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CDKN2A Gene

protein-coding   GIFtS: 68
GCID: GC09M021957

Cyclin-Dependent Kinase Inhibitor 2A

(Previous names: cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits...)
(Previous symbols: CDKN2, MLM)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cyclin-Dependent Kinase Inhibitor 2A1 2     P14ARF2
MLM1 2 3 5     P16-INK4A2
CDKN21 2 3     P16INK42
MTS12 3 5     P16INK4A2
Cyclin-Dependent Kinase Inhibitor 2A (Melanoma, P16, Inhibits CDK4)1 2     P192
Cyclin-Dependent Kinase 4 Inhibitor A2 3     P19ARF2
Multiple Tumor Suppressor 12 3     TP162
CDK4I2 3     CDK4 Inhibitor P16-INK42
MTS-12 3     Cell Cycle Negative Regulator Beta2
CMM22 5     p14ARF3
P162 5     p16-INK43
ARF2     p16-INK4a3
INK42     p16INK4A3
INK4A2     p19ARF3
P142     

External Ids:    HGNC: 17871   Entrez Gene: 10292   Ensembl: ENSG000001478897   OMIM: 6001605   UniProtKB: P427713   
UniProtKB: Q8N7263   

Export aliases for CDKN2A gene to outside databases

Previous GC identifers: GC09M022295 GC09M022168


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CDKN2A Gene:
This gene generates several transcript variants which differ in their first exons. At least three alternatively
spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms
known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located
20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that
specifies a protein which is structurally unrelated to the products of the other variants. This ARF product
functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3
ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and
functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the
regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1
control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important
tumor suppressor gene. (provided by RefSeq, Sep 2012)

GeneCards Summary for CDKN2A Gene:
CDKN2A (cyclin-dependent kinase inhibitor 2A) is a protein-coding gene. Diseases associated with CDKN2A include melanoma astrocytoma syndrome, and orolaryngeal cancer, multiple. GO annotations related to this gene include protein kinase binding and p53 binding. An important paralog of this gene is CDKN2C.

UniProtKB/Swiss-Prot: CD2A2_HUMAN, Q8N726
Function: Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and
blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of
MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also
induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2
complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and
blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to
TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA
transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation,
thus inhibiting rRNA processing. Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination.
Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1.
Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and
apoptosis during mammary gland development. Isoform 6 may be involved in regulation of autophagy and
caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP

Gene Wiki entry for CDKN2A (P16) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000009.12  NT_008413.19  NC_018920.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CDKN2A gene promoter:
         AP-1   ATF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CDKN2A promoter sequence
   Search Chromatin IP Primers for CDKN2A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CDKN2A


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9p21   Ensembl cytogenetic band:  9p21.3   HGNC cytogenetic band: 9p21

CDKN2A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CDKN2A gene location

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09M021957:  view genomic region     (about GC identifiers)

Start:
21,967,751 bp from pter      End:
21,995,300 bp from pter
Size:
27,550 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: CD2A1_HUMAN, P42771 (See protein sequence)
Recommended Name: Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3  
Size: 156 amino acids; 16533 Da
Subunit: Heterodimer with CDK4 or CDK6. Predominant p16 complexes contained CDK6. Interacts (isoforms 1,2 and 4)
with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4
kinase activity. Interacts with ISCO2
Sequence caution: Sequence=AAB60645.1; Type=Erroneous initiation;
4 PDB 3D structures from and Proteopedia for CDKN2A:
1A5E (3D)        1BI7 (3D)        1DC2 (3D)        2A5E (3D)    
Secondary accessions: A5X2G7 D3DRK1 O95440 Q15191 Q5VVJ5 Q96B52 Q9NP05
Alternative splicing: 6 isoforms:  P42771-1   P42771-2   P42771-3   Q8N726-1   P42771-4   Q8N726-2   (Barely detectable in non-tumor cells)

UniProtKB/Swiss-Prot: CD2A2_HUMAN, Q8N726 (See protein sequence)

Recommended Name: Cyclin-dependent kinase inhibitor 2A, isoform 4  
Size: 132 amino acids; 13903 Da
Subunit: Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or CDK6. Binds to BCL6, E2F1, HUWE1, MDM2, MYC,
NPM1/B23, TOP1/TOPOI and UBE2I/UBC9. Interacts with TBRG1 and COMMD1. Interacts with CDKN2AIP and E4F1. Isoform 6
interacts with C1QBP
Sequence caution: Sequence=AAB01737.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Sequence=AAC60649.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH15960.3;
Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH21998.3; Type=Erroneous
initiation; Note=Translation N-terminally shortened; Sequence=AAM77919.1; Type=Erroneous initiation;
Note=Translation N-terminally shortened; Sequence=CAH70601.1; Type=Erroneous initiation; Note=Translation
N-terminally shortened; Sequence=EAW58600.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Sequence=EAW58601.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Secondary accessions: D3DRK2 Q13195 Q13399 Q16360 Q7KZR9
Alternative splicing: 6 isoforms:  Q8N726-1   P42771-1   P42771-2   P42771-3   P42771-4   Q8N726-2   (Barely detectable in non-tumor cells)

