CDK9 (Cyclin-dependent kinase 9) variants and mutations
CDK9 (also known as Cyclin-dependent kinase 9) is a human protein-coding gene encoding a cyclin-dependent kinase 9 protein. It promotes productive transcriptional elongation by phosphorylating RNA polymerase II and negative elongation factors as part of P-TEFb. Rapidly proliferating cancers can depend on this activity to maintain short-lived survival transcripts, making CDK9 a therapeutic target. This analysis covers 581 CDK9 variants and mutations. Of these, 93% have computational variant effect predictions. Disease context includes HIV infectious disease, Global developmental delay, and Intellectual disability. Example CDK9 variants include A2E, A2T, and A2S.
Variant analysis overview
- Gene: CDK9
- Protein: Cyclin-dependent kinase 9
- UniProt accession: P50750
- Organism: Homo sapiens
- Variants analyzed: 581
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 351 unspecified-consequence records; 139 missense variants; 9 stop-gained variants; 30 synonymous variants; 30 frameshift variants; 9 in-frame deletions; 8 in-frame insertions; 5 substitution
- Prediction scores: 543 variants have prediction scores (93% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: HIV infectious disease, Global developmental delay, Intellectual disability, choanal atresia, Abnormality of the ear, Developmental cataract, coloboma of iris, Seizure, Abnormal vertebral morphology, Preauricular skin tag, Abnormal heart morphology, Abnormality of vision.
Protein structure and variant hotspots
- Protein features: 1 domains; 4 binding sites; 13 post-translational modification sites.
- Structural context: 460 variants have structural context.
- PTM context: 14 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable CDK9 variants
Examples include A2E, A2T, A2S, A2V, A2G, A2A, A2D, A2P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2E (p.Ala2Glu), ExAC rs758230646, gnomAD rs758230646, REVEL 0.16, CADD 22.80
- A2T (p.Ala2Thr), TOPMed rs1290827114, gnomAD rs1290827114, REVEL 0.10, CADD 23.00
- A2S (p.Ala2Ser), rs1463583471, gnomAD 9-127785810-G-T, CADD 18.20, SIFT 0.01
- A2V (p.Ala2Val), gnomAD 9-127785811-C-T, CADD 16.10, SIFT 0.00
- A2G (p.Ala2Gly), gnomAD 9-127785811-C-G, CADD 15.80, SIFT 0.51
- A2A (p.Ala2Ala), gnomAD 9-127785812-G-A, CADD 15.60
- A2D (p.Ala2Asp), gnomAD 9-127785815-ACCCC, CADD 18.80
- A2P (p.Ala2Pro), gnomAD 9-127785822-G-C, CADD 17.90, SIFT 0.00
- p.Ala11 Pro12insGln, gnomAD 9-127785830-T-TCA, CADD 17.60
- K3E (p.Lys3Glu), NCI-TCGA TCGA novel, MetaLR 0.33, MetaSVM -0.37, Variant assessed as somatic; moderate impact.
