CDK6

Oncogene
Cyclin-dependent kinase 6 UniProt accession Q00534

Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle.

Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development.

Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors.

Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663)

Source: UniProt

Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 (By similarity). Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c.

Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels

Source: UniProt
Cytoplasm, Nucleus, Cell projection, ruffle, Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Source: UniProt

Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells

Source: UniProt
  • Microcephaly 12, primary, autosomal recessive (MCPH12)

    A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.

Source: UniProt
  • Oxidative Stress Induced Senescence
  • Senescence-Associated Secretory Phenotype (SASP)
  • Oncogene Induced Senescence
  • Cyclin D associated events in G1
  • Regulation of RUNX1 Expression and Activity
  • Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
  • Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
  • Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
  • Drug-mediated inhibition of CDK4/CDK6 activity
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.28%
Lung Adenocarcinoma 0.44%
Lung Small Cell Carcinoma 1.19%
Lung Squamous Cell Carcinoma 0.54%
Oesophagus Adenocarcinoma 2.48%
Pancreas Ductal Carcinoma 0.41%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CDK6, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 12

NCT ID Condition Brief Title Phase Status
NCT03434262 Anaplastic Astrocytoma, Anaplastic Ependymoma, Anaplastic Ganglioglioma, Anaplastic Meningioma, Anaplastic Oligodendroglioma, Pleomorphic Xanthoastrocytoma, Anaplastic, Atypical Teratoid/Rhabdoid Tumor, Brain Cancer, Brain Tumor, Central Nervous System Neoplasms, Choroid Plexus Carcinoma, CNS Embryonal Tumor With Rhabdoid Features, Ganglioneuroblastoma of Central Nervous System, CNS Tumor, Embryonal Tumor of CNS, Ependymoma, Glioblastoma, Glioma, Glioma, Malignant, Medulloblastoma, Medulloblastoma; Unspecified Site, Medulloepithelioma, Neuroepithelial Tumor, Neoplasms, Neoplasms, Neuroepithelial, Papillary Tumor of the Pineal Region (High-grade Only), Pediatric Brain Tumor, Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only), Pineoblastoma, Primitive Neuroectodermal Tumor, Recurrent Medulloblastoma, Refractory Brain Tumor, Neuroblastoma. CNS, Glioblastoma, IDH-mutant, Glioblastoma, IDH-wildtype, Medulloblastoma, Group 3, Medulloblastoma, Group 4, Glioma, High Grade, Neuroepithelial Tumor, High Grade, Medulloblastoma, SHH-activated and TP53 Mutant, Medulloblastoma, SHH-activated and TP53 Wildtype, Medulloblastoma, Chromosome 9q Loss, Medulloblastoma, Non-WNT Non-SHH, NOS, Medulloblastoma, Non-WNT/Non-SHH, Medulloblastoma, PTCH1 Mutation, Medulloblastoma, WNT-activated, Ependymoma, Recurrent, Glioma, Recurrent High Grade, Glioma, Recurrent Malignant, Embryonal Tumor, NOS, Glioma, Diffuse Midline, H3K27M-mutant, Embryonal Tumor With Multilayered Rosettes (ETMR), Ependymoma, NOS, WHO Grade III, Ependymoma, NOS, WHO Grade II, Medulloblastoma, G3/G4, Ependymoma, RELA Fusion Positive SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors PHASE1 COMPLETED
NCT05288166 Prostatic Neoplasms, Neoplasm Metastasis, Urogenital Neoplasms, Physiological Effects of Drugs, Antineoplastic Agents, Antineoplastic Agents, Hormonal, Androgens, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Abiraterone Acetate, Steroid Synthesis Inhibitors, Cytochrome P-450, Enzyme Inhibitors, Prednisone, Prednisolone, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6 A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer) PHASE3 ACTIVE_NOT_RECRUITING
NCT04707196 Breast Neoplasms, Neoplasm Metastasis A Study of Abemaciclib in Indian Women With Advanced Breast Cancer PHASE4 COMPLETED
NCT02278120 Advanced Metastatic Breast Cancer Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer PHASE3 COMPLETED
NCT05935748 ccRCC, Clear Cell Renal Cell Carcinoma, Kidney Cancer, Kidney Neoplasms, Renal Cancer, Renal Neoplasms, Recurrent Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Refractory Renal Cell Carcinoma, Advanced Renal Cell Carcinoma, Carcinoma, Neoplasms, Carcinoma, Renal Cell, Neoplasms, Glandular and Epithelial, Neoplasm by Histology, Adenocarcinoma, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Kidney Diseases, Urologic Diseases Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc) PHASE2 TERMINATED
NCT02530320 Oligodendroglioma, Oligoastrocytoma Safety and Efficacy of PD0332991 (Palbociclib), a Cyclin-dependent Kinase 4 and 6 Inhibitor, in Patients With Oligodendroglioma or Recurrent Oligoastrocytoma Anaplastic With the Activity of the Protein RB Preserved PHASE2 COMPLETED
NCT03356223 Head and Neck Cancer, Advanced Cancer, Metastatic Cancer Evaluation of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6 PHASE2 COMPLETED
NCT03439046 Breast Cancer Study of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant PHASE3 COMPLETED
NCT06390839 Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm Testing Palbociclib (PD-0332991) as Potentially Targeting Treatment in Cancers With CDK4 or CDK6 Amplification (MATCH - Subprotocol Z1C) PHASE2 ACTIVE_NOT_RECRUITING
NCT01958021 Advanced, Metastatic Breast Cancer Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer PHASE3 COMPLETED