Browse CDKN2A

Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus
Domain -
Function

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.

> Gene Ontology
 
Biological Process GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0000082 G1/S transition of mitotic cell cycle
GO:0001558 regulation of cell growth
GO:0001933 negative regulation of protein phosphorylation
GO:0001952 regulation of cell-matrix adhesion
GO:0001953 negative regulation of cell-matrix adhesion
GO:0006323 DNA packaging
GO:0006333 chromatin assembly or disassembly
GO:0006338 chromatin remodeling
GO:0006469 negative regulation of protein kinase activity
GO:0006925 inflammatory cell apoptotic process
GO:0007050 cell cycle arrest
GO:0007160 cell-matrix adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007265 Ras protein signal transduction
GO:0007568 aging
GO:0007569 cell aging
GO:0010657 muscle cell apoptotic process
GO:0010660 regulation of muscle cell apoptotic process
GO:0010661 positive regulation of muscle cell apoptotic process
GO:0010810 regulation of cell-substrate adhesion
GO:0010812 negative regulation of cell-substrate adhesion
GO:0016049 cell growth
GO:0030308 negative regulation of cell growth
GO:0031497 chromatin assembly
GO:0031507 heterochromatin assembly
GO:0031589 cell-substrate adhesion
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0033028 myeloid cell apoptotic process
GO:0033032 regulation of myeloid cell apoptotic process
GO:0033034 positive regulation of myeloid cell apoptotic process
GO:0033673 negative regulation of kinase activity
GO:0034390 smooth muscle cell apoptotic process
GO:0034391 regulation of smooth muscle cell apoptotic process
GO:0034393 positive regulation of smooth muscle cell apoptotic process
GO:0035986 senescence-associated heterochromatin focus assembly
GO:0042326 negative regulation of phosphorylation
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044843 cell cycle G1/S phase transition
GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0045786 negative regulation of cell cycle
GO:0045926 negative regulation of growth
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051348 negative regulation of transferase activity
GO:0070828 heterochromatin organization
GO:0071103 DNA conformation change
GO:0071887 leukocyte apoptotic process
GO:0071888 macrophage apoptotic process
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071901 negative regulation of protein serine/threonine kinase activity
GO:0090342 regulation of cell aging
GO:0090343 positive regulation of cell aging
GO:0090398 cellular senescence
GO:0090399 replicative senescence
GO:1904029 regulation of cyclin-dependent protein kinase activity
GO:1904030 negative regulation of cyclin-dependent protein kinase activity
GO:2000106 regulation of leukocyte apoptotic process
GO:2000108 positive regulation of leukocyte apoptotic process
GO:2000109 regulation of macrophage apoptotic process
GO:2000111 positive regulation of macrophage apoptotic process
GO:2000772 regulation of cellular senescence
GO:2000774 positive regulation of cellular senescence
Molecular Function GO:0004857 enzyme inhibitor activity
GO:0004860 protein kinase inhibitor activity
GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity
GO:0008134 transcription factor binding
GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity
GO:0019207 kinase regulator activity
GO:0019210 kinase inhibitor activity
GO:0019887 protein kinase regulator activity
GO:0030291 protein serine/threonine kinase inhibitor activity
GO:0051059 NF-kappaB binding
Cellular Component GO:0000785 chromatin
GO:0000792 heterochromatin
GO:0035985 senescence-associated heterochromatin focus
> KEGG and Reactome Pathway
 
KEGG hsa04110 Cell cycle
hsa04115 p53 signaling pathway
Reactome R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-69231: Cyclin D associated events in G1
R-HSA-69236: G1 Phase
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-392499: Metabolism of proteins
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-2559585: Oncogene Induced Senescence
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-597592: Post-translational protein modification
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804757: Regulation of TP53 Degradation
R-HSA-6806003: Regulation of TP53 Expression and Degradation
R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins
R-HSA-2990846: SUMOylation
R-HSA-3108214: SUMOylation of DNA damage response and repair proteins
R-HSA-3232118: SUMOylation of transcription factors
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-3700989: Transcriptional Regulation by TP53
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CDKN2A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CDKN2A and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29661773pancreatic ductal adenocarcinomaPromote immunityThree PDAC subtypes were identified: the immune escape (54%), poor in T and B cells and enriched in FOXP3+ regulatory T cells (Treg), with high-grade budding, frequent CDKN2A, SMAD4, and PIK3CA mutations, and poor outcome; the immune rich (35%), rich in T and B cells and poorer in FOXP3+ Tregs, with infrequent budding, lower CDKN2A and PIK3CA mutation rate, and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11 and ATM), and the best outcome; and the immune exhausted (11%), with immunogenic microenvironment and two subpopulations-one with PD-L1 expression and a high PIK3CA mutation rate and a microsatellite-unstable subpopulation with a high prevalence of JAK3 mutations.
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CDKN2A in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 4 Resistant to T-cell proliferation
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CDKN2A in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.4110.666
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)651.1630.642
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.120.945
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9163.1770.0111
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592.4470.191
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 474.1230.0981
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3670.603
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.7660.482
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1030.93
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.210.868
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.9630.58
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682301.2170.00186
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CDKN2A in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141714.3014.30.196
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103200201
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.97.40.51
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.17.71.41
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.27.1-0.91
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDKN2A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDKN2A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDKN2A.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDKN2A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CDKN2A expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CDKN2A and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCDKN2A
Namecyclin-dependent kinase inhibitor 2A
Aliases p16; INK4a; CMM2; ARF; INK4; p16INK4a; p19Arf; p14ARF; cyclin-dependent kinase inhibitor 2A (melanoma, p16, ......
Chromosomal Location9p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CDKN2A collected from DrugBank database.
> Drugs from DrugBank database
 

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