- Q4E (p.Gln4Glu), TOPMed rs1239571832, MetaLR 0.20, MetaSVM -0.78
- Q4K (p.Gln4Lys), gnomAD 9-127785801-C-A, CADD 17.90, SIFT 0.00
- Q4* (p.Gln4Ter), gnomAD 9-127785801-C-T, CADD 18.30
- Q4P (p.Gln4Pro), gnomAD 9-127785802-A-C, CADD 18.90, SIFT 0.00
- Q4L (p.Gln4Leu), gnomAD 9-127785802-A-T, CADD 18.70, SIFT 0.00
- Q4R (p.Gln4Arg), gnomAD 9-127785802-A-G, CADD 19.10, SIFT 0.00
- Q4Q (p.Gln4Gln), rs1588536455, gnomAD 9-127785803-G-A, CADD 19.20
- Q4H (p.Gln4His), gnomAD 9-127785803-G-T, CADD 18.80, SIFT 0.00
- Y5* (p.Tyr5Ter), ExAC rs777792275, gnomAD rs777792275, CADD 36.00
- Y5C (p.Tyr5Cys), TOPMed rs1829309045, MetaLR 0.27, MetaSVM -0.57
- Y5H (p.Tyr5His), gnomAD rs1231461003, REVEL 0.31, CADD 23.60
- D6T (p.Asp6Thr), gnomAD 9-127785804-CG-C, CADD 17.30
- D6Y (p.Asp6Tyr), gnomAD 9-127785807-G-T, CADD 18.80, SIFT 0.00
- D6N (p.Asp6Asn), rs953375706, gnomAD 9-127785807-G-A, CADD 19.20, SIFT 0.00
- D6G (p.Asp6Gly), gnomAD 9-127785808-A-G, CADD 19.70, SIFT 0.00
- D6E (p.Asp6Glu), rs1588536473, gnomAD 9-127785809-C-A, CADD 18.30, SIFT 0.00
- D6D (p.Asp6Asp), gnomAD 9-127785809-C-T, CADD 18.80
- S7L (p.Ser7Leu), ExAC rs746864836, gnomAD rs746864836, REVEL 0.02, CADD 20.20
- V8M (p.Val8Met), Ensembl rs1829309358, REVEL 0.26, CADD 21.30
- E9A (p.Glu9Ala), gnomAD rs566144307, REVEL 0.29, CADD 21.50, Uncertain significance, not specified
- E9D (p.Glu9Asp), Ensembl rs1829309568, MetaLR 0.10, MetaSVM -0.95
- E9G (p.Glu9Gly), gnomAD rs566144307, REVEL 0.30, CADD 22.90, Uncertain significance
- C10G (p.Cys10Gly), gnomAD rs1251086320, MetaLR 0.20, MetaSVM -0.95
- C10S (p.Cys10Ser), gnomAD rs1829309695, REVEL 0.07, CADD 22.80
- P11H (p.Pro11His), TOPMed rs1456763070, gnomAD rs1456763070, REVEL 0.37, CADD 24.50
- P11L (p.Pro11Leu), TOPMed rs1456763070, gnomAD rs1456763070, MetaLR 0.28, MetaSVM -0.58
- P11S (p.Pro11Ser), rs1176651179, gnomAD 9-127785813-C-T, CADD 18.30, SIFT 0.00
- P11T (p.Pro11Thr), gnomAD 9-127785813-C-A, CADD 17.80, SIFT 0.00
- P11Q (p.Pro11Gln), gnomAD 9-127785814-C-A, CADD 17.60, SIFT 0.00
- P11R (p.Pro11Arg), gnomAD 9-127785814-C-G, CADD 17.70, SIFT 0.00
- P11P (p.Pro11Pro), gnomAD 9-127785815-A-G, CADD 16.20
- P11A (p.Pro11Ala), gnomAD 9-127785816-C-G, CADD 16.80, SIFT 0.00
- P11D (p.Pro11Asp), gnomAD 9-127785847-CCG-C, CADD 19.90
- P20del (p.Pro20del), gnomAD 9-127785849-GCGC-, CADD 19.40
- C13V (p.Cys13Val), NCI-TCGA TCGA novel, MetaLR 0.10, MetaSVM -0.96, Variant assessed as somatic; high impact.
