CDK6

Chr 7AR

cyclin dependent kinase 6

ENSG00000105810 UniProt: Q00534 OMIM: 603368

CDK6 encodes a serine/threonine kinase that phosphorylates the retinoblastoma protein to promote G1/S cell cycle transition and is essential for neuronal proliferation in the hippocampus and brain ventricular zones. Mutations cause primary microcephaly 12 with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.98), reflecting its critical role in neurodevelopment.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

ARLOEUF 0.281 OMIM phenotype

Clinical Summary— CDK6

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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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Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.28LOEUF

pLI 0.983

Z-score 3.58

OE 0.06 (0.02–0.28)

Highly constrained

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

Missense Constraint

3.06Z-score

OE missense 0.37 (0.31–0.45)

70 obs / 188.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios

LoF OE0.06 (0.02–0.28)

0≤0.351.4

Missense OE0.37 (0.31–0.45)

0≤0.61.4

Synonymous OE0.92

0≤1.21.6

LoF obs/exp: 1 / 16.8Missense obs/exp: 70 / 188.1Syn Z: 0.54

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CDK6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

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

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

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

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

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

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

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