CDK7 (Cyclin-dependent kinase 7) variants and mutations
CDK7 (also known as Cyclin-dependent kinase 7) is a human protein-coding gene encoding a cyclin-dependent kinase 7 protein. It activates other cell-cycle CDKs and also phosphorylates RNA polymerase II as part of TFIIH, linking cell-cycle control with transcription. Some cancers show strong dependence on CDK7-driven transcription, motivating development of selective inhibitors. This analysis covers 452 CDK7 variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes HIV infectious disease, neurodegenerative disease, and hypertensive disorder. Example CDK7 variants include A2T, A2S, and A2D.
Variant analysis overview
- Gene: CDK7
- Protein: Cyclin-dependent kinase 7
- UniProt accession: P50613
- Organism: Homo sapiens
- Variants analyzed: 452
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 296 unspecified-consequence records; 94 missense variants; 35 synonymous variants; 6 stop-gained variants; 13 frameshift variants; 4 splice-region variants; 3 stop lost; 1 substitution
- Prediction scores: 370 variants have prediction scores (82% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: HIV infectious disease, neurodegenerative disease, hypertensive disorder, B-cell chronic lymphocytic leukemia, cardiovascular disorder, autoimmune disorder of central nervous system, breast cancer, acute myeloid leukemia, non-small cell lung carcinoma, mantle cell lymphoma, hepatocellular carcinoma, breast carcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 18 binding sites; 5 post-translational modification sites.
- Structural context: 355 variants have structural context.
- PTM context: 12 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 CDK7 variants
Examples include A2T, A2S, A2D, A2V, A2A, L3V, L3L, L3Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), TOPMed rs1748849188, gnomAD rs1748849188, REVEL 0.09, CADD 24.50
- A2S (p.Ala2Ser), gnomAD 5-69234979-G-T, REVEL 0.09, CADD 23.90
- A2D (p.Ala2Asp), gnomAD 5-69234980-C-A, REVEL 0.20, CADD 23.80
- A2V (p.Ala2Val), gnomAD 5-69234980-C-T, REVEL 0.09, CADD 23.70
- A2A (p.Ala2Ala), rs1748849431, gnomAD 5-69234981-T-C, CADD 15.50
- L3V (p.Leu3Val), rs1219108385, ClinGen CA359913786, ClinVar RCV004145040, Likely benign, not specified
- L3L (p.Leu3Leu), rs1219108385, gnomAD 5-69234982-C-T, CADD 12.90
- L3Q (p.Leu3Gln), gnomAD 5-69234983-T-A, REVEL 0.06, CADD 23.10
- L3P (p.Leu3Pro), gnomAD 5-69234983-T-C, REVEL 0.11, CADD 23.10
- D4Y (p.Asp4Tyr), gnomAD 5-69234985-G-T, REVEL 0.27, CADD 27.80
- D4N (p.Asp4Asn), gnomAD 5-69234985-G-A, REVEL 0.05, CADD 23.90
- D4V (p.Asp4Val), gnomAD 5-69234986-A-T, REVEL 0.24, CADD 25.80
- D4D (p.Asp4Asp), rs1436190649, gnomAD 5-69234987-C-T, CADD 15.30
- D4E (p.Asp4Glu), gnomAD 5-69234987-C-A, REVEL 0.12, CADD 21.70
- V5M (p.Val5Met), 1000Genomes rs193107048, ExAC rs193107048, TOPMed rs193107048, gnomAD rs193107048, REVEL 0.14, CADD 23.20
- V5L (p.Val5Leu), gnomAD 5-69234988-G-T, REVEL 0.09, CADD 23.20
- V5A (p.Val5Ala), gnomAD 5-69234989-T-C, REVEL 0.10, CADD 21.80
- V5V (p.Val5Val), gnomAD 5-69234990-G-T, CADD 16.00
- K6T (p.Lys6Thr), gnomAD rs1196381635, REVEL 0.18, CADD 23.00
- K6E (p.Lys6Glu), gnomAD 5-69234991-A-G, REVEL 0.18, CADD 23.30
- K6R (p.Lys6Arg), gnomAD 5-69234992-A-G, REVEL 0.05, CADD 23.50
- K6K (p.Lys6Lys), gnomAD 5-69234993-G-A, CADD 15.70
- K6N (p.Lys6Asn), gnomAD 5-69234993-G-T, REVEL 0.07, CADD 23.40
- S7Y (p.Ser7Tyr), NCI-TCGA TCGA novel, REVEL 0.20, CADD 24.50, Variant assessed as somatic; moderate impact.