- D14A (p.Asp14Ala), Ensembl rs1829309915, MetaLR 0.08, MetaSVM -1.06
- V16I (p.Val16Ile), TOPMed rs1829309971, REVEL 0.05, CADD 22.20
- S17C (p.Ser17Cys), ExAC rs781197980, TOPMed rs781197980, gnomAD rs781197980, REVEL 0.11, CADD 22.90
- S17F (p.Ser17Phe), ExAC rs781197980, TOPMed rs781197980, gnomAD rs781197980, REVEL 0.10, CADD 24.30
- S17G (p.Ser17Gly), rs1829294215, gnomAD 9-127785873-A-G, CADD 13.00, SIFT 0.55
- S17R (p.Ser17Arg), gnomAD 9-127785873-A-C, CADD 12.70, SIFT 0.01
- S17T (p.Ser17Thr), rs1041346574, gnomAD 9-127785874-G-C, CADD 15.30, SIFT 0.02
- S17I (p.Ser17Ile), rs1041346574, gnomAD 9-127785874-G-T, CADD 15.20, SIFT 0.01
- S17N (p.Ser17Asn), rs1041346574, gnomAD 9-127785874-G-A, CADD 15.50, SIFT 0.02
- S17S (p.Ser17Ser), rs1829294320, gnomAD 9-127785875-T-C, CADD 16.80
- p.Ser35 Gly41del, gnomAD 9-127785879-GGCGG, CADD 17.90
- p.Ser35dup, gnomAD 9-127785897-G-GGC, CADD 18.30
- S17L (p.Ser17Leu), rs1829296634, gnomAD 9-127785921-G-GC, CADD 21.00
- S17P (p.Ser17Pro), gnomAD 9-127785924-T-C, CADD 22.00, SIFT 0.03
- S17A (p.Ser17Ala), gnomAD 9-127785951-T-G, CADD 16.00, SIFT 0.04
- S17* (p.Ser17Ter), gnomAD 9-127785952-C-A, CADD 20.50
- Y19* (p.Tyr19Ter), TOPMed rs1378710886, gnomAD rs1378710886, CADD 33.00
- E20* (p.Glu20Ter), Ensembl rs1829310445, CADD 37.00
- L22F (p.Leu22Phe), ExAC rs770049111, TOPMed rs770049111, gnomAD rs770049111, REVEL 0.16, CADD 25.50
- L22V (p.Leu22Val), ExAC rs770049111, TOPMed rs770049111, gnomAD rs770049111, MetaLR 0.09, MetaSVM -1.06
- L22A (p.Leu22Ala), gnomAD 9-127785830-TCCGG, CADD 18.90
- L22I (p.Leu22Ile), gnomAD 9-127785843-C-A, CADD 19.70, SIFT 0.24
- L22P (p.Leu22Pro), rs938044629, gnomAD 9-127785844-T-C, CADD 21.90, SIFT 0.23
- L22L (p.Leu22Leu), rs1829293673, gnomAD 9-127785845-C-A, CADD 17.90
- A23T (p.Ala23Thr), gnomAD rs1427479508, CADD 20.10
- A23S (p.Ala23Ser), rs1289501621, gnomAD 9-127785834-G-T, CADD 19.50, SIFT 0.09
- A23P (p.Ala23Pro), gnomAD 9-127785834-G-C, CADD 19.20, SIFT 0.06
- A23E (p.Ala23Glu), gnomAD 9-127785835-C-A, CADD 17.90, SIFT 0.02
- A23V (p.Ala23Val), gnomAD 9-127785835-C-T, CADD 19.30, SIFT 0.13
- A23G (p.Ala23Gly), gnomAD 9-127785835-C-G, CADD 20.50, SIFT 0.10
- A23A (p.Ala23Ala), gnomAD 9-127785836-G-A, CADD 19.30
- A23R (p.Ala23Arg), gnomAD 9-127785844-TC-T, CADD 17.40
- A23D (p.Ala23Asp), gnomAD 9-127785865-C-A, CADD 19.40, SIFT 0.00
- A23* (p.Ala23Ter), gnomAD 9-127785868-CCG-C, CADD 16.90
- K24R (p.Lys24Arg), rs146765767, ClinGen CA200314047, ClinVar RCV004114168, ESP rs146765767, REVEL 0.33, CADD 26.80, Uncertain significance, not specified
- I25V (p.Ile25Val), gnomAD 9-127785858-A-G, CADD 21.50, SIFT 0.00
