CDK6 (Cyclin-dependent kinase 6) variants and mutations
CDK6 (also known as Cyclin-dependent kinase 6) is a human protein-coding gene encoding a cyclin-dependent kinase 6 protein. It works with D-type cyclins to relieve RB-mediated cell-cycle restraint and also has lineage-specific transcriptional functions in hematopoietic cells. Excess activity contributes to many cancers and is therapeutically targeted together with CDK4. This analysis covers 1,406 CDK6 variants and mutations. Of these, 52% have computational variant effect predictions. Disease context includes breast cancer, small cell lung carcinoma, and breast carcinoma. Example CDK6 variants include M1?, E2*, and E2Q.
Variant analysis overview
- Gene: CDK6
- Protein: Cyclin-dependent kinase 6
- UniProt accession: Q00534
- Organism: Homo sapiens
- Variants analyzed: 1406
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,274 unspecified-consequence records; 71 synonymous variants; 7 frameshift variants; 45 missense variants; 6 splice-region variants; 1 in-frame deletions; 2 stop-gained variants
- Prediction scores: 737 variants have prediction scores (52% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: breast cancer, small cell lung carcinoma, breast carcinoma, neoplasm, breast neoplasm, autosomal recessive primary microcephaly, neurodegenerative disease, Behcet disease, prostate adenocarcinoma, clear cell renal carcinoma, hypothyroidism, HER2 positive breast carcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 8 post-translational modification sites.
- Structural context: 1,241 variants have structural context.
- PTM context: 31 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 CDK6 variants
Examples include M1?, E2*, E2Q, K3E, D4A, D4E, D4G, D4N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV56010
- E2* (p.Glu2Ter), Ensembl rs2116035008, CADD 36.00
- E2Q (p.Glu2Gln), Ensembl rs2116035008, MetaLR 0.18, MetaSVM -1.01
- K3E (p.Lys3Glu), Ensembl rs2116034995, REVEL 0.11, MetaLR 0.13
- D4A (p.Asp4Ala), Ensembl rs2116034964
- D4E (p.Asp4Glu), TOPMed rs937148501, gnomAD rs937148501, REVEL 0.07, MetaLR 0.18
- D4G (p.Asp4Gly), cosmic curated COSV10584, Ensembl rs2116034964, REVEL 0.24, MetaLR 0.23
- D4N (p.Asp4Asn), cosmic curated COSV56015
- D4V (p.Asp4Val), Ensembl rs2116034964, MetaLR 0.23, MetaSVM -0.76
- G5C (p.Gly5Cys), 1000Genomes rs576150359, ExAC rs576150359, gnomAD rs576150359, REVEL 0.22, MetaLR 0.21
- G5D (p.Gly5Asp), Ensembl rs2116034905, REVEL 0.14, MetaLR 0.26
- G5R (p.Gly5Arg), 1000Genomes rs576150359, ExAC rs576150359, gnomAD rs576150359, REVEL 0.11, MetaLR 0.20
- G5S (p.Gly5Ser), cosmic curated COSV56014, 1000Genomes rs576150359, ExAC rs576150359, gnomAD rs576150359, REVEL 0.07, MetaLR 0.16
- L6P (p.Leu6Pro), Ensembl rs2116034852, REVEL 0.13, MetaLR 0.17
- L6Q (p.Leu6Gln), Ensembl rs2116034852, REVEL 0.24, MetaLR 0.20
- L6R (p.Leu6Arg), cosmic curated COSV10722, REVEL 0.25, MetaLR 0.17
- L6V (p.Leu6Val), 1000Genomes rs556194182, ExAC rs556194182, TOPMed rs556194182, gnomAD rs556194182, REVEL 0.06, MetaLR 0.18
- C7S (p.Cys7Ser), Ensembl rs2116034828, REVEL 0.20, MetaLR 0.18
- C7W (p.Cys7Trp), TOPMed rs1464756248, gnomAD rs1464756248, REVEL 0.08, MetaLR 0.24
- R8C (p.Arg8Cys), NCI-TCGA Cosmic COSV5601, cosmic curated COSV56011, TOPMed rs1801541400, gnomAD rs1801541400, REVEL 0.38, MetaLR 0.17, Variant assessed as somatic; moderate impact.
