CCNE1 (G1/S-specific cyclin-E1) variants and mutations
CCNE1 (also known as G1/S-specific cyclin-E1) is a human protein-coding gene encoding a g1/S-specific cyclin-E1 protein. It activates CDK2 near the G1-to-S transition, promoting DNA-replication entry and centrosome duplication. Amplification or overexpression is common in high-grade serous ovarian cancer and several other tumors and can contribute to genomic instability and treatment resistance. This analysis covers 883 CCNE1 variants and mutations. Of these, 54% have computational variant effect predictions. Disease context includes neurodegenerative disease, Abnormality of the skeletal system, and urinary bladder cancer. Example CCNE1 variants include P2L, P2Q, and P2R.
Variant analysis overview
- Gene: CCNE1
- Protein: G1/S-specific cyclin-E1
- UniProt accession: P24864
- Organism: Homo sapiens
- Variants analyzed: 883
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 733 unspecified-consequence records; 77 missense variants; 54 synonymous variants; 4 frameshift variants; 5 stop-gained variants; 4 splice-region variants; 3 in-frame deletions; 3 substitution
- Prediction scores: 474 variants have prediction scores (54% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, Abnormality of the skeletal system, urinary bladder cancer, gastric carcinoma, urinary bladder carcinoma, esophageal adenocarcinoma, obesity disorder, colorectal adenocarcinoma, skin basal cell carcinoma, endometrial endometrioid adenocarcinoma, breast carcinoma, colorectal cancer.
Protein structure and variant hotspots
- Protein features: 5 post-translational modification sites.
- PTM context: 9 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 CCNE1 variants
Examples include P2L, P2Q, P2R, P2S, P2T, P2A, P2P, R3M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), Ensembl rs1599594280, REVEL 0.07, CADD 29.20
- P2Q (p.Pro2Gln), Ensembl rs1599594280, REVEL 0.04, CADD 24.70
- P2R (p.Pro2Arg), Ensembl rs1599594280, REVEL 0.07, CADD 26.80
- P2S (p.Pro2Ser), TOPMed rs995865961, gnomAD rs995865961, REVEL 0.12, CADD 23.90
- P2T (p.Pro2Thr), gnomAD 19-29812559-C-A, REVEL 0.07, CADD 25.20
- P2A (p.Pro2Ala), gnomAD 19-29812559-C-G, REVEL 0.07, CADD 25.10
- P2P (p.Pro2Pro), gnomAD 19-29812561-G-T, CADD 17.00
- R3M (p.Arg3Met), TOPMed rs1973915688, REVEL 0.07, CADD 23.60
- R3W (p.Arg3Trp), gnomAD 19-29812562-A-T, REVEL 0.14, CADD 25.30
- R3G (p.Arg3Gly), gnomAD 19-29812562-A-G, REVEL 0.10, CADD 23.70
- R3R (p.Arg3Arg), rs1344327143, gnomAD 19-29812564-G-A, CADD 15.30
- R3S (p.Arg3Ser), gnomAD 19-29812564-G-T, REVEL 0.05, CADD 22.90
- E4G (p.Glu4Gly), Ensembl rs2145714554, REVEL 0.07, CADD 27.40
- E4V (p.Glu4Val), Ensembl rs2145714554
- E4S (p.Glu4Ser), gnomAD 19-29812562-AG-A, CADD 27.10
- E4K (p.Glu4Lys), gnomAD 19-29812565-G-A, REVEL 0.05, CADD 23.40