- I25L (p.Ile25Leu), gnomAD 9-127785858-A-C, CADD 21.20, SIFT 0.00
- I25F (p.Ile25Phe), gnomAD 9-127785858-A-T, CADD 21.30, SIFT 0.00
- I25T (p.Ile25Thr), gnomAD 9-127785859-T-C, CADD 21.20, SIFT 0.00
- I25S (p.Ile25Ser), gnomAD 9-127785859-T-G, CADD 21.10, SIFT 0.00
- I25I (p.Ile25Ile), rs1451045133, gnomAD 9-127785860-C-T, CADD 19.90
- G26W (p.Gly26Trp), gnomAD 9-127785861-G-T, CADD 19.80, SIFT 0.01
- G26R (p.Gly26Arg), rs2131825864, gnomAD 9-127785861-G-A, CADD 20.90, SIFT 0.03
- G26V (p.Gly26Val), gnomAD 9-127785862-G-T, CADD 19.80, SIFT 0.03
- G26E (p.Gly26Glu), gnomAD 9-127785862-G-A, CADD 20.20, SIFT 0.03
- G26G (p.Gly26Gly), gnomAD 9-127785863-G-A, CADD 17.10
- G28A (p.Gly28Ala), gnomAD 9-127785878-TG-T, CADD 17.60
- G28S (p.Gly28Ser), gnomAD 9-127785879-G-A, CADD 19.40, SIFT 0.00
- G28C (p.Gly28Cys), gnomAD 9-127785879-G-T, CADD 18.20, SIFT 0.00
- G28V (p.Gly28Val), gnomAD 9-127785880-G-T, CADD 18.30, SIFT 0.00
- G28D (p.Gly28Asp), gnomAD 9-127785880-G-A, CADD 18.60, SIFT 0.00
- G28G (p.Gly28Gly), gnomAD 9-127785881-C-A, CADD 15.80
- F30L (p.Phe30Leu), NCI-TCGA Cosmic COSV1009, MetaLR 0.20, MetaSVM -0.64, Variant assessed as somatic; moderate impact.
- p.Gly34 Gly41del, rs1336997122, gnomAD 9-127785878-TGGCG, CADD 18.80
- G31R (p.Gly31Arg), gnomAD 9-127785878-TGGCG, CADD 19.30
- p.Gly34dup, rs1375450424, gnomAD 9-127785878-T-TGG, CADD 17.90
- G31S (p.Gly31Ser), gnomAD 9-127785885-G-A, CADD 18.80, SIFT 0.41
- G31C (p.Gly31Cys), gnomAD 9-127785885-G-T, CADD 18.50, SIFT 0.13
- G31V (p.Gly31Val), gnomAD 9-127785886-G-T, CADD 18.30, SIFT 0.37
- G31D (p.Gly31Asp), gnomAD 9-127785886-G-A, CADD 18.60, SIFT 0.15
- G31G (p.Gly31Gly), gnomAD 9-127785887-C-T, CADD 19.20
- G31* (p.Gly31Ter), gnomAD 9-127785888-G-T, CADD 18.90
- G31E (p.Gly31Glu), rs1399602258, gnomAD 9-127785889-G-A, CADD 17.60, SIFT 0.00
- G31A (p.Gly31Ala), gnomAD 9-127785893-CG-C, CADD 17.30
- G31W (p.Gly31Trp), gnomAD 9-127785894-G-T, CADD 17.50, SIFT 0.00
- E32K (p.Glu32Lys), gnomAD rs1243073913, REVEL 0.52, CADD 33.00
- V33G (p.Val33Gly), Ensembl rs1588537476, REVEL 0.90, CADD 32.00
- V33L (p.Val33Leu), TOPMed rs1474729591, gnomAD rs1474729591, REVEL 0.84, CADD 27.10
- F34I (p.Phe34Ile), TOPMed rs1829328270, gnomAD rs1829328270, REVEL 0.61, CADD 28.80, Uncertain significance, not specified
- A36D (p.Ala36Asp), ExAC rs779167622, TOPMed rs779167622, gnomAD rs779167622, REVEL 0.76, CADD 28.60, Uncertain significance
- A36G (p.Ala36Gly), ExAC rs779167622, TOPMed rs779167622, gnomAD rs779167622, REVEL 0.40, CADD 29.60, Uncertain significance, not specified
- R37G (p.Arg37Gly), TOPMed rs988782815, REVEL 0.29, CADD 29.30
- R37W (p.Arg37Trp), rs1466530561, gnomAD 9-127785804-C-T, CADD 18.80, SIFT 0.00