- S7A (p.Ser7Ala), gnomAD 5-69234994-T-G, REVEL 0.07, CADD 22.90
- S7F (p.Ser7Phe), gnomAD 5-69234995-C-T, REVEL 0.19, CADD 24.60
- S7S (p.Ser7Ser), gnomAD 5-69234996-T-A, CADD 16.20
- R8W (p.Arg8Trp), NCI-TCGA Cosmic COSV5650, cosmic curated COSV56508, REVEL 0.22, CADD 32.00, Variant assessed as somatic; moderate impact.
- R8R (p.Arg8Arg), rs1237171626, gnomAD 5-69234997-C-A, CADD 17.30
- R8Q (p.Arg8Gln), gnomAD 5-69234998-G-A, REVEL 0.11, CADD 24.00
- R8L (p.Arg8Leu), gnomAD 5-69234998-G-T, REVEL 0.20, CADD 24.00
- A9T (p.Ala9Thr), Ensembl rs867116521, REVEL 0.16, CADD 23.50
- A9S (p.Ala9Ser), gnomAD 5-69235000-G-T, REVEL 0.17, CADD 22.80
- A9V (p.Ala9Val), gnomAD 5-69235001-C-T, REVEL 0.12, CADD 25.40
- A9E (p.Ala9Glu), gnomAD 5-69235001-C-A, REVEL 0.16, CADD 22.90
- A9A (p.Ala9Ala), rs943322252, gnomAD 5-69235002-A-T, CADD 11.40
- K10R (p.Lys10Arg), gnomAD rs1180242079, REVEL 0.04, CADD 23.10
- K10E (p.Lys10Glu), gnomAD 5-69235003-A-G, REVEL 0.19, CADD 23.50
- K10N (p.Lys10Asn), gnomAD 5-69235005-G-T, REVEL 0.04, CADD 22.90
- R11H (p.Arg11His), 1000Genomes rs555422765, ExAC rs555422765, TOPMed rs555422765, gnomAD rs555422765, REVEL 0.30, CADD 32.00
- R11L (p.Arg11Leu), 1000Genomes rs555422765, ExAC rs555422765, TOPMed rs555422765, gnomAD rs555422765, REVEL 0.26, CADD 25.80, Uncertain significance, not specified
- R11S (p.Arg11Ser), TOPMed rs1748852140, REVEL 0.23, CADD 28.10, Uncertain significance, not specified
- R11C (p.Arg11Cys), gnomAD 5-69235006-C-T, REVEL 0.23, CADD 32.00
- Y12F (p.Tyr12Phe), gnomAD 5-69235010-A-T, REVEL 0.41, CADD 29.10
- Y12C (p.Tyr12Cys), gnomAD 5-69235010-A-G, REVEL 0.73, CADD 32.00
- Y12* (p.Tyr12Ter), gnomAD 5-69235011-T-G, CADD 36.00
- E13K (p.Glu13Lys), gnomAD 5-69235012-G-A, REVEL 0.22, CADD 23.50
- E13V (p.Glu13Val), gnomAD 5-69235013-A-T, REVEL 0.46, CADD 26.20
- E13D (p.Glu13Asp), gnomAD 5-69235014-G-T, REVEL 0.20, CADD 19.00
- K14E (p.Lys14Glu), gnomAD 5-69235015-A-G, REVEL 0.32, CADD 31.00
- K14N (p.Lys14Asn), gnomAD 5-69235017-G-T, REVEL 0.25, CADD 23.10
- L15M (p.Leu15Met), gnomAD 5-69235018-C-A, REVEL 0.15, CADD 23.90