- R8H (p.Arg8His), TOPMed rs1801541322, gnomAD rs1801541322, REVEL 0.14, MetaLR 0.16
- R8P (p.Arg8Pro), TOPMed rs1801541322, gnomAD rs1801541322, MetaLR 0.19, MetaSVM -0.86
- R8S (p.Arg8Ser), TOPMed rs1801541400, gnomAD rs1801541400, REVEL 0.34, MetaLR 0.11
- A9G (p.Ala9Gly), Ensembl rs2116034721
- A9P (p.Ala9Pro), rs2116034735, ClinGen CA368386834, ClinVar RCV004430937, Ensembl rs2116034735, AlphaMissense 0.12, MetaLR 0.10, Uncertain significance, not specified
- A9T (p.Ala9Thr), Ensembl rs2116034735, REVEL 0.09, AlphaMissense 0.12, Uncertain significance
- A9V (p.Ala9Val), Ensembl rs2116034721, REVEL 0.09, MetaLR 0.04
- D10E (p.Asp10Glu), Ensembl rs2116034653
- D10G (p.Asp10Gly), Ensembl rs1230241694
- D10N (p.Asp10Asn), Ensembl rs2116034685
- D10V (p.Asp10Val), Ensembl rs1230241694, MetaLR 0.05, MetaSVM -1.09
- Q11* (p.Gln11Ter), Ensembl rs2116034611, CADD 37.00
- Q11H (p.Gln11His), Ensembl rs2116034580, REVEL 0.08, MetaLR 0.07
- Q11K (p.Gln11Lys), Ensembl rs2116034611, REVEL 0.15, MetaLR 0.07
- Q11R (p.Gln11Arg), ExAC rs755309013, gnomAD rs755309013, REVEL 0.06, MetaLR 0.07
- Q12* (p.Gln12Ter), NCI-TCGA TCGA novel, Ensembl rs2116034560, Variant assessed as somatic; high impact.
- Q12E (p.Gln12Glu), Ensembl rs2116034560
- Q12H (p.Gln12His), Ensembl rs2116034537
- Y13* (p.Tyr13Ter), 1000Genomes rs538142754, ExAC rs538142754, TOPMed rs538142754, gnomAD rs538142754, CADD 34.00
- Y13C (p.Tyr13Cys), Ensembl rs2116034498
- Y13D (p.Tyr13Asp), Ensembl rs2116034519, REVEL 0.64, MetaLR 0.53
- Y13F (p.Tyr13Phe), Ensembl rs2116034498
- Y13N (p.Tyr13Asn), Ensembl rs2116034519
- E14* (p.Glu14Ter), ExAC rs766582975, TOPMed rs766582975, gnomAD rs766582975
- E14K (p.Glu14Lys), ExAC rs766582975, TOPMed rs766582975, gnomAD rs766582975, REVEL 0.37, MetaLR 0.26
- E14Q (p.Glu14Gln), ExAC rs766582975, TOPMed rs766582975, gnomAD rs766582975, REVEL 0.34, MetaLR 0.23
- E14V (p.Glu14Val), Ensembl rs2116034442, MetaLR 0.23, MetaSVM -0.80
- C15G (p.Cys15Gly), ExAC rs758530954, gnomAD rs758530954
- C15R (p.Cys15Arg), ExAC rs758530954, gnomAD rs758530954, REVEL 0.15, MetaLR 0.03
- C15S (p.Cys15Ser), ExAC rs758530954, gnomAD rs758530954
- C15W (p.Cys15Trp), TOPMed rs1801540663, MetaLR 0.04, MetaSVM -1.09
- V16E (p.Val16Glu), Ensembl rs2116034319
- V16M (p.Val16Met), TOPMed rs1445849101, gnomAD rs1445849101, REVEL 0.25, MetaLR 0.23
- A17G (p.Ala17Gly), Ensembl rs2116034248, REVEL 0.39, MetaLR 0.13
- A17S (p.Ala17Ser), Ensembl rs2116034274, REVEL 0.32, MetaLR 0.10
- A17V (p.Ala17Val), Ensembl rs2116034248, MetaLR 0.10, MetaSVM -0.95
- E18G (p.Glu18Gly), Ensembl rs2116034185, REVEL 0.69, MetaLR 0.42
- E18K (p.Glu18Lys), NCI-TCGA Cosmic COSV5600, NCI-TCGA Cosmic COSV5601, cosmic curated COSV56010, Ensembl rs2116034204, REVEL 0.42, MetaLR 0.19, Variant assessed as somatic; moderate impact.
