CDK1 (Cyclin-dependent kinase 1) variants and mutations
CDK1 (also known as Cyclin-dependent kinase 1) is a human protein-coding gene encoding a cyclin-dependent kinase 1 protein. It is the central kinase that drives cells into mitosis and coordinates chromosome condensation, nuclear-envelope breakdown, spindle assembly, and other mitotic events. Because proliferating tumor cells depend on tightly regulated CDK1 activity, its pathway is extensively studied as an anticancer target. This analysis covers 377 CDK1 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes neurodegenerative disease, Alzheimer disease, and Parkinson disease. Example CDK1 variants include E2K, E2G, and E2E.
Variant analysis overview
- Gene: CDK1
- Protein: Cyclin-dependent kinase 1
- UniProt accession: P06493
- Organism: Homo sapiens
- Variants analyzed: 377
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 158 unspecified-consequence records; 111 missense variants; 76 synonymous variants; 13 frameshift variants; 8 stop-gained variants; 4 splice-region variants; 4 in-frame insertions; 1 protein altering variant; 1 in-frame deletions; 1 substitution
- Prediction scores: 312 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, Alzheimer disease, Parkinson disease, multiple sclerosis, lysosomal storage disease, prostatitis, B-cell chronic lymphocytic leukemia, autoimmune disorder of central nervous system, lagophthalmos, type 1 diabetes mellitus, portal hypertension, placental retention.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 15 post-translational modification sites.
- Structural context: 360 variants have structural context.
- PTM context: 30 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 CDK1 variants
Examples include E2K, E2G, E2E, E2D, D3H, D3G, D3D, D3E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2K (p.Glu2Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E2G (p.Glu2Gly), gnomAD 10-60780170-A-G, REVEL 0.15, CADD 28.40
- E2E (p.Glu2Glu), gnomAD 10-60780171-A-G, CADD 12.50
- E2D (p.Glu2Asp), gnomAD 10-60780171-A-T, REVEL 0.12, CADD 17.10
- D3H (p.Asp3His), gnomAD 10-60780172-G-C, REVEL 0.22, CADD 28.00
- D3G (p.Asp3Gly), gnomAD 10-60780173-A-G, REVEL 0.20, CADD 24.60
- D3D (p.Asp3Asp), rs1401482013, gnomAD 10-60780174-T-C, CADD 12.30
- D3E (p.Asp3Glu), gnomAD 10-60780174-T-G, REVEL 0.10, CADD 17.20
- Y4I (p.Tyr4Ile), gnomAD 10-60780173-AT-A, CADD 23.80
- Y4H (p.Tyr4His), gnomAD 10-60780175-T-C, REVEL 0.54, CADD 29.70
- Y4C (p.Tyr4Cys), gnomAD 10-60780176-A-G, REVEL 0.56, CADD 30.00
- Y4F (p.Tyr4Phe), gnomAD 10-60780176-A-T, REVEL 0.17, CADD 22.70
- Y4Y (p.Tyr4Tyr), gnomAD 10-60780177-T-C, CADD 11.50
- Y4* (p.Tyr4Ter), gnomAD 10-60780177-T-A, CADD 35.00
- T5I (p.Thr5Ile), TOPMed rs1002689539, gnomAD rs1002689539, REVEL 0.06, CADD 18.10
- T5N (p.Thr5Asn), TOPMed rs1002689539, gnomAD rs1002689539, REVEL 0.06, CADD 18.20
- T5A (p.Thr5Ala), gnomAD 10-60780178-A-G, REVEL 0.05, CADD 22.30
- T5T (p.Thr5Thr), rs2080259834, gnomAD 10-60780180-C-G, CADD 12.00
- K6E (p.Lys6Glu), gnomAD 10-60780181-A-G, REVEL 0.39, CADD 28.00
- K6R (p.Lys6Arg), gnomAD 10-60780182-A-G, REVEL 0.13, CADD 23.20
- K6N (p.Lys6Asn), gnomAD 10-60780183-A-T, REVEL 0.17, CADD 24.70
- K6K (p.Lys6Lys), gnomAD 10-60780183-A-G, CADD 11.90
- I7L (p.Ile7Leu), Ensembl rs1035478197
- I7T (p.Ile7Thr), TOPMed rs1468681761, REVEL 0.23, CADD 25.20
- I7* (p.Ile7Ter), gnomAD 10-60780180-CA-C, CADD 28.90
- I7N (p.Ile7Asn), gnomAD 10-60780180-C-CA, CADD 31.00
- I7V (p.Ile7Val), gnomAD 10-60780184-A-G, REVEL 0.16, CADD 22.20
- I7M (p.Ile7Met), gnomAD 10-60780186-A-G, REVEL 0.11, CADD 23.40
- E8D (p.Glu8Asp), cosmic curated COSV10734, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E8Q (p.Glu8Gln), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- E8* (p.Glu8Ter), gnomAD 10-60780187-G-T, CADD 43.00
- E8G (p.Glu8Gly), gnomAD 10-60780188-A-G, REVEL 0.36, CADD 32.00
- E8E (p.Glu8Glu), gnomAD 10-60780189-G-A, CADD 13.50
- K9R (p.Lys9Arg), NCI-TCGA Cosmic COSV5735, cosmic curated COSV57350, REVEL 0.32, CADD 29.80, Variant assessed as somatic; moderate impact.
