CDKN2A

Tumour Suppressor
Cyclin-dependent kinase inhibitor 2A UniProt accession P42771

Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein

Source: UniProt

Heterodimer with CDK4 or CDK6. Predominant p16 complexes contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity.

Interacts with ISCO2

Source: UniProt
Cytoplasm, Nucleus
Source: UniProt

Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific

Source: UniProt
  • Unknown disease
  • Melanoma, cutaneous malignant 2 (CMM2)

    A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites.

  • Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC)

    An inherited cancer predisposition syndrome characterized by an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer.

  • Melanoma-astrocytoma syndrome (MASTS)

    Characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.

Source: UniProt
  • Oxidative Stress Induced Senescence
  • Senescence-Associated Secretory Phenotype (SASP)
  • Oncogene Induced Senescence
  • Cyclin D associated events in G1
  • Transcriptional Regulation by VENTX
  • Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4
  • 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
  • Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
  • Regulation of MITF-M-dependent genes involved in cell cycle and proliferation
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.19%
Lung Adenocarcinoma 2.44%
Lung Small Cell Carcinoma 0.30%
Lung Squamous Cell Carcinoma 7.62%
Oesophagus Adenocarcinoma 7.12%
Oesophagus Squamous Cell Carcinoma 5.51%
Pancreas Ductal Carcinoma 6.91%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CDKN2A, 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: 94

NCT ID Condition Brief Title Phase Status
NCT02540876 Metastatic Malignant Neoplasm, Solid Neoplasm, Unresectable Malignant Neoplasm Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery PHASE1 COMPLETED
NCT02202200 Melanoma BRAF V600E/K Mutated, CDNKN2A Loss Defined Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma PHASE1, PHASE2 UNKNOWN
NCT07063745 Metastatic Non-small Cell Lung Cancer With MTAP Deletion A Study to Compare the Combination of BMS-986504 With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer Participants With Homozygous MTAP Deletion PHASE2, PHASE3 RECRUITING
NCT02526316 HPV-induced Cancers Cisplatin-based Chemotherapy Combined With P16_37-63 Peptide Vaccination in Patients With HPV-positive Cancers PHASE1 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
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
NCT01810913 Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma, Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7 Testing Docetaxel-Cetuximab or the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy and Radiation Therapy in High-Risk Head and Neck Cancer PHASE2, PHASE3 RECRUITING
NCT06789653 Breast Cancer A Novel Approach Utilizing Organ Specific Age Proteomics N/A RECRUITING
NCT06509997 Head and Neck Squamous Cell Carcinoma A Phase II Study of Anti-EGFR Antibody-drug Conjugate (ADC) Combine With CDK4/6 Inhibitors Posterior Line in the Treatment of Recurrent/Metastatic CDKN2A Gene Variant Head and Neck Squamous Cell Carcinoma PHASE2 NOT_YET_RECRUITING
NCT07492680 Solid Tumors A Study of BMS-986504 Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5) PHASE2 NOT_YET_RECRUITING