CDK4
Chr 12cyclin dependent kinase 4
Also known as: CMM3, MCPH31, PSK-J3
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]
Primary Disease Associations & Inheritance
Clinical highlights
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CDK4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Multigene Risk Score Combined With Ki-67 Dynamic Assessment in Stratified Neoadjuvant Endocrine Therapy Treatment With or Without CDK4/6 Inhibitors in HR+/HER2- Breast Cancer
ENROLLING BY INVITATIONA Model for Genetic Susceptibility: Melanoma
ACTIVE NOT RECRUITINGPharmacogenomic and Circulating Biomarkers for CDK4/6 Inhibitors
ENROLLING BY INVITATIONGenomic and Transcriptomic Predictors of Sequential SG Sensitivity After T-DXd in ER+/HER2-Low Metastatic Breast Cancer
RECRUITINGFirst-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer
RECRUITINGElacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)
RECRUITINGAn Open-Label, Bayesian Adaptive Phase II Clinical Study in HR+/HER2- Advanced Breast Cancer After Progression on Standard Therapy
RECRUITINGHigh Definition Medicine for Solid Tumors Oncology
RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
ACTIVE NOT RECRUITINGElacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i.
RECRUITINGCapivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
ACTIVE NOT RECRUITINGAnalysis of Circulating Tumor mArkers in Blood 4 - ALCINA 4
RECRUITINGExternal Resources
Links to major genomics databases and tools