- K9E (p.Lys9Glu), gnomAD 10-60780190-A-G, REVEL 0.56, CADD 31.00
- K9K (p.Lys9Lys), gnomAD 10-60780192-A-G, CADD 14.30
- I10M (p.Ile10Met), gnomAD rs1179034229, REVEL 0.40, CADD 25.90
- I10T (p.Ile10Thr), ExAC rs745479111, gnomAD rs745479111, REVEL 0.51, CADD 25.10
- I10L (p.Ile10Leu), gnomAD 10-60780189-GA-G, CADD 32.00
- I10V (p.Ile10Val), gnomAD 10-60780193-A-G, REVEL 0.17, CADD 22.70
- I10I (p.Ile10Ile), gnomAD 10-60780195-T-A, CADD 15.50
- G11R (p.Gly11Arg), gnomAD 10-60780196-G-A, REVEL 0.88, CADD 33.00
- G11* (p.Gly11Ter), gnomAD 10-60780196-G-T, CADD 43.00
- G11E (p.Gly11Glu), gnomAD 10-60780197-G-A, REVEL 0.89, CADD 31.00
- G11V (p.Gly11Val), gnomAD 10-60780197-G-T, REVEL 0.87, CADD 33.00
- G11G (p.Gly11Gly), gnomAD 10-60780198-A-G, CADD 17.30
- E12K (p.Glu12Lys), gnomAD 10-60780199-G-A, REVEL 0.49, CADD 32.00
- E12G (p.Glu12Gly), gnomAD 10-60780200-A-G, REVEL 0.72, CADD 33.00
- E12D (p.Glu12Asp), gnomAD 10-60780201-A-T, REVEL 0.45, CADD 27.90
- E12E (p.Glu12Glu), gnomAD 10-60780201-A-G, CADD 22.10
- G13R (p.Gly13Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G13C (p.Gly13Cys), gnomAD 10-60780202-G-T, REVEL 0.96, CADD 36.00
- G13S (p.Gly13Ser), gnomAD 10-60780202-G-A, REVEL 0.97, CADD 36.00
- T14S (p.Thr14Ser), TOPMed rs1201393937, gnomAD rs1201393937, REVEL 0.36, CADD 25.50
- T14T (p.Thr14Thr), gnomAD 10-60784709-C-T, CADD 12.60
- Y15* (p.Tyr15Ter), TOPMed rs1403343549, gnomAD rs1403343549, CADD 36.00
- Y15H (p.Tyr15His), gnomAD 10-60784710-T-C, REVEL 0.55, CADD 29.10
- Y15F (p.Tyr15Phe), gnomAD 10-60784711-A-T, REVEL 0.38, CADD 26.80
- Y15Y (p.Tyr15Tyr), gnomAD 10-60784712-T-C, CADD 9.99
- G16A (p.Gly16Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V17D (p.Val17Asp), gnomAD 10-60784717-T-A, REVEL 0.57, CADD 29.20
- V18L (p.Val18Leu), NCI-TCGA Cosmic COSV5735, cosmic curated COSV57350, Variant assessed as somatic; moderate impact.
