CDK6

Chr 7AR

cyclin dependent kinase 6

Also known as: MCPH12, PLSTIRE

The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. [provided by RefSeq, Aug 2017]

GeneReviewsOMIMResearchGenerating clinical summary…
ARLOEUF 0.281 OMIM phenotype
Clinical SummaryCDK6
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 12 VUS of 51 total submissions
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — CDK6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.28LOEUF
pLI 0.983
Z-score 3.58
OE 0.06 (0.020.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.06Z-score
OE missense 0.37 (0.310.45)
70 obs / 188.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.06 (0.020.28)
00.351.4
Missense OE?0.37 (0.310.45)
00.61.4
Synonymous OE?0.92
01.21.6
LoF obs/exp: 1 / 16.8Missense obs/exp: 70 / 188.1Syn Z: 0.54

ClinVar Variant Classifications

51 submitted variants in ClinVar

Classification Summary

Pathogenic1
VUS12
Likely Benign12
Benign14
Conflicting1
1
Pathogenic
12
VUS
12
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
12
0
0
12
Likely Benign
0
1
1
10
12
Benign
0
0
12
2
14
Conflicting
1
Total014131240

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap CDK6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CDK6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Advanced LymphomaAdvanced Malignant Solid NeoplasmRefractory Lymphoma

Testing Palbociclib (PD-0332991) as Potentially Targeting Treatment in Cancers With CDK4 or CDK6 Amplification (MATCH - Subprotocol Z1C)

ACTIVE NOT RECRUITING
NCT06390839Phase PHASE2National Cancer Institute (NCI)Started 2017-03-22
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Breast Neoplasms

Tailoring NEOadjuvant Therapy in Hormone Receptor Positive, HER2 Negative, Luminal Breast Cancer.

ACTIVE NOT RECRUITING
NCT03283384Phase PHASE2Borstkanker Onderzoek GroepStarted 2019-06-15
LetrozoleChemotherapyRibociclib plus letrozole
NSCLC

A Study With BPI-1178 and Osimertinib in Advanced Non-small Cell Lung Cancer Patients With EGFR Mutations

RECRUITING
NCT06362980Phase PHASE1National Cancer Center, ChinaStarted 2024-05-22
BPI-1178Osimertinib
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING
NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14
PalbociclibSunitinibTemsirolimus
Cancer

Study of the CDK4/6 Inhibitor Abemaciclib in Solid Tumors Harboring Genetic Alterations in Genes Encoding D-Type Cyclins or Amplification of CDK4 or CDK6

RECRUITING
NCT03310879Phase PHASE2Dana-Farber Cancer InstituteStarted 2017-11-21
Abemaciclib
CDK4/6 InhibitorBreast CancerCYP3A4 Protein, Human

Pharmacogenomic and Circulating Biomarkers for CDK4/6 Inhibitors

ENROLLING BY INVITATION
NCT07100054London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sStarted 2025-10-10
Whole gene sequencingDrug-drug interaction analysisBiomarker analysis
Anatomic Stage IV Breast Cancer AJCC v8Metastatic HER2-Negative Breast CarcinomaMetastatic Hormone Receptor-Positive Breast Carcinoma

A Vaccine (STEMVAC) With Standard Endocrine-Based Therapy or Chemotherapy for the Treatment of Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

RECRUITING
NCT07112053Phase PHASE2University of WashingtonStarted 2025-11-17
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineCapecitabineComputed Tomography