- E4D (p.Glu4Asp), gnomAD 19-29812567-G-T, REVEL 0.03, CADD 19.90
- E4E (p.Glu4Glu), rs1973915822, gnomAD 19-29812567-G-A, CADD 13.20
- R5C (p.Arg5Cys), Ensembl rs2145714565, REVEL 0.16, CADD 25.10, Uncertain significance, not specified
- R5H (p.Arg5His), TOPMed rs1014086924, gnomAD rs1014086924, REVEL 0.06, CADD 24.80, Uncertain significance
- R5L (p.Arg5Leu), TOPMed rs1014086924, gnomAD rs1014086924, REVEL 0.05, CADD 24.90, Uncertain significance, not specified
- R5G (p.Arg5Gly), gnomAD 19-29812568-C-G, REVEL 0.07, CADD 26.70
- R5S (p.Arg5Ser), gnomAD 19-29812568-C-A, REVEL 0.06, CADD 22.20
- R5R (p.Arg5Arg), gnomAD 19-29812570-C-T, CADD 14.80
- R6G (p.Arg6Gly), Ensembl rs2145714574, REVEL 0.04, CADD 23.60
- R6M (p.Arg6Met), Ensembl rs2145714579, REVEL 0.06, CADD 22.40
- R6R (p.Arg6Arg), gnomAD 19-29812573-G-A, CADD 14.50
- E7G (p.Glu7Gly), Ensembl rs2145714587
- E7K (p.Glu7Lys), TOPMed rs1392000524, gnomAD rs1392000524, REVEL 0.06, CADD 23.60
- E7* (p.Glu7Ter), gnomAD 19-29812574-G-T, CADD 46.00
- E7D (p.Glu7Asp), gnomAD 19-29812576-G-T, REVEL 0.04, CADD 22.80
- R8P (p.Arg8Pro), gnomAD rs1284831314
- R8Q (p.Arg8Gln), gnomAD rs1284831314, REVEL 0.07, CADD 33.00
- R8W (p.Arg8Trp), 1000Genomes rs765558494, ExAC rs765558494, TOPMed rs765558494, gnomAD rs765558494, REVEL 0.16, CADD 29.10, Uncertain significance, not specified
- R8R (p.Arg8Arg), rs765558494, gnomAD 19-29812577-C-A, CADD 17.60
- R8L (p.Arg8Leu), gnomAD 19-29812578-G-T, REVEL 0.06, CADD 33.00
- D9H (p.Asp9His), ESP rs377233800, ExAC rs377233800, TOPMed rs377233800, gnomAD rs377233800, REVEL 0.09, CADD 32.00
- D9Y (p.Asp9Tyr), ESP rs377233800, ExAC rs377233800, TOPMed rs377233800, gnomAD rs377233800, REVEL 0.09, CADD 33.00
- D9N (p.Asp9Asn), gnomAD 19-29812690-G-A, REVEL 0.11, CADD 25.10
- D9V (p.Asp9Val), gnomAD 19-29812690-GA-G, CADD 32.00
- D9G (p.Asp9Gly), gnomAD 19-29812691-A-G, REVEL 0.06, CADD 24.70
- A10G (p.Ala10Gly), TOPMed rs1242761919, gnomAD rs1242761919
- A10V (p.Ala10Val), TOPMed rs1242761919, gnomAD rs1242761919, REVEL 0.04, CADD 22.50
- A10R (p.Ala10Arg), gnomAD 19-29812692-TG-T, CADD 32.00
- A10S (p.Ala10Ser), gnomAD 19-29812693-G-T, REVEL 0.04, CADD 22.60
- A10T (p.Ala10Thr), gnomAD 19-29812693-G-A, REVEL 0.04, CADD 23.30
- A10A (p.Ala10Ala), gnomAD 19-29812695-G-T, CADD 11.50
- p.Lys11 Asp14del, gnomAD 19-29812694-CGAAG, CADD 22.60
- K11M (p.Lys11Met), gnomAD 19-29812697-A-T, REVEL 0.03, CADD 23.00
- E12K (p.Glu12Lys), gnomAD rs1357182033, REVEL 0.08, CADD 24.20
- E12* (p.Glu12Ter), gnomAD 19-29812699-G-T, CADD 42.00
- E12D (p.Glu12Asp), gnomAD 19-29812701-G-T, REVEL 0.06, CADD 1.85
- E12E (p.Glu12Glu), rs1204581946, gnomAD 19-29812701-G-A, CADD 4.43
- R13G (p.Arg13Gly), gnomAD rs1282484032
- R13Q (p.Arg13Gln), TOPMed rs1244850159, gnomAD rs1244850159, REVEL 0.03, CADD 8.82