Explore the universe of human proteins at neXtProt for CDKN2A: NX_Q8N726

Explore proteomics data for CDKN2A at MOPED

Post-translational modifications: 

  • Phosphorylation seems to increase interaction with CDK41
  • Ubiquitinated in normal cells by TRIP12 via the ubiquitin fusion degradation (UFD) pathway, a process that
    mediates ubiquitination at the N-terminus, regardeless of the absence of lysine residues. Ubiquitination leads to
    its degradation. In cancer cells, however, TRIP12 is located in a different cell compartment, preventing
    ubiquitination and degradation1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See CDKN2A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_000068.1  NP_001182061.1  NP_478102.2  NP_478104.2  

    ENSEMBL proteins: 
     ENSP00000307101   ENSP00000462950   ENSP00000464202   ENSP00000467390   ENSP00000432664  
     ENSP00000418915   ENSP00000467857   ENSP00000369496   ENSP00000464952   ENSP00000466887  
     ENSP00000468510   ENSP00000394932   ENSP00000355153  
    Reactome Protein details: Q8N726 P42771

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    CDKN2A Antibody Products:

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    Cloud-Clone Corp. CLIAs for CDKN2A


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR002110 Ankyrin_rpt
     IPR010868 Cyclin_kinase-Inhib_2A
     IPR020683 Ankyrin_rpt-contain_dom

    Graphical View of Domain Structure for InterPro Entry P42771
    Graphical View of Domain Structure for InterPro Entry Q8N726

    ProtoNet protein and cluster: P42771

    UniProtKB/Swiss-Prot: CD2A1_HUMAN, P42771
    Similarity: Belongs to the CDKN2 cyclin-dependent kinase inhibitor family
    Similarity: Contains 4 ANK repeats


    CDKN2A for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CD2A1_HUMAN, P42771
    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

         UniProtKB/Swiss-Prot: CD2A2_HUMAN, Q8N726
    Function: Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and
    blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of
    MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also
    induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2
    complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and
    blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to
    TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA
    transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation,
    thus inhibiting rRNA processing. Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination.
    Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1.
    Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and
    apoptosis during mammary gland development. Isoform 6 may be involved in regulation of autophagy and
    caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP

         Genatlas biochemistry entry for CDKN2A:
    cyclin dependent kinases 4 and 6 (CDK4/CDK6) inhibitor p16 (p16INK4A),blocking them from phosphorylating RB1 and
    preventing exit from G1 phase of the cell cycle, encoding for an alternative reading frame p14ARF,homolog to
    murine p19ARF,putatively inducing G1 and G2 phase arrest,inactivated (LOH) in preneoplastic pancreatic duct
    lesions in head and neck cancer in progression and inactivated by hypermethylation in childhood lymphoblastic
    leukemia (see TSG9A)

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002039p53 binding IPI9529249
    GO:0003677DNA binding IEA--
    GO:0004861cyclin-dependent protein serine/threonine kinase inhibitor activity IDA8259215
    GO:0005515protein binding IPI11278317
    GO:0008134transcription factor binding IPI19057511
         
    CDKN2A for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for CDKN2A:
     Increased apoptosis 

         Selected MGI mutant phenotypes (inferred from 19 alleles(MGI details for Cdkn2a) (see all 21):
     behavior/neurological  cellular  digestive/alimentary  embryogenesis  endocrine/exocrine gland 
     growth/size/body  hematopoietic system  homeostasis/metabolism  immune system  integument 
     liver/biliary system  mortality/aging  muscle  nervous system  no phenotypic analysis 

    CDKN2A for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for CDKN2A: Cdkn2atm2.1Rdp Cdkn2a/Cdkn2bCdkn2a/tm1Brn Cdkn2a/Cdkn2bCdkn2a/tm2Brn Cdkn2atm1Rdp Cdkn2atm1Cjs Cdkn2atm1Nesh
                                                         Cdkn2atm2.1Brn

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CDKN2A
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CDKN2A
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CDKN2A

    miRNA
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    miRTarBase miRNAs that target CDKN2A:
    hsa-mir-192-5p (MIRT026702), hsa-mir-155-5p (MIRT020886), hsa-mir-124-3p (MIRT022931), hsa-mir-455-3p (MIRT037910), hsa-mir-215-5p (MIRT024932), hsa-mir-34a-5p (MIRT025556), hsa-mir-125b-5p (MIRT004709), hsa-mir-16-5p (MIRT031803), hsa-mir-10b-5p (MIRT006368), hsa-mir-320a (MIRT044426), hsa-mir-24-3p (MIRT004362), hsa-let-7g-5p (MIRT004489), hsa-mir-615-3p (MIRT039976), hsa-mir-296-3p (MIRT038476), hsa-mir-423-5p (MIRT038036)