- R37R (p.Arg37Arg), gnomAD 9-127785804-C-A, CADD 18.40
- R37Q (p.Arg37Gln), gnomAD 9-127785805-G-A, CADD 18.30, SIFT 0.00
- R37L (p.Arg37Leu), rs1325740412, gnomAD 9-127785805-G-T, CADD 17.90, SIFT 0.00
- R37P (p.Arg37Pro), gnomAD 9-127785815-A-AC, CADD 16.40
- R37E (p.Arg37Glu), gnomAD 9-127785815-AC-A, CADD 16.00
- R37* (p.Arg37Ter), gnomAD 9-127785819-C-T, CADD 16.80
- p.Arg15 Pro48del, gnomAD 9-127785825-CCAGC, CADD 18.70
- R39C (p.Arg39Cys), gnomAD rs1283944680, REVEL 0.40, CADD 28.60
- R39P (p.Arg39Pro), TOPMed rs914635422, gnomAD rs914635422, REVEL 0.41, CADD 28.60
- K40E (p.Lys40Glu), gnomAD rs1292765835
- K40Q (p.Lys40Gln), gnomAD rs1292765835, REVEL 0.09, CADD 14.80
- T41S (p.Thr41Ser), TOPMed rs905857521, REVEL 0.20, CADD 22.40
- G42V (p.Gly42Val), ExAC rs747453571, TOPMed rs747453571, gnomAD rs747453571, REVEL 0.46, CADD 23.30
- G41del (p.Gly41del), rs1012795846, gnomAD 9-127785900-AGCG-, CADD 19.80
- p.Gly41dup, rs1012795846, gnomAD 9-127785900-A-AGC, CADD 19.00
- G42R (p.Gly42Arg), gnomAD 9-127785900-AGCGG, CADD 19.20
- G42A (p.Gly42Ala), gnomAD 9-127785904-GC-G, CADD 21.10
- G42S (p.Gly42Ser), rs1260406352, gnomAD 9-127785906-G-A, CADD 19.30, SIFT 0.41
- G42C (p.Gly42Cys), gnomAD 9-127785906-G-T, CADD 19.00, SIFT 0.13
- G42D (p.Gly42Asp), gnomAD 9-127785907-G-A, CADD 19.10, SIFT 0.15
- G42G (p.Gly42Gly), rs1200278242, gnomAD 9-127785908-C-A, CADD 16.70
- G42E (p.Gly42Glu), gnomAD 9-127785913-GC-G, CADD 22.40
- G42* (p.Gly42Ter), gnomAD 9-127785915-G-T, CADD 19.50
- V45G (p.Val45Gly), Ensembl rs1588537494, MetaLR 0.56, MetaSVM 0.39
- A46G (p.Ala46Gly), gnomAD 9-127785915-GGAGG, CADD 19.30
- A46S (p.Ala46Ser), gnomAD 9-127785921-G-T, CADD 19.20, SIFT 0.46
- A46T (p.Ala46Thr), gnomAD 9-127785921-G-A, CADD 19.40, SIFT 0.00
- A46D (p.Ala46Asp), rs1454104231, gnomAD 9-127785922-C-A, CADD 19.30, SIFT 0.00
- A46V (p.Ala46Val), rs1454104231, gnomAD 9-127785922-C-T, CADD 20.00, SIFT 0.00
- A46A (p.Ala46Ala), rs1014923565, gnomAD 9-127785923-C-A, CADD 19.40
- A46E (p.Ala46Glu), gnomAD 9-127785928-C-A, CADD 19.50, SIFT 0.00
- A46P (p.Ala46Pro), rs1382604012, gnomAD 9-127785930-G-C, CADD 20.40, SIFT 0.02
- K49E (p.Lys49Glu), TOPMed rs1829328967
- V50G (p.Val50Gly), gnomAD rs761040673, REVEL 0.82, CADD 32.00
- L51F (p.Leu51Phe), gnomAD 9-127785948-C-T, CADD 19.10, SIFT 0.00
- L51H (p.Leu51His), gnomAD 9-127785949-T-A, CADD 19.70, SIFT 0.00
- L51P (p.Leu51Pro), rs1829298312, gnomAD 9-127785949-T-C, CADD 20.30, SIFT 0.00
- L51L (p.Leu51Leu), rs794728003, gnomAD 9-127785950-C-G, CADD 18.40
- M52V (p.Met52Val), NCI-TCGA TCGA novel, MetaLR 0.15, MetaSVM -0.92, Variant assessed as somatic; moderate impact.