- R13W (p.Arg13Trp), gnomAD rs1282484032, REVEL 0.07, CADD 23.60, Uncertain significance, not specified
- R13R (p.Arg13Arg), rs1282484032, gnomAD 19-29812702-C-A, CADD 14.10
- R13L (p.Arg13Leu), gnomAD 19-29812703-G-T, REVEL 0.05, CADD 10.70
- D14E (p.Asp14Glu), ExAC rs763320381, TOPMed rs763320381, gnomAD rs763320381, REVEL 0.04, CADD 14.40
- D14H (p.Asp14His), TOPMed rs1973921189, gnomAD rs1973921189, REVEL 0.02, CADD 19.70
- D14N (p.Asp14Asn), gnomAD 19-29812705-G-A, REVEL 0.02, CADD 18.40
- D14D (p.Asp14Asp), rs763320381, gnomAD 19-29812707-C-T, CADD 13.10
- T15A (p.Thr15Ala), TOPMed rs1973921368, REVEL 0.04, CADD 13.70
- T15S (p.Thr15Ser), gnomAD 19-29812708-A-T, REVEL 0.01, CADD 12.50
- T15I (p.Thr15Ile), gnomAD 19-29812709-C-T, REVEL 0.02, CADD 14.00
- T15T (p.Thr15Thr), rs139551337, gnomAD 19-29812710-C-T, CADD 10.40
- M16R (p.Met16Arg), ExAC rs752180309, TOPMed rs752180309, gnomAD rs752180309
- M16T (p.Met16Thr), ExAC rs752180309, TOPMed rs752180309, gnomAD rs752180309
- M16V (p.Met16Val), TOPMed rs1973921541, gnomAD rs1973921541
- K17E (p.Lys17Glu), gnomAD 19-29812714-A-G, REVEL 0.04, CADD 22.90
- K17* (p.Lys17Ter), gnomAD 19-29812714-A-T, CADD 39.00
- K17T (p.Lys17Thr), gnomAD 19-29812715-A-C, REVEL 0.03, CADD 22.50
- K17K (p.Lys17Lys), rs767188260, gnomAD 19-29812716-G-A, CADD 10.90
- E18G (p.Glu18Gly), Ensembl rs2145715080
- E18K (p.Glu18Lys), cosmic curated COSV52904, TOPMed rs1305959499, gnomAD rs1305959499, REVEL 0.03, CADD 23.50
- E18Q (p.Glu18Gln), gnomAD 19-29812717-G-C, REVEL 0.04, CADD 23.20
- D19A (p.Asp19Ala), TOPMed rs1469198229, gnomAD rs1469198229, REVEL 0.06, CADD 23.40
- D19E (p.Asp19Glu), TOPMed rs908113662, gnomAD rs908113662, REVEL 0.04, CADD 4.88
- D19G (p.Asp19Gly), TOPMed rs1469198229, gnomAD rs1469198229
- D19H (p.Asp19His), ExAC rs749906913, TOPMed rs749906913, gnomAD rs749906913, REVEL 0.11, CADD 25.00
- D19V (p.Asp19Val), TOPMed rs1469198229, gnomAD rs1469198229, REVEL 0.06, CADD 23.40
- G20D (p.Gly20Asp), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99388, Ensembl rs2145715116, REVEL 0.06, CADD 20.20, Variant assessed as somatic; moderate impact.
- G20S (p.Gly20Ser), TOPMed rs1409795988, gnomAD rs1409795988, REVEL 0.03, CADD 16.30
- G20G (p.Gly20Gly), rs755757691, gnomAD 19-29812725-C-A, CADD 6.67
- G21S (p.Gly21Ser), TOPMed rs1275105376, gnomAD rs1275105376, REVEL 0.03, CADD 15.30
- G21V (p.Gly21Val), ExAC rs779694639, gnomAD rs779694639, REVEL 0.08, CADD 18.30
- G21C (p.Gly21Cys), gnomAD 19-29812726-G-T, REVEL 0.12, CADD 23.90
- G21D (p.Gly21Asp), gnomAD 19-29812727-G-A, REVEL 0.07, CADD 17.40
- G21G (p.Gly21Gly), gnomAD 19-29812728-C-A, CADD 11.60
- A22G (p.Ala22Gly), 1000Genomes rs578227778, TOPMed rs578227778, gnomAD rs578227778, REVEL 0.10, CADD 10.30
- A22P (p.Ala22Pro), NCI-TCGA Cosmic COSV5290, cosmic curated COSV52903, Variant assessed as somatic; moderate impact.