- V18V (p.Val18Val), rs2080301039, gnomAD 10-60784721-G-T, CADD 8.05
- Y19C (p.Tyr19Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K20* (p.Lys20Ter), gnomAD 10-60784725-A-T, CADD 38.00
- K20K (p.Lys20Lys), gnomAD 10-60784727-G-A, CADD 8.14
- G21A (p.Gly21Ala), TOPMed rs1335188877, gnomAD rs1335188877, REVEL 0.29, CADD 20.60
- R22S (p.Arg22Ser), gnomAD 10-60784733-A-T, REVEL 0.27, CADD 23.40
- H23Q (p.His23Gln), TOPMed rs2080301172, gnomAD rs2080301172, REVEL 0.32, CADD 21.70
- H23R (p.His23Arg), ExAC rs111992007, REVEL 0.42, CADD 23.80
- H23H (p.His23His), gnomAD 10-60784736-C-T, CADD 9.25
- T25P (p.Thr25Pro), ExAC rs745660582, gnomAD rs745660582, REVEL 0.27, CADD 19.80
- G27D (p.Gly27Asp), gnomAD 10-60784747-G-A, REVEL 0.39, CADD 24.40
- Q28R (p.Gln28Arg), ESP rs377117179, TOPMed rs377117179, gnomAD rs377117179, REVEL 0.27, CADD 21.10, Uncertain significance, not specified
- Q28E (p.Gln28Glu), gnomAD 10-60784749-C-G, REVEL 0.19, CADD 17.10
- Q28Q (p.Gln28Gln), rs1411857391, gnomAD 10-60784751-A-G, CADD 11.00
- V29L (p.Val29Leu), Ensembl rs754755265, REVEL 0.09, CADD 16.30
- V29M (p.Val29Met), Ensembl rs754755265, REVEL 0.10, CADD 18.30
- V30L (p.Val30Leu), ExAC rs771969255, gnomAD rs771969255, REVEL 0.54, CADD 27.20
- V30V (p.Val30Val), rs774991794, gnomAD 10-60784757-A-G, CADD 9.96
- M32L (p.Met32Leu), gnomAD 10-60784761-A-C, REVEL 0.26, CADD 18.90
- K33K (p.Lys33Lys), rs2080301456, gnomAD 10-60784766-A-G, CADD 12.20
- K34K (p.Lys34Lys), gnomAD 10-60784769-A-G, CADD 12.80
- I35F (p.Ile35Phe), Ensembl rs2080301489
- R36I (p.Arg36Ile), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- R36K (p.Arg36Lys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, Variant assessed as somatic; moderate impact.
- E38A (p.Glu38Ala), gnomAD 10-60784780-A-C, REVEL 0.40, CADD 25.60
- S39N (p.Ser39Asn), cosmic curated COSV10814, TOPMed rs1370963471, REVEL 0.09, CADD 22.20
- S39G (p.Ser39Gly), gnomAD 10-60784782-A-G, REVEL 0.28, CADD 22.90
- E40K (p.Glu40Lys), ExAC rs746720738, gnomAD rs746720738, REVEL 0.43, CADD 29.80
- E40E (p.Glu40Glu), rs1420314266, gnomAD 10-60784787-A-G, CADD 12.90
- E40D (p.Glu40Asp), gnomAD 10-60784787-A-T, REVEL 0.11, CADD 21.40
- E41G (p.Glu41Gly), gnomAD 10-60784789-A-G, REVEL 0.31, CADD 31.00
- p.Glu42 Gly43insPro, gnomAD 10-60784793-A-ACC, CADD 21.60
- G43P (p.Gly43Pro), gnomAD 10-60784793-A-ACC, CADD 32.00
- G43F (p.Gly43Phe), gnomAD 10-60784793-AGGGG, CADD 32.00
- G43S (p.Gly43Ser), gnomAD 10-60784793-AGGGG, CADD 32.00
- G43V (p.Gly43Val), gnomAD 10-60784794-GGGGT, CADD 32.00
- p.Gly43delinsAlaArg, gnomAD 10-60784794-G-GCC, CADD 32.00
- G43A (p.Gly43Ala), gnomAD 10-60784795-G-C, REVEL 0.54, CADD 27.50
- G43G (p.Gly43Gly), gnomAD 10-60784796-G-C, CADD 10.10
- V44I (p.Val44Ile), gnomAD rs1297673130, REVEL 0.21, CADD 22.50
- V44del (p.Val44del), gnomAD 10-60784795-GGGT-, CADD 20.80
- V44F (p.Val44Phe), gnomAD 10-60784797-G-T, REVEL 0.46, CADD 27.80
- V44L (p.Val44Leu), gnomAD 10-60784797-G-C, REVEL 0.40, CADD 26.00
- V44A (p.Val44Ala), gnomAD 10-60784798-T-C, REVEL 0.47, CADD 28.20
- V44G (p.Val44Gly), gnomAD 10-60784798-T-G, REVEL 0.64, CADD 29.50
- V44V (p.Val44Val), gnomAD 10-60784799-T-C, CADD 11.60
- P45S (p.Pro45Ser), gnomAD 10-60784800-C-T, REVEL 0.42, CADD 26.20
- P45A (p.Pro45Ala), gnomAD 10-60784800-C-G, REVEL 0.43, CADD 25.40
- T47S (p.Thr47Ser), ExAC rs768015814, gnomAD rs768015814, REVEL 0.51, CADD 26.00
- A48T (p.Ala48Thr), gnomAD rs1454245611, REVEL 0.40, CADD 25.10
- I49V (p.Ile49Val), ESP rs142650572, ExAC rs142650572, TOPMed rs142650572, gnomAD rs142650572, REVEL 0.05, CADD 21.90
- I49I (p.Ile49Ile), gnomAD 10-60784814-T-C, CADD 12.90
- R50W (p.Arg50Trp), rs1312102931, NCI-TCGA Cosmic COSV5734, cosmic curated COSV57349, TOPMed rs1312102931, REVEL 0.46, CADD 31.00, Variant assessed as somatic; moderate impact.