- E18Q (p.Glu18Gln), NCI-TCGA Cosmic COSV5600, cosmic curated COSV56006, NCI-TCGA Cosmic COSV5601, Variant assessed as somatic; moderate impact.
- E18V (p.Glu18Val), cosmic curated COSV56006, Ensembl rs2116034185, MetaLR 0.33, MetaSVM -0.36
- I19F (p.Ile19Phe), Ensembl rs2116034159
- I19L (p.Ile19Leu), Ensembl rs2116034159, REVEL 0.27, MetaLR 0.12
- I19M (p.Ile19Met), TOPMed rs1801540467, gnomAD rs1801540467, REVEL 0.43, MetaLR 0.33
- I19N (p.Ile19Asn), Ensembl rs2116034133
- I19S (p.Ile19Ser), Ensembl rs2116034133
- I19T (p.Ile19Thr), Ensembl rs2116034133
- I19V (p.Ile19Val), Ensembl rs2116034159, MetaLR 0.33, MetaSVM -0.41
- G20E (p.Gly20Glu), Ensembl rs2116034049
- G20R (p.Gly20Arg), gnomAD rs1243253602
- G20V (p.Gly20Val), Ensembl rs2116034049, MetaLR 0.83, MetaSVM 0.90
- E21* (p.Glu21Ter), 1000Genomes rs1199476203, TOPMed rs1199476203, gnomAD rs1199476203, CADD 36.00
- E21D (p.Glu21Asp), Ensembl rs2116033963
- E21K (p.Glu21Lys), 1000Genomes rs1199476203, TOPMed rs1199476203, gnomAD rs1199476203, REVEL 0.27, MetaLR 0.11
- E21V (p.Glu21Val), Ensembl rs2116033984, MetaLR 0.17, MetaSVM -0.84
- G22R (p.Gly22Arg), Ensembl rs2116033933
- G22S (p.Gly22Ser), Ensembl rs2116033933, REVEL 0.96, MetaLR 0.96
- A23G (p.Ala23Gly), Ensembl rs2116033868
- A23S (p.Ala23Ser), Ensembl rs2116033888, MetaLR 0.30, MetaSVM -0.47
- A23V (p.Ala23Val), Ensembl rs2116033868, REVEL 0.56, MetaLR 0.36
- Y24C (p.Tyr24Cys), TOPMed rs1003962156, gnomAD rs1003962156, REVEL 0.59, MetaLR 0.32
- Y24F (p.Tyr24Phe), TOPMed rs1003962156, gnomAD rs1003962156
- Y24H (p.Tyr24His), Ensembl rs2116033808
- Y24N (p.Tyr24Asn), Ensembl rs2116033808
- Y24S (p.Tyr24Ser), TOPMed rs1003962156, gnomAD rs1003962156, MetaLR 0.32, MetaSVM -0.38
- G25A (p.Gly25Ala), Ensembl rs2116033739
- G25E (p.Gly25Glu), Ensembl rs2116033739
- G25R (p.Gly25Arg), TOPMed rs1265110568
- G25V (p.Gly25Val), cosmic curated COSV56008, REVEL 0.71, MetaLR 0.66
- K26M (p.Lys26Met), NCI-TCGA TCGA novel, Ensembl rs2116033701, MetaLR 0.39, MetaSVM -0.18, Variant assessed as somatic; moderate impact.