- A22T (p.Ala22Thr), rs749045990, NCI-TCGA Cosmic COSV5290, ExAC rs749045990, gnomAD rs749045990, REVEL 0.03, CADD 3.32, Variant assessed as somatic; moderate impact.
- A22V (p.Ala22Val), rs578227778, NCI-TCGA Cosmic COSV5290, cosmic curated COSV52903, 1000Genomes rs578227778, REVEL 0.08, CADD 6.55, Uncertain significance, not specified
- A22S (p.Ala22Ser), gnomAD 19-29812729-G-T, REVEL 0.02, CADD 1.81
- A22A (p.Ala22Ala), rs754856510, gnomAD 19-29812731-G-C, CADD 2.21
- E23D (p.Glu23Asp), gnomAD rs1973922731, REVEL 0.03, CADD 1.12
- E23G (p.Glu23Gly), cosmic curated COSV52905, Ensembl rs2145715161, REVEL 0.07, CADD 25.80
- F24L (p.Phe24Leu), ExAC rs778672861, gnomAD rs778672861, REVEL 0.01, CADD 14.00
- F24F (p.Phe24Phe), rs778672861, gnomAD 19-29812737-C-T, CADD 12.80
- S25L (p.Ser25Leu), cosmic curated COSV52903, ExAC rs771972554, TOPMed rs771972554, gnomAD rs771972554, REVEL 0.17, CADD 23.10
- S25T (p.Ser25Thr), gnomAD 19-29812738-T-A, REVEL 0.04, CADD 15.70
- S25* (p.Ser25Ter), gnomAD 19-29812739-C-A, CADD 38.00
- S25S (p.Ser25Ser), gnomAD 19-29812740-G-C, CADD 3.47
- A26S (p.Ala26Ser), TOPMed rs1250060364, gnomAD rs1250060364, REVEL 0.03, CADD 15.30
- A26T (p.Ala26Thr), TOPMed rs1250060364, gnomAD rs1250060364
- A26L (p.Ala26Leu), gnomAD 19-29812736-TCTCG, CADD 26.40
- A26G (p.Ala26Gly), gnomAD 19-29812742-C-G, REVEL 0.02, CADD 13.60
- A26V (p.Ala26Val), gnomAD 19-29812742-C-T, REVEL 0.03, CADD 8.72
- A26D (p.Ala26Asp), gnomAD 19-29812742-C-A, REVEL 0.01, CADD 13.00
- R27C (p.Arg27Cys), rs776712074, NCI-TCGA Cosmic COSV5290, cosmic curated COSV52904, ExAC rs776712074, REVEL 0.27, CADD 25.90, Variant assessed as somatic; moderate impact.