- R50R (p.Arg50Arg), gnomAD 10-60784817-G-A, CADD 11.10
- I52V (p.Ile52Val), TOPMed rs1323937308, gnomAD rs1323937308, REVEL 0.11, CADD 22.10
- S53T (p.Ser53Thr), Ensembl rs2080301904
- L54L (p.Leu54Leu), rs1330355230, gnomAD 10-60784829-A-C, CADD 9.82
- E57Q (p.Glu57Gln), gnomAD rs1230964680, REVEL 0.44, CADD 27.90
- E57V (p.Glu57Val), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, Variant assessed as somatic; moderate impact.
- L58F (p.Leu58Phe), TOPMed rs1173075218, gnomAD rs1173075218
- L58I (p.Leu58Ile), TOPMed rs1173075218, gnomAD rs1173075218, REVEL 0.50, CADD 25.60
- L58L (p.Leu58Leu), rs762256498, gnomAD 10-60784841-T-G, CADD 9.19
- R59C (p.Arg59Cys), cosmic curated COSV10035, ESP rs8755, ExAC rs8755, TOPMed rs8755, REVEL 0.21, CADD 32.00
- R59G (p.Arg59Gly), ESP rs8755, ExAC rs8755, TOPMed rs8755, gnomAD rs8755
- R59H (p.Arg59His), cosmic curated COSV57348, ExAC rs773501650, gnomAD rs773501650, REVEL 0.06, CADD 23.20
- R59R (p.Arg59Arg), gnomAD 10-60784844-T-C, CADD 12.00
- P61S (p.Pro61Ser), rs1238716954, NCI-TCGA Cosmic COSV5734, cosmic curated COSV57349, TOPMed rs1238716954, REVEL 0.40, CADD 23.80, Variant assessed as somatic; moderate impact.
- N62N (p.Asn62Asn), rs911748890, gnomAD 10-60784853-T-C, CADD 11.20
- I63M (p.Ile63Met), gnomAD 10-60784856-A-G, REVEL 0.55, CADD 24.50
- V64I (p.Val64Ile), gnomAD 10-60784857-G-A, REVEL 0.34, CADD 26.40
- V64V (p.Val64Val), gnomAD 10-60784859-C-A, CADD 15.60
- S65R (p.Ser65Arg), gnomAD 10-60784860-A-C, REVEL 0.12, CADD 22.80
- p.Ser65 Leu66insPhePhe, rs1262575725, gnomAD 10-60785663-G-GTT, CADD 19.60
- L66F (p.Leu66Phe), cosmic curated COSV10035, gnomAD rs1460089100, REVEL 0.65, CADD 31.00
- L66I (p.Leu66Ile), gnomAD 10-60785665-C-A, REVEL 0.53, CADD 32.00
- L66P (p.Leu66Pro), gnomAD 10-60785666-T-C, REVEL 0.89, CADD 29.00
- L66L (p.Leu66Leu), gnomAD 10-60785667-T-C, CADD 8.98
- Q67K (p.Gln67Lys), gnomAD 10-60785668-C-A, REVEL 0.19, CADD 22.40
- Q67R (p.Gln67Arg), gnomAD 10-60785669-A-G, REVEL 0.20, CADD 22.40
- Q67L (p.Gln67Leu), gnomAD 10-60785669-A-T, REVEL 0.24, CADD 20.80
- Q67Q (p.Gln67Gln), gnomAD 10-60785670-G-A, CADD 6.35
- D68E (p.Asp68Glu), ExAC rs768316764, gnomAD rs768316764, REVEL 0.10, CADD 22.70
- D68Y (p.Asp68Tyr), gnomAD 10-60785671-G-T, REVEL 0.54, CADD 32.00
- V69M (p.Val69Met), gnomAD rs985951399, REVEL 0.56, CADD 29.20
- V69V (p.Val69Val), gnomAD 10-60785676-G-T, CADD 10.40
- L70F (p.Leu70Phe), ExAC rs780626115, gnomAD rs780626115, REVEL 0.47, AlphaMissense 0.46
- L70V (p.Leu70Val), rs780626115, ClinGen CA377067623, ClinVar RCV004110770, AlphaMissense 0.46, MetaLR 0.10, Uncertain significance, not specified
- L70I (p.Leu70Ile), gnomAD 10-60785677-C-A, REVEL 0.29, CADD 21.10
- L70H (p.Leu70His), gnomAD 10-60785678-T-A, REVEL 0.55, CADD 29.70
- L70L (p.Leu70Leu), gnomAD 10-60785679-T-C, CADD 10.30
- M71I (p.Met71Ile), gnomAD 10-60785682-G-T, REVEL 0.33, CADD 23.40
- Q72* (p.Gln72Ter), rs11540347, Ensembl rs11540347, CADD 39.00, Variant assessed as somatic; high impact.