- K26R (p.Lys26Arg), Ensembl rs2116033701, REVEL 0.16, MetaLR 0.17
- V27E (p.Val27Glu), Ensembl rs1584132732
- V27G (p.Val27Gly), Ensembl rs1584132732, REVEL 0.77, MetaLR 0.69
- V27M (p.Val27Met), Ensembl rs2116033673, REVEL 0.69, MetaLR 0.66
- F28C (p.Phe28Cys), Ensembl rs2116033613
- F28I (p.Phe28Ile), Ensembl rs2116033632
- F28L (p.Phe28Leu), Ensembl rs2116033632, REVEL 0.41, MetaLR 0.22
- F28S (p.Phe28Ser), Ensembl rs2116033613
- F28V (p.Phe28Val), Ensembl rs2116033632
- F28Y (p.Phe28Tyr), Ensembl rs2116033613, MetaLR 0.08, MetaSVM -0.99
- K29E (p.Lys29Glu), Ensembl rs2116033589, REVEL 0.57, MetaLR 0.34
- K29M (p.Lys29Met), Ensembl rs2116033570
- K29N (p.Lys29Asn), gnomAD rs1353455975
- K29R (p.Lys29Arg), Ensembl rs2116033570, MetaLR 0.38, MetaSVM -0.30
- A30G (p.Ala30Gly), Ensembl rs2116033504
- A30P (p.Ala30Pro), Ensembl rs2116033525
- A30S (p.Ala30Ser), Ensembl rs2116033525, REVEL 0.42, MetaLR 0.32
- A30V (p.Ala30Val), Ensembl rs2116033504, MetaLR 0.26, MetaSVM -0.58
- R31C (p.Arg31Cys), Ensembl rs2116033461
- R31G (p.Arg31Gly), Ensembl rs2116033461
- R31H (p.Arg31His), Ensembl rs2116033439
- R31L (p.Arg31Leu), Ensembl rs2116033439
- R31P (p.Arg31Pro), Ensembl rs2116033439, MetaLR 0.33, MetaSVM -0.28
- R31S (p.Arg31Ser), Ensembl rs2116033461, REVEL 0.52, MetaLR 0.21
- D32A (p.Asp32Ala), Ensembl rs2116033398
- D32E (p.Asp32Glu), Ensembl rs2116033382
- D32H (p.Asp32His), Ensembl rs2116033416
- D32N (p.Asp32Asn), Ensembl rs2116033416
- D32V (p.Asp32Val), Ensembl rs2116033398, MetaLR 0.51, MetaSVM 0.11
- L33* (p.Leu33Ter), Ensembl rs2116033340
- L33M (p.Leu33Met), Ensembl rs2116033359
- L33S (p.Leu33Ser), Ensembl rs2116033340
- K34E (p.Lys34Glu), Ensembl rs2116033308
- K34M (p.Lys34Met), Ensembl rs2116033279, MetaLR 0.29, MetaSVM -0.60
- K34R (p.Lys34Arg), Ensembl rs2116033279, REVEL 0.23, MetaLR 0.17
- N35I (p.Asn35Ile), Ensembl rs2116033226
- N35K (p.Asn35Lys), gnomAD rs1248846198, REVEL 0.20, MetaLR 0.04
- N35S (p.Asn35Ser), Ensembl rs2116033226
- N35T (p.Asn35Thr), Ensembl rs2116033226, MetaLR 0.03, MetaSVM -1.06
- G36A (p.Gly36Ala), gnomAD rs1383556587, MetaLR 0.19, MetaSVM -0.83
- G36E (p.Gly36Glu), gnomAD rs1383556587, REVEL 0.18, MetaLR 0.17
- G36R (p.Gly36Arg), Ensembl rs2116033196, REVEL 0.25, MetaLR 0.14
- G37A (p.Gly37Ala), Ensembl rs2116033119
- G37C (p.Gly37Cys), TOPMed rs1011187353
- G37S (p.Gly37Ser), TOPMed rs1011187353
- G37V (p.Gly37Val), Ensembl rs2116033119, REVEL 0.36, MetaLR 0.37
- R38G (p.Arg38Gly), ExAC rs759338099, gnomAD rs759338099, REVEL 0.35, MetaLR 0.22
- F39V (p.Phe39Val), Ensembl rs2116033035, REVEL 0.41, MetaLR 0.19