- N54H (p.Asn54His), Ensembl rs1375660584
- N54K (p.Asn54Lys), NCI-TCGA TCGA novel, MetaLR 0.11, MetaSVM -1.09, Variant assessed as somatic; high impact.
- N54S (p.Asn54Ser), TOPMed rs1829329177, gnomAD rs1829329177, REVEL 0.29, CADD 23.20
- E57D (p.Glu57Asp), NCI-TCGA TCGA novel, REVEL 0.23, CADD 23.50, Variant assessed as somatic; moderate impact.
- G58R (p.Gly58Arg), rs149950953, ClinGen CA5251620, ClinVar RCV004430945, ESP rs149950953, REVEL 0.67, CADD 32.00, Uncertain significance, not specified
- G58W (p.Gly58Trp), ESP rs149950953, ExAC rs149950953, gnomAD rs149950953, REVEL 0.73, CADD 33.00, Uncertain significance
- G58V (p.Gly58Val), gnomAD 9-127785955-G-T, CADD 21.30, SIFT 0.00
- G58A (p.Gly58Ala), gnomAD 9-127785955-G-C, CADD 19.40, SIFT 0.01
- G58E (p.Gly58Glu), rs1264216054, gnomAD 9-127785955-G-A, CADD 19.70, SIFT 0.00
- G58G (p.Gly58Gly), gnomAD 9-127785956-A-G, CADD 21.00
- G58S (p.Gly58Ser), gnomAD 9-127785978-G-A, CADD 19.70, SIFT 0.01
- G58D (p.Gly58Asp), gnomAD 9-127785979-G-A, CADD 19.80, SIFT 0.01
- G58C (p.Gly58Cys), gnomAD 9-127785981-G-T, CADD 19.10, SIFT 0.00
- p.Gly70dup, gnomAD 9-127786003-C-CGG, CADD 19.40
- F59L (p.Phe59Leu), rs55640715, UniProt VAR 041982, ESP rs55640715, ExAC rs55640715, REVEL 0.21, CADD 23.70
- P60R (p.Pro60Arg), gnomAD rs1466578290, REVEL 0.47, CADD 26.10
- P60S (p.Pro60Ser), NCI-TCGA Cosmic COSV6472, CADD 19.70, Variant assessed as somatic; moderate impact.
- P60T (p.Pro60Thr), gnomAD 9-127785933-C-A, CADD 17.50, SIFT 0.00
- P60A (p.Pro60Ala), rs994921744, gnomAD 9-127785933-C-G, CADD 17.50, SIFT 0.00
- P60L (p.Pro60Leu), gnomAD 9-127785934-C-T, CADD 20.90, SIFT 0.00
- P60Q (p.Pro60Gln), rs1829297506, gnomAD 9-127785934-C-A, CADD 21.10, SIFT 0.00
- P60P (p.Pro60Pro), gnomAD 9-127785935-G-A, CADD 19.00
- P60H (p.Pro60His), rs986342846, gnomAD 9-127785940-C-A, CADD 19.30, SIFT 0.00
Public CDK9 analysis runs
- CDK9 analysis run — CDK9 (581 variants) — completed 2026-08-20