr), rs1485882936, gnomAD 11-125625818-G-A, CADD 0.05
- A19D (p.Ala19Asp), gnomAD 11-125625819-C-A, CADD 8.84
- Y20C (p.Tyr20Cys), gnomAD rs1350704599
- G21E (p.Gly21Glu), Ensembl rs1940633565
- G21R (p.Gly21Arg), cosmic curated COSV54023, ExAC rs751896993, TOPMed rs751896993, gnomAD rs751896993
- G21S (p.Gly21Ser), rs73616024, gnomAD 11-125625824-G-A, CADD 9.14
- G21D (p.Gly21Asp), rs1211698286, gnomAD 11-125625825-G-A, CADD 10.40
- G21G (p.Gly21Gly), rs1230607374, gnomAD 11-125625826-C-T, CADD 7.42
- G21W (p.Gly21Trp), rs1464699905, gnomAD 11-125625827-G-T, CADD 3.18
- G21A (p.Gly21Ala), rs1414692460, gnomAD 11-125625834-G-C, CADD 0.06
- G21V (p.Gly21Val), rs946157626, gnomAD 11-125625879-G-T, CADD 0.19
- E22D (p.Glu22Asp), cosmic curated COSV10584
- E22K (p.Glu22Lys), gnomAD 11-125626832-G-A, REVEL 0.41, CADD 22.40
- V23F (p.Val23Phe), gnomAD 11-125627608-G-T, REVEL 0.72, CADD 23.10
- V23V (p.Val23Val), gnomAD 11-125627610-T-A, CADD 20.20
- Q24K (p.Gln24Lys), Ensembl rs2135971921, REVEL 0.15, CADD 20.10
- Q24R (p.Gln24Arg), gnomAD 11-125625880-GC-G, CADD 12.10
- Q24* (p.Gln24Ter), rs777220059, gnomAD 11-125625881-C-T, CADD 34.00
- Q24E (p.Gln24Glu), gnomAD 11-125625881-C-G, CADD 6.45
- Q24Q (p.Gln24Gln), rs1404488857, gnomAD 11-125625883-G-A, CADD 1.62
- L25I (p.Leu25Ile), ExAC rs766554164, gnomAD rs766554164, REVEL 0.26, CADD 19.60
- L25W (p.Leu25Trp), gnomAD 11-125625818-GC-G, CADD 12.30
- L25M (p.Leu25Met), gnomAD 11-125625821-C-A, CADD 9.57
- L25P (p.Leu25Pro), rs1262483486, gnomAD 11-125625822-T-C, CADD 7.90
- L25F (p.Leu25Phe), gnomAD 11-125627614-C-T, REVEL 0.33, CADD 20.10
- L25V (p.Leu25Val), gnomAD 11-125627614-C-G, REVEL 0.27, CADD 19.70
- A26V (p.Ala26Val), Ensembl rs1565361701, REVEL 0.13, CADD 20.40
- A26G (p.Ala26Gly), gnomAD 11-125627618-C-G, REVEL 0.18, CADD 19.90
- A26A (p.Ala26Ala), rs751950235, gnomAD 11-125627619-T-C, CADD 18.80
- V27E (p.Val27Glu), cosmic curated COSV10722
- N28S (p.Asn28Ser), ExAC rs755282936, gnomAD rs755282936, REVEL 0.48, CADD 21.50
- N28T (p.Asn28Thr), ExAC rs755282936, gnomAD rs755282936
- N28D (p.Asn28Asp), rs1479690184, gnomAD 11-125625836-A-G, CADD 10.80
- N28N (p.Asn28Asn), rs1057440910, gnomAD 11-125625838-C-T, CADD 1.80
- R29G (p.Arg29Gly), rs1555067411, ClinGen CA383190150, ClinVar RCV000586016, Ensembl rs1555067411, Uncertain significance, not provided
- R29T (p.Arg29Thr), cosmic curated COSV54022
- R29W (p.Arg29Trp), gnomAD 11-125625764-C-T, CADD 17.60
- R29R (p.Arg29Arg), rs1472862428, gnomAD 11-125625764-C-A, CADD 7.19
- R29Q (p.Arg29Gln), rs1940559253, gnomAD 11-125625765-G-A, CADD 9.37
- R36del (p.Arg36del), rs756532713, gnomAD 11-125625860-AGCC, CADD 2.55
- R29C (p.Arg29Cys), rs544839853, gnomAD 11-125625863-C-T, CADD 0.03
- R29L (p.Arg29Leu), gnomAD 11-125625864-G-T, CADD 15.90
- R29H (p.Arg29His), rs1253603668, gnomAD 11-125625864-G-A, CADD 16.00
- R29K (p.Arg29Lys), gnomAD 11-125627627-G-A, REVEL 0.08, CADD 20.60
- V30I (p.Val30Ile), ExAC rs781671034, gnomAD rs781671034, REVEL 0.08, CADD 18.30
- V30V (p.Val30Val), rs1940675077, gnomAD 11-125627631-A-C, CADD 18.20
- T31I (p.Thr31Ile), gnomAD rs1191531722
- T31N (p.Thr31Asn), gnomAD rs1191531722, REVEL 0.26, CADD 19.90
- T31A (p.Thr31Ala), rs77183579, gnomAD 11-125625845-A-G, CADD 0.00
- T31K (p.Thr31Lys), gnomAD 11-125625846-C-A, CADD 1.33
- T31M (p.Thr31Met), rs1310128627, gnomAD 11-125625846-C-T, CADD 1.61
- T31T (p.Thr31Thr), rs762765107, gnomAD 11-125625847-G-A, CADD 1.53
- T31S (p.Thr31Ser), rs892092235, gnomAD 11-125625887-A-T, CADD 0.02
- T31R (p.Thr31Arg), gnomAD 11-125625888-C-G, CADD 6.91
- E32D (p.Glu32Asp), NCI-TCGA Cosmic COSV5402, cosmic curated COSV54022, Variant assessed as somatic; moderate impact.