- L15Q (p.Leu15Gln), gnomAD 5-69235019-T-A, REVEL 0.27, CADD 25.50
- L15L (p.Leu15Leu), gnomAD 5-69235020-G-T, CADD 15.30
- D16Y (p.Asp16Tyr), ESP rs368259373, ExAC rs368259373, TOPMed rs368259373, gnomAD rs368259373, REVEL 0.27, CADD 32.00
- D16H (p.Asp16His), gnomAD 5-69235021-G-C, REVEL 0.21, CADD 25.90
- D16N (p.Asp16Asn), gnomAD 5-69235021-G-A, REVEL 0.10, CADD 23.60
- D16D (p.Asp16Asp), rs1173024193, gnomAD 5-69235023-C-T, CADD 14.90
- D16E (p.Asp16Glu), gnomAD 5-69235023-C-A, REVEL 0.18, CADD 18.70
- F17F (p.Phe17Phe), gnomAD 5-69235026-C-T, CADD 16.00
- F17L (p.Phe17Leu), gnomAD 5-69235026-C-A, REVEL 0.30, CADD 22.30
- L18R (p.Leu18Arg), gnomAD rs1173394021, REVEL 0.53, CADD 25.40
- L18I (p.Leu18Ile), gnomAD 5-69235027-C-A, REVEL 0.18, CADD 24.20
- L18L (p.Leu18Leu), gnomAD 5-69235029-T-C, CADD 14.90
- G19R (p.Gly19Arg), gnomAD 5-69235030-G-A, REVEL 0.95, CADD 32.00
- G19V (p.Gly19Val), gnomAD 5-69235031-G-T, REVEL 0.93, CADD 31.00
- G19G (p.Gly19Gly), rs1290213542, gnomAD 5-69235032-G-T, CADD 15.60
- E20K (p.Glu20Lys), NCI-TCGA TCGA novel, REVEL 0.46, CADD 32.00, Variant assessed as somatic; moderate impact.
- E20R (p.Glu20Arg), rs1425977847, gnomAD 5-69235025-TC-T, CADD 27.30
- E20V (p.Glu20Val), gnomAD 5-69235034-A-T, REVEL 0.63, CADD 32.00
- E20G (p.Glu20Gly), gnomAD 5-69235034-A-G, REVEL 0.50, CADD 32.00
- E20E (p.Glu20Glu), rs2150174923, gnomAD 5-69235035-G-A, CADD 14.20
- G21D (p.Gly21Asp), gnomAD 5-69235034-AG-A, CADD 27.00
- G21R (p.Gly21Arg), gnomAD 5-69235036-G-A, REVEL 0.97, CADD 32.00
- G21* (p.Gly21Ter), gnomAD 5-69235036-G-T, CADD 38.00
- G21G (p.Gly21Gly), rs775019182, gnomAD 5-69235038-A-G, CADD 17.10
- Q22* (p.Gln22Ter), ExAC rs761944819, gnomAD rs761944819, CADD 44.00
- Q22K (p.Gln22Lys), gnomAD 5-69235039-C-A, REVEL 0.24, CADD 23.90
- Q22R (p.Gln22Arg), gnomAD 5-69235040-A-G, REVEL 0.36, CADD 26.40
- Q22H (p.Gln22His), gnomAD 5-69235041-G-T, REVEL 0.34, CADD 33.00
- Q22Q (p.Gln22Gln), gnomAD 5-69235041-G-A, CADD 25.10
- A24T (p.Ala24Thr), gnomAD 5-69235397-G-A, REVEL 0.40, CADD 31.00