- R27G (p.Arg27Gly), ExAC rs776712074, gnomAD rs776712074, REVEL 0.23, CADD 27.10
- R27H (p.Arg27His), ExAC rs745919586, TOPMed rs745919586, gnomAD rs745919586, REVEL 0.19, CADD 25.80
- R27L (p.Arg27Leu), ExAC rs745919586, TOPMed rs745919586, gnomAD rs745919586
- R27S (p.Arg27Ser), gnomAD 19-29812744-C-A, REVEL 0.18, CADD 27.30
- R27P (p.Arg27Pro), gnomAD 19-29812745-G-C, REVEL 0.19, CADD 31.00
- R27R (p.Arg27Arg), rs1262666288, gnomAD 19-29812746-C-T, CADD 13.80
- S28F (p.Ser28Phe), ESP rs145289511, ExAC rs145289511
- S28Y (p.Ser28Tyr), gnomAD 19-29812748-C-A, REVEL 0.12, CADD 27.60
- S28C (p.Ser28Cys), gnomAD 19-29812748-C-G, REVEL 0.10, CADD 28.20
- S28S (p.Ser28Ser), rs1973923524, gnomAD 19-29812749-C-A, CADD 15.70
- R29G (p.Arg29Gly), 1000Genomes rs1973923599, TOPMed rs1973923599, REVEL 0.16, CADD 32.00
- R29T (p.Arg29Thr), Ensembl rs2145715226
- R29M (p.Arg29Met), gnomAD 19-29812751-G-T, REVEL 0.24, CADD 32.00
- R29K (p.Arg29Lys), gnomAD 19-29812751-G-A, REVEL 0.14, CADD 26.60
- R29S (p.Arg29Ser), gnomAD 19-29812752-G-T, REVEL 0.16, CADD 31.00
- R29R (p.Arg29Arg), rs775840112, gnomAD 19-29812752-G-A, CADD 15.70
- K30R (p.Lys30Arg), gnomAD rs1205916639, REVEL 0.23, CADD 32.00
- K30Q (p.Lys30Gln), gnomAD 19-29812753-A-C, REVEL 0.26, CADD 33.00
- K30* (p.Lys30Ter), gnomAD 19-29812753-A-T, CADD 52.00
- K30N (p.Lys30Asn), gnomAD 19-29812755-G-T, REVEL 0.15, CADD 27.30
- K30K (p.Lys30Lys), rs1257543223, gnomAD 19-29812755-G-A, CADD 14.60
- R31G (p.Arg31Gly), gnomAD rs1443126704, REVEL 0.32, CADD 34.00
- R31K (p.Arg31Lys), gnomAD 19-29812757-G-A, REVEL 0.23, CADD 28.10
- R31S (p.Arg31Ser), gnomAD 19-29812758-G-T, REVEL 0.20, CADD 32.00
- R31R (p.Arg31Arg), gnomAD 19-29812758-G-A, CADD 15.60
- K32R (p.Lys32Arg), gnomAD 19-29812760-A-G, REVEL 0.16, MetaLR 0.29
- K32M (p.Lys32Met), gnomAD 19-29812760-A-T, REVEL 0.33, MetaLR 0.35
- K32K (p.Lys32Lys), rs1973923958, gnomAD 19-29812761-G-A, CADD 13.60
- A33T (p.Ala33Thr), gnomAD rs1437724105, REVEL 0.13, CADD 32.00
- A33V (p.Ala33Val), gnomAD rs1186891855, REVEL 0.12, CADD 34.00
- A33E (p.Ala33Glu), gnomAD 19-29812763-C-A, REVEL 0.13, MetaLR 0.23
- N34K (p.Asn34Lys), ExAC rs763083338, gnomAD rs763083338, REVEL 0.08, CADD 24.10
- N34N (p.Asn34Asn), gnomAD 19-29812767-C-T, CADD 14.70
- V35M (p.Val35Met), ESP rs369751087, ExAC rs369751087, TOPMed rs369751087, gnomAD rs369751087, REVEL 0.23, CADD 32.00, Uncertain significance, not specified
- V35L (p.Val35Leu), gnomAD 19-29812768-G-T, REVEL 0.18, MetaLR 0.24
- V35G (p.Val35Gly), gnomAD 19-29812769-T-G, REVEL 0.22, MetaLR 0.25
- V35E (p.Val35Glu), gnomAD 19-29812769-T-A, REVEL 0.23, MetaLR 0.22
- V35V (p.Val35Val), gnomAD 19-29812770-G-T, CADD 15.40
- T36A (p.Thr36Ala), TOPMed rs1355673586, gnomAD rs1355673586, REVEL 0.14, CADD 21.90