- Q72K (p.Gln72Lys), gnomAD 10-60785683-C-A, REVEL 0.17, CADD 22.40
- Q72E (p.Gln72Glu), gnomAD 10-60785683-C-G, REVEL 0.18, CADD 19.10
- Q72P (p.Gln72Pro), gnomAD 10-60785684-A-C, REVEL 0.45, CADD 24.60
- Q72R (p.Gln72Arg), gnomAD 10-60785684-A-G, REVEL 0.30, CADD 22.70
- D73E (p.Asp73Glu), ExAC rs747663798, gnomAD rs747663798
- D73H (p.Asp73His), NCI-TCGA Cosmic COSV5735, cosmic curated COSV57350, Variant assessed as somatic; moderate impact.
- D73D (p.Asp73Asp), rs747663798, gnomAD 10-60785688-T-C, CADD 9.10
- S74Y (p.Ser74Tyr), gnomAD 10-60785690-C-A, REVEL 0.30, CADD 25.00
- R75G (p.Arg75Gly), gnomAD 10-60785692-A-G, REVEL 0.47, CADD 24.50
- L76L (p.Leu76Leu), gnomAD 10-60785695-T-C, CADD 10.30
- Y77C (p.Tyr77Cys), gnomAD 10-60785699-A-G, REVEL 0.70, CADD 27.60
- L78L (p.Leu78Leu), rs1243923852, gnomAD 10-60785703-C-T, CADD 11.40
- I79V (p.Ile79Val), gnomAD 10-60785704-A-G, REVEL 0.12, CADD 17.80
- F82L (p.Phe82Leu), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10035, Variant assessed as somatic; moderate impact.
- L83F (p.Leu83Phe), gnomAD 10-60785716-C-T, REVEL 0.46, CADD 26.10
- M85T (p.Met85Thr), NCI-TCGA Cosmic COSV5735, cosmic curated COSV57350, Variant assessed as somatic; moderate impact.
- K89K (p.Lys89Lys), rs1425708123, gnomAD 10-60785736-A-G, CADD 10.30
- Y90Y (p.Tyr90Tyr), rs144445383, gnomAD 10-60785739-C-T, CADD 9.00
- L91L (p.Leu91Leu), rs147689519, gnomAD 10-60785740-T-C, CADD 11.20
- D92Y (p.Asp92Tyr), Ensembl rs1589111889
- S93S (p.Ser93Ser), rs770857106, gnomAD 10-60785748-T-C, CADD 13.10
- I94I (p.Ile94Ile), gnomAD 10-60785751-C-T, CADD 8.11
- P95H (p.Pro95His), gnomAD 10-60785753-C-A, REVEL 0.32, CADD 26.10
- P96H (p.Pro96His), gnomAD 10-60785756-C-A, REVEL 0.06, CADD 23.10
- G97C (p.Gly97Cys), gnomAD 10-60785758-G-T, REVEL 0.24, CADD 25.20
- Q98H (p.Gln98His), ExAC rs771169549, gnomAD rs771169549, REVEL 0.13, CADD 22.30
Public CDK1 analysis runs
- CDK1 analysis run — CDK1 (377 variants) — completed 2026-08-20