- A24D (p.Ala24Asp), gnomAD 5-69235398-C-A, REVEL 0.46, CADD 27.10
- A24V (p.Ala24Val), gnomAD 5-69235398-C-T, REVEL 0.40, CADD 28.20
- A24A (p.Ala24Ala), rs1748895075, gnomAD 5-69235399-C-T, CADD 14.50
- T25A (p.Thr25Ala), ExAC rs762773235, TOPMed rs762773235, gnomAD rs762773235, REVEL 0.22, CADD 24.00
- T25N (p.Thr25Asn), gnomAD 5-69235401-C-A, REVEL 0.11, CADD 22.60
- T25T (p.Thr25Thr), gnomAD 5-69235402-C-T, CADD 13.80
- V26I (p.Val26Ile), gnomAD 5-69235403-G-A, REVEL 0.58, CADD 29.70
- Y27C (p.Tyr27Cys), rs1383409705, gnomAD rs1383409705, ClinGen CA359913959, ClinVar RCV004260108, REVEL 0.74, CADD 32.00, Uncertain significance, not specified
- Y27Q (p.Tyr27Gln), rs747863522, gnomAD 5-69235403-GTT-G, CADD 32.00
- Y27L (p.Tyr27Leu), gnomAD 5-69235403-G-GT, CADD 33.00
- Y27T (p.Tyr27Thr), gnomAD 5-69235403-GT-G, CADD 32.00
- Y27* (p.Tyr27Ter), gnomAD 5-69235408-C-A, CADD 37.00
- Y27Y (p.Tyr27Tyr), gnomAD 5-69235408-C-T, CADD 13.50
- K28E (p.Lys28Glu), gnomAD rs1331838828, REVEL 0.43, CADD 24.00
- K28R (p.Lys28Arg), NCI-TCGA Cosmic COSV9984, cosmic curated COSV99841, REVEL 0.30, CADD 24.10, Variant assessed as somatic; moderate impact.
- K28N (p.Lys28Asn), gnomAD 5-69235411-G-T, REVEL 0.51, CADD 29.60
- A29T (p.Ala29Thr), 1000Genomes rs751443015, ExAC rs751443015, gnomAD rs751443015, REVEL 0.52, CADD 32.00
- A29D (p.Ala29Asp), gnomAD 5-69235413-C-A, REVEL 0.69, CADD 29.50
- A29V (p.Ala29Val), gnomAD 5-69235413-C-T, REVEL 0.38, CADD 32.00
- A29A (p.Ala29Ala), gnomAD 5-69235414-C-T, CADD 17.60
- R30K (p.Arg30Lys), gnomAD rs1245007515, REVEL 0.05, CADD 22.60
- R30S (p.Arg30Ser), TOPMed rs1302332585, gnomAD rs1302332585, REVEL 0.25, CADD 23.30
- R30T (p.Arg30Thr), NCI-TCGA Cosmic COSV5651, cosmic curated COSV56514, Variant assessed as somatic; moderate impact.
- R30E (p.Arg30Glu), gnomAD 5-69235412-GC-G, CADD 33.00
- D31E (p.Asp31Glu), TOPMed rs1748897258
- D31V (p.Asp31Val), ExAC rs757246767, gnomAD rs757246767
- D31Y (p.Asp31Tyr), NCI-TCGA Cosmic COSV5651, cosmic curated COSV56511, Variant assessed as somatic; moderate impact.