- F39Y (p.Phe39Tyr), Ensembl rs2116033020, MetaLR 0.23, MetaSVM -0.62
- V40A (p.Val40Ala), Ensembl rs2116032959
- V40E (p.Val40Glu), Ensembl rs2116032959
- V40G (p.Val40Gly), Ensembl rs2116032959
- V40L (p.Val40Leu), Ensembl rs2116032987
- V40M (p.Val40Met), Ensembl rs2116032987
- A41P (p.Ala41Pro), cosmic curated COSV99720, Ensembl rs2116032915
- A41S (p.Ala41Ser), Ensembl rs2116032915, MetaLR 0.77, MetaSVM 0.85
- L42* (p.Leu42Ter), Ensembl rs2116032856
- L42F (p.Leu42Phe), Ensembl rs2116032827
- L42M (p.Leu42Met), Ensembl rs2116032874
- L42S (p.Leu42Ser), Ensembl rs2116032856
- L42V (p.Leu42Val), cosmic curated COSV56010, Ensembl rs2116032874
- L42W (p.Leu42Trp), Ensembl rs2116032856, MetaLR 0.53, MetaSVM 0.14
- K43M (p.Lys43Met), Ensembl rs2116032811
- K43N (p.Lys43Asn), Ensembl rs2116032793, REVEL 0.70, MetaLR 0.81
- K43R (p.Lys43Arg), Ensembl rs2116032811, MetaLR 0.83, MetaSVM 0.86
- R44C (p.Arg44Cys), cosmic curated COSV10505, Ensembl rs2116032766, REVEL 0.21, MetaLR 0.08
- R44G (p.Arg44Gly), Ensembl rs2116032766
- R44H (p.Arg44His), Ensembl rs2116032738
- R44P (p.Arg44Pro), Ensembl rs2116032738
- R44S (p.Arg44Ser), Ensembl rs2116032766
- V45A (p.Val45Ala), Ensembl rs2116032686
- V45E (p.Val45Glu), Ensembl rs2116032686
- V45G (p.Val45Gly), Ensembl rs2116032686, MetaLR 0.57, MetaSVM 0.29
- V45L (p.Val45Leu), ExAC rs774217237, TOPMed rs774217237, gnomAD rs774217237, REVEL 0.28, MetaLR 0.11
- V45M (p.Val45Met), NCI-TCGA TCGA novel, REVEL 0.45, MetaLR 0.29, Variant assessed as somatic; moderate impact.
- R46G (p.Arg46Gly), gnomAD rs1290397698
- R46L (p.Arg46Leu), Ensembl rs2116032630
- R46P (p.Arg46Pro), Ensembl rs2116032630
- R46Q (p.Arg46Gln), Ensembl rs2116032630, MetaLR 0.31, MetaSVM -0.39
- R46W (p.Arg46Trp), cosmic curated COSV56011, gnomAD rs1290397698, REVEL 0.48, MetaLR 0.43
- V47M (p.Val47Met), Ensembl rs1052620651
- Q48E (p.Gln48Glu), Ensembl rs2116032554
- Q48H (p.Gln48His), ExAC rs748860173, gnomAD rs748860173, REVEL 0.23, MetaLR 0.12
- Q48L (p.Gln48Leu), gnomAD rs1359663998, MetaLR 0.15, MetaSVM -0.78
- Q48R (p.Gln48Arg), gnomAD rs1359663998, REVEL 0.34, MetaLR 0.16
- T49A (p.Thr49Ala), Ensembl rs2116032480
- T49I (p.Thr49Ile), Ensembl rs2116032466
- T49P (p.Thr49Pro), Ensembl rs2116032480
- T49S (p.Thr49Ser), Ensembl rs2116032480, MetaLR 0.11, MetaSVM -0.93
- G50C (p.Gly50Cys), TOPMed rs1368516053, gnomAD rs1368516053, REVEL 0.21, MetaLR 0.22
- G50D (p.Gly50Asp), cosmic curated COSV56013, Ensembl rs2116032410
Public CDK6 analysis runs
- CDK6 analysis run — CDK6 (1,406 variants) — completed 2026-08-18