- E33E (p.Glu33Glu), rs1479304104, gnomAD 11-125625877-G-A, CADD 5.98
- E33D (p.Glu33Asp), rs1479304104, gnomAD 11-125625877-G-C, CADD 14.70
- A34T (p.Ala34Thr), gnomAD rs1269445439, REVEL 0.30, CADD 21.00
- A34V (p.Ala34Val), Ensembl rs2135972027
- A34P (p.Ala34Pro), gnomAD 11-125627641-G-C, REVEL 0.57, CADD 20.70
- V35D (p.Val35Asp), Ensembl rs2135972061
- V35L (p.Val35Leu), TOPMed rs1380056031, gnomAD rs1380056031, REVEL 0.58, CADD 20.80
- V35V (p.Val35Val), rs1447578195, gnomAD 11-125627646-C-T, CADD 16.20
- A36S (p.Ala36Ser), ExAC rs753180922, gnomAD rs753180922, REVEL 0.69, CADD 20.40
- A36T (p.Ala36Thr), rs753180922, NCI-TCGA Cosmic COSV9962, cosmic curated COSV99629, ExAC rs753180922, REVEL 0.75, CADD 20.80, Variant assessed as somatic; moderate impact.
- V37M (p.Val37Met), Ensembl rs2135972101, REVEL 0.27, CADD 20.80
- V37G (p.Val37Gly), gnomAD 11-125627651-T-G, REVEL 0.76, CADD 21.40
- V37V (p.Val37Val), rs1940675965, gnomAD 11-125627652-G-A, CADD 18.90
- K38I (p.Lys38Ile), rs116191495, gnomAD 11-125625780-A-T, CADD 18.50
- K38K (p.Lys38Lys), rs1372882814, gnomAD 11-125625814-A-G, CADD 4.84
- K38N (p.Lys38Asn), rs1372882814, gnomAD 11-125625814-A-T, CADD 13.40
- K38* (p.Lys38Ter), gnomAD 11-125627650-GTGA, CADD 18.90
- I39T (p.Ile39Thr), cosmic curated COSV54025, ESP rs367942205, ExAC rs367942205, TOPMed rs367942205, REVEL 0.20, CADD 21.60
- I39F (p.Ile39Phe), gnomAD 11-125625839-A-T, CADD 5.55
- I39I (p.Ile39Ile), rs1591387955, gnomAD 11-125625841-C-T, CADD 1.32
- V40I (p.Val40Ile), Ensembl rs2135972150
- V40V (p.Val40Val), rs754190375, gnomAD 11-125627661-A-G, CADD 15.60
- D41G (p.Asp41Gly), TOPMed rs1940676649, REVEL 0.66, CADD 21.50
- D41N (p.Asp41Asn), cosmic curated COSV54022, ExAC rs778668643, TOPMed rs778668643, gnomAD rs778668643, REVEL 0.14, CADD 20.90
- D41A (p.Asp41Ala), rs925840558, gnomAD 11-125625885-A-C, CADD 2.11
- D41V (p.Asp41Val), rs925840558, gnomAD 11-125625885-A-T, CADD 2.29
- D41E (p.Asp41Glu), rs749034825, gnomAD 11-125625886-C-A, CADD 8.69
- D41D (p.Asp41Asp), rs749034825, gnomAD 11-125625886-C-T, CADD 3.68
- M42T (p.Met42Thr), gnomAD rs1940677066
- M42V (p.Met42Val), gnomAD rs1458791146
- K43T (p.Lys43Thr), gnomAD 11-125627669-A-C, REVEL 0.06, CADD 20.80
- R44C (p.Arg44Cys), cosmic curated COSV54023, ExAC rs771939046, gnomAD rs771939046, REVEL 0.37, CADD 19.90
- R44H (p.Arg44His), rs537858020, 1000Genomes rs537858020, ExAC rs537858020, TOPMed rs537858020, REVEL 0.27, CADD 20.20, Variant assessed as somatic; moderate impact.