- D31G (p.Asp31Gly), gnomAD 5-69235419-A-G, REVEL 0.72, CADD 33.00
- K32R (p.Lys32Arg), gnomAD 5-69235420-TA-T, CADD 32.00
- K32E (p.Lys32Glu), gnomAD 5-69235421-A-G, REVEL 0.25, CADD 22.60
- K32K (p.Lys32Lys), gnomAD 5-69235423-G-A, CADD 14.70
- N33K (p.Asn33Lys), 1000Genomes rs2972388, ESP rs2972388, ExAC rs2972388, TOPMed rs2972388, REVEL 0.08, CADD 15.60
- N33N (p.Asn33Asn), rs2972388, gnomAD 5-69235426-C-T, CADD 13.80
- T34I (p.Thr34Ile), ExAC rs752051389, TOPMed rs752051389, gnomAD rs752051389, REVEL 0.38, CADD 25.70
- T34N (p.Thr34Asn), ExAC rs752051389, TOPMed rs752051389, gnomAD rs752051389, REVEL 0.13, CADD 22.00
- T34S (p.Thr34Ser), ExAC rs752051389, TOPMed rs752051389, gnomAD rs752051389, REVEL 0.11, CADD 22.00
- T34A (p.Thr34Ala), gnomAD 5-69235427-A-G, REVEL 0.21, CADD 24.00
- T34T (p.Thr34Thr), rs995029949, gnomAD 5-69235429-C-T, CADD 16.20
- N35H (p.Asn35His), 1000Genomes rs551300728, ExAC rs551300728, TOPMed rs551300728, gnomAD rs551300728, REVEL 0.09, CADD 25.30, Uncertain significance
- N35S (p.Asn35Ser), TOPMed rs1333139616, REVEL 0.05, CADD 22.40
- N35Y (p.Asn35Tyr), 1000Genomes rs551300728, ExAC rs551300728, TOPMed rs551300728, gnomAD rs551300728, REVEL 0.20, CADD 25.80, Uncertain significance, not specified
- N35K (p.Asn35Lys), gnomAD 5-69235432-C-A, REVEL 0.05, CADD 22.30
- N35N (p.Asn35Asn), rs1488695111, gnomAD 5-69235432-C-T, CADD 12.60
- Q36E (p.Gln36Glu), Ensembl rs1561338969
- Q36R (p.Gln36Arg), ExAC rs779716833, TOPMed rs779716833, gnomAD rs779716833, REVEL 0.04, CADD 21.10
- Q36* (p.Gln36Ter), gnomAD 5-69235433-C-T, CADD 36.00
- Q36K (p.Gln36Lys), gnomAD 5-69235433-C-A, REVEL 0.07, CADD 18.50
- Q36Q (p.Gln36Gln), gnomAD 5-69235435-A-G, CADD 8.64
- Q36H (p.Gln36His), gnomAD 5-69235435-A-C, REVEL 0.13, CADD 17.20
- I37F (p.Ile37Phe), ExAC rs748896779, TOPMed rs748896779, gnomAD rs748896779, REVEL 0.34, CADD 23.40
- I37N (p.Ile37Asn), ExAC rs755309372, TOPMed rs755309372, gnomAD rs755309372
- I37T (p.Ile37Thr), ExAC rs755309372, TOPMed rs755309372, gnomAD rs755309372, REVEL 0.31, CADD 24.70
- I37V (p.Ile37Val), ExAC rs748896779, TOPMed rs748896779, gnomAD rs748896779, REVEL 0.15, CADD 22.70
- I37L (p.Ile37Leu), gnomAD 5-69235436-A-C, REVEL 0.24, CADD 23.20
- I37M (p.Ile37Met), gnomAD 5-69235438-T-G, REVEL 0.28, CADD 11.70
- V38V (p.Val38Val), rs779476831, gnomAD 5-69235441-C-A, CADD 15.90
- V38L (p.Val38Leu), rs1357947091, gnomAD 5-69250757-G-T, CADD 4.47
- V38M (p.Val38Met), rs1376592197, gnomAD 5-69250772-G-A, CADD 5.76
- V38G (p.Val38Gly), gnomAD 5-69250773-T-G, CADD 7.22
- A39V (p.Ala39Val), NCI-TCGA Cosmic COSV9984, cosmic curated COSV99841, Variant assessed as somatic; moderate impact.
- A39T (p.Ala39Thr), gnomAD 5-69235442-G-A, REVEL 0.83, CADD 32.00
- A39D (p.Ala39Asp), gnomAD 5-69235443-C-A, REVEL 0.88, CADD 28.50
- A39A (p.Ala39Ala), rs1748900706, gnomAD 5-69235444-C-T, CADD 16.20
- I40V (p.Ile40Val), TOPMed rs1748900918
- I40L (p.Ile40Leu), gnomAD 5-69235442-GC-G, CADD 33.00
- K41N (p.Lys41Asn), NCI-TCGA Cosmic COSV5651, cosmic curated COSV56512, Variant assessed as somatic; moderate impact.