- T36N (p.Thr36Asn), TOPMed rs1472595244, gnomAD rs1472595244, REVEL 0.07, CADD 23.40
- T36I (p.Thr36Ile), gnomAD 19-29812772-C-T, REVEL 0.05, MetaLR 0.06
- T36T (p.Thr36Thr), rs149152183, gnomAD 19-29812773-C-A, CADD 15.10
- V37I (p.Val37Ile), rs774836905, ExAC rs774836905, TOPMed rs774836905, gnomAD rs774836905, REVEL 0.06, CADD 21.80, Uncertain significance
- V37L (p.Val37Leu), rs774836905, ClinGen CA405261132, ClinVar RCV004152193, ExAC rs774836905, REVEL 0.05, CADD 24.70, Uncertain significance, not specified
- V37F (p.Val37Phe), gnomAD 19-29812774-G-T, REVEL 0.06, MetaLR 0.13
- V37V (p.Val37Val), gnomAD 19-29812776-T-A, CADD 15.70
- F38L (p.Phe38Leu), rs772724283, ClinGen CA9352140, ClinVar RCV004104704, ExAC rs772724283, REVEL 0.04, CADD 24.90, Uncertain significance, not specified
- L39F (p.Leu39Phe), Ensembl rs2145715735
- Q40* (p.Gln40Ter), Ensembl rs2145715739
- D41N (p.Asp41Asn), gnomAD rs1225643119, REVEL 0.15, CADD 33.00
- D41V (p.Asp41Val), TOPMed rs1280453007
- D41D (p.Asp41Asp), rs773909135, gnomAD 19-29812980-T-C, CADD 13.90
- P42L (p.Pro42Leu), ESP rs146376659, ExAC rs146376659, TOPMed rs146376659, gnomAD rs146376659, REVEL 0.08, CADD 23.20, Uncertain significance
- P42Q (p.Pro42Gln), rs146376659, ClinGen CA9352142, ClinVar RCV004194689, ESP rs146376659, REVEL 0.14, CADD 24.10, Uncertain significance, not specified
- P42P (p.Pro42Pro), gnomAD 19-29812983-A-T, CADD 10.70
- D43E (p.Asp43Glu), ExAC rs759252695, TOPMed rs759252695, gnomAD rs759252695, REVEL 0.07, CADD 27.00, Uncertain significance, not specified
- D43G (p.Asp43Gly), ExAC rs765951124, gnomAD rs765951124, REVEL 0.30, CADD 29.70
- D43H (p.Asp43His), Ensembl rs1973930374
- D43V (p.Asp43Val), ExAC rs765951124, gnomAD rs765951124, REVEL 0.37, CADD 32.00
- D43N (p.Asp43Asn), gnomAD 19-29812984-G-A, REVEL 0.17, MetaLR 0.31
- E44D (p.Glu44Asp), gnomAD rs1490679833, REVEL 0.11, CADD 23.40
- E44K (p.Glu44Lys), Ensembl rs1973930626, REVEL 0.18, CADD 33.00
- E44A (p.Glu44Ala), gnomAD 19-29812988-A-C, REVEL 0.17, MetaLR 0.24
- E44E (p.Glu44Glu), rs1490679833, gnomAD 19-29812989-A-G, CADD 14.80
- E45Q (p.Glu45Gln), gnomAD 19-29812990-G-C, REVEL 0.04, MetaLR 0.10
- M46I (p.Met46Ile), gnomAD rs1973930862, NCI-TCGA Cosmic COSV5290, cosmic curated COSV52904, REVEL 0.05, CADD 11.60, Variant assessed as somatic; moderate impact.
- M46T (p.Met46Thr), ExAC rs764828115, TOPMed rs764828115, gnomAD rs764828115, REVEL 0.07, CADD 22.80
- A47T (p.Ala47Thr), Ensembl rs2145715815
- A47V (p.Ala47Val), cosmic curated COSV10959, Ensembl rs2145715820
- A47G (p.Ala47Gly), gnomAD 19-29812997-C-G, REVEL 0.06, MetaLR 0.17
Public CCNE1 analysis runs
- CCNE1 analysis run — CCNE1 (883 variants) — completed 2026-08-19