- R44P (p.Arg44Pro), 1000Genomes rs537858020, ExAC rs537858020, TOPMed rs537858020, gnomAD rs537858020, REVEL 0.38, CADD 19.80
- R44S (p.Arg44Ser), ExAC rs771939046, gnomAD rs771939046
- R44R (p.Arg44Arg), gnomAD 11-125625926-C-A, CADD 12.30
- R44* (p.Arg44Ter), rs1940573936, gnomAD 11-125625926-C-T, CADD 36.00
- R44G (p.Arg44Gly), gnomAD 11-125625926-C-G, CADD 22.60
- A45D (p.Ala45Asp), ExAC rs760734978, gnomAD rs760734978, REVEL 0.15, CADD 19.30
- A45S (p.Ala45Ser), TOPMed rs1565361807, REVEL 0.20, CADD 19.90
- A45V (p.Ala45Val), ExAC rs760734978, gnomAD rs760734978, Uncertain significance, not specified
- A45C (p.Ala45Cys), gnomAD 11-125625893-ACG-, CADD 25.00
- A45G (p.Ala45Gly), rs1452742433, gnomAD 11-125625900-C-G, CADD 17.30
- A45A (p.Ala45Ala), rs1940572431, gnomAD 11-125625901-T-C, CADD 9.33
- A45T (p.Ala45Thr), rs1453731906, gnomAD 11-125625917-G-A, CADD 0.91
- A45E (p.Ala45Glu), gnomAD 11-125625924-C-A, CADD 23.30
- V46A (p.Val46Ala), cosmic curated COSV54023, REVEL 0.06, CADD 19.30
- V46I (p.Val46Ile), cosmic curated COSV10512, ExAC rs768467449, TOPMed rs768467449, gnomAD rs768467449, REVEL 0.07, CADD 13.50
- V46L (p.Val46Leu), ExAC rs768467449, TOPMed rs768467449, gnomAD rs768467449, REVEL 0.07, CADD 13.00
- V46R (p.Val46Arg), rs1565361813, gnomAD 11-125627674-G-GC, CADD 19.00
- D47G (p.Asp47Gly), NCI-TCGA Cosmic COSV9962, cosmic curated COSV99629, REVEL 0.25, CADD 21.30, Variant assessed as somatic; moderate impact.
- C48* (p.Cys48Ter), gnomAD rs1367390698, CADD 16.50
- C48Y (p.Cys48Tyr), gnomAD 11-125625810-G-A, CADD 7.03
- C48C (p.Cys48Cys), rs1277851631, gnomAD 11-125625811-C-T, CADD 5.50
- C48G (p.Cys48Gly), gnomAD 11-125627683-T-G, REVEL 0.22, CADD 20.20
- P49S (p.Pro49Ser), TOPMed rs1940678451, gnomAD rs1940678451
- P49T (p.Pro49Thr), TOPMed rs1940678451, gnomAD rs1940678451, REVEL 0.08, CADD 19.30
- P49A (p.Pro49Ala), rs76045215, gnomAD 11-125625851-C-G, CADD 0.00
- P49H (p.Pro49His), rs1283851911, gnomAD 11-125625852-C-A, CADD 6.73
- P49P (p.Pro49Pro), rs890376583, gnomAD 11-125625853-C-T, CADD 1.86
- P49L (p.Pro49Leu), rs1424287019, gnomAD 11-125625948-C-T, CADD 13.20
- E50K (p.Glu50Lys), Ensembl rs2135972346, REVEL 0.25, CADD 20.60
- N51S (p.Asn51Ser), Ensembl rs1565361841, REVEL 0.12, CADD 21.30
- N51K (p.Asn51Lys), rs1565361845, gnomAD 11-125627693-ATAT, CADD 18.30
- I52T (p.Ile52Thr), cosmic curated COSV10879
- I52V (p.Ile52Val), gnomAD 11-125627695-A-G, REVEL 0.06, CADD 21.00
- I52S (p.Ile52Ser), gnomAD 11-125627696-T-G, REVEL 0.42, CADD 21.10
- K53K (p.Lys53Lys), rs372546907, gnomAD 11-125627700-G-A, CADD 18.10
- K54T (p.Lys54Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K54R (p.Lys54Arg), rs957835845, gnomAD 11-125627697-TAAG, CADD 18.30
Public CHEK1 analysis runs
- CHEK1 analysis run — CHEK1 (854 variants) — completed 2026-08-20