- K41R (p.Lys41Arg), gnomAD 5-69235447-TA-T, CADD 32.00
- K42T (p.Lys42Thr), rs1376105619, gnomAD 5-69235451-A-AC, CADD 32.00
- K42N (p.Lys42Asn), gnomAD 5-69235453-A-C, REVEL 0.35, CADD 26.30
- I43L (p.Ile43Leu), cosmic curated COSV56513, Ensembl rs145665301
- I43T (p.Ile43Thr), gnomAD 5-69252419-T-C, REVEL 0.87, CADD 28.20
- I43I (p.Ile43Ile), gnomAD 5-69252420-C-A, CADD 13.70
- K44T (p.Lys44Thr), gnomAD 5-69252420-CAA-C, CADD 29.80
- K44E (p.Lys44Glu), gnomAD 5-69252421-A-G, REVEL 0.66, CADD 27.10
- K44R (p.Lys44Arg), gnomAD 5-69252422-A-G, REVEL 0.31, CADD 23.20
- K44K (p.Lys44Lys), gnomAD 5-69252423-A-G, CADD 10.90
- L45V (p.Leu45Val), ExAC rs758857281, TOPMed rs758857281, gnomAD rs758857281, REVEL 0.05, CADD 19.40
- L45F (p.Leu45Phe), gnomAD 5-69252424-C-T, REVEL 0.31, CADD 26.50
- L45I (p.Leu45Ile), gnomAD 5-69252424-C-A, REVEL 0.06, CADD 21.70
- L45P (p.Leu45Pro), gnomAD 5-69252425-T-C, REVEL 0.51, CADD 28.30
- L45R (p.Leu45Arg), gnomAD 5-69252425-T-G, REVEL 0.32, CADD 24.30
- L45L (p.Leu45Leu), gnomAD 5-69252426-T-G, CADD 11.90
- G46R (p.Gly46Arg), gnomAD 5-69252427-G-A, REVEL 0.48, CADD 34.00
- G46G (p.Gly46Gly), rs1406641331, gnomAD 5-69252429-A-G, CADD 14.20
- H47R (p.His47Arg), NCI-TCGA TCGA novel, REVEL 0.31, CADD 22.10, Variant assessed as somatic; moderate impact.
- H47Y (p.His47Tyr), NCI-TCGA Cosmic COSV9984, cosmic curated COSV99841, Variant assessed as somatic; moderate impact.
- H47H (p.His47His), gnomAD 5-69250789-T-C, CADD 7.93
- H47N (p.His47Asn), gnomAD 5-69252430-C-A, REVEL 0.17, CADD 21.50
- R48I (p.Arg48Ile), NCI-TCGA TCGA novel, REVEL 0.30, CADD 23.20, Variant assessed as somatic; moderate impact.
- R48T (p.Arg48Thr), ExAC rs778386185, gnomAD rs778386185, REVEL 0.44, CADD 26.20
- R48G (p.Arg48Gly), gnomAD 5-69252433-A-G, REVEL 0.42, CADD 26.80
- R48* (p.Arg48Ter), gnomAD 5-69252433-A-T, CADD 37.00
- R48R (p.Arg48Arg), gnomAD 5-69252435-A-G, CADD 13.30
- S49S (p.Ser49Ser), rs1441801418, gnomAD 5-69250750-T-G, CADD 6.15
- S49P (p.Ser49Pro), gnomAD 5-69252436-T-C, REVEL 0.20, CADD 23.20
- S49* (p.Ser49Ter), gnomAD 5-69252436-TC-T, CADD 34.00
- S49L (p.Ser49Leu), gnomAD 5-69252437-C-T, REVEL 0.19, CADD 24.30
- E50K (p.Glu50Lys), rs1178388461, gnomAD 5-69250745-G-A, CADD 5.05
Public CDK7 analysis runs
- CDK7 analysis run — CDK7 (452 variants) — completed 2026-08-20