    Block miRNA regulation of human, mouse, rat CDKN2A using miScript Target Protectors
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    SwitchGear 3'UTR luciferase reporter plasmidCDKN2A 3' UTR sequence
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CD2A1_HUMAN, P42771: Cytoplasm. Nucleus
    CD2A2_HUMAN, Q8N726: Nucleus, nucleolus. Nucleus, nucleoplasm
    CD2A2_HUMAN, Q8N726: Isoform 6: Mitochondrion
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    nucleus5
    cytosol4
    extracellular3
    golgi apparatus3
    cytoskeleton2
    endoplasmic reticulum2
    endosome2
    plasma membrane2
    peroxisome1
    vacuole1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA16243918
    GO:0005654nucleoplasm TAS--
    GO:0005730nucleolus IDA--
    GO:0005737cytoplasm IDA16243918
    GO:0005739mitochondrion IEA--

    CDKN2A for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CDKN2A About   (see all 27)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Glioma
    Glioma0.51
    Signaling Pathways in Glioblastoma0.36
    Non-small cell lung cancer0.51
    Bladder cancer0.31
    Melanoma0.43
    2Cyclins and Cell Cycle Regulation
    Cyclins and Cell Cycle Regulation0.67
    G1 Phase0.31
    G1-S Phase Transition0.67
    Cyclin D associated events in G10.31
    3Cell cycle
    Cell cycle0.59
    Cell cycle0.59
    4E2F mediated regulation of DNA replication
    Mitotic G1-G1/S phases0.81
    G1 to S cell cycle control0.35
    5Cellular Senescence
    Cellular Senescence0.81
    Oxidative Stress Induced Senescence0.64
    Cellular responses to stress0.81
    Senescence-Associated Secretory Phenotype (SASP)0.57

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CDKN2A (see all 10)
        Mitochondrial Apoptosis
    Molecular Mechanisms of Cancer
    HIF1Alpha Pathway
    CRHR Pathway
    Glioblastoma Multiforme

    1 Cell Signaling Technology (CST) Pathway for CDKN2A
        Cell Cycle / Checkpoint Control

    2 GeneGo (Thomson Reuters) Pathways for CDKN2A
        Transcription P53 signaling pathway
    Cell cycle Regulation of G1/S transition (part 1)

    Selected BioSystems Pathways for CDKN2A (see all 8)
        Apoptosis
    Cell cycle
    Apoptosis Modulation and Signaling
    Senescence and Autophagy
    G1 to S cell cycle control

    4 Reactome Pathways for CDKN2A
        Oxidative Stress Induced Senescence
    Senescence-Associated Secretory Phenotype (SASP)
    Oncogene Induced Senescence
    Cyclin D associated events in G1


    Selected Kegg Pathways  (Kegg details for CDKN2A) (see all 12):
        Cell cycle
    p53 signaling pathway
    HTLV-I infection
    Pathways in cancer
    Viral carcinogenesis


    CDKN2A for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CDKN2A (see all 16): 
              Lung Cancer in human mouse rat
              Autophagy in human mouse rat
              Prostate Cancer in human mouse rat
              Hypoxia Signaling Pathway in human mouse rat
              Cell Cycle in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CDKN2A

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CDKN2A (Q8N7261, 2, 3 P427711, 2, 3 ENSP000003551534) via UniProtKB, MINT, STRING, and/or I2D (see all 195)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ZNF420Q8TAQ51, 2EBI-8169299,EBI-3923307 MINT-7989705 MINT-7989653 MINT-7989686 MINT-7989603 MINT-7989635 MINT-7989724 MINT-7989747 MINT-7989626
    EGR1P181461, 2, ENSP000002399384EBI-625922,EBI-2834611 MINT-7011792 MINT-7011820 MINT-7011781 MINT-7011806 STRING: ENSP00000239938
    MDM2Q009871, 2, ENSP000004172814EBI-625922,EBI-389668 MINT-7989812 STRING: ENSP00000417281
    MYCNP041981, 2, ENSP000002810434EBI-625922,EBI-878369 MINT-4648228 MINT-4648205 MINT-4648189 STRING: ENSP00000281043
    NPM1P067481, 2, ENSP000002969304EBI-625922,EBI-78579 MINT-3089410 STRING: ENSP00000296930
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 40):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000075cell cycle checkpoint IMP16243918
    GO:0000082G1/S transition of mitotic cell cycle IDA10208428
    GO:0000209protein polyubiquitination IDA18305112
    GO:0000278mitotic cell cycle TAS--
    GO:0001953negative regulation of cell-matrix adhesion IMP10205165

    CDKN2A for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Tocris compounds for CDKN2A (CD2A2)

    Selected Novoseek inferred chemical compound relationships for CDKN2A gene (see all 119)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    5-aza-2'deoxycytidine 76.1 107 19742343 (4), 11589304 (3), 19787243 (3), 7566983 (2) (see all 45)
    5-methylthioadenosine 70.2 29 12796375 (2), 7898924 (2), 8640765 (2), 9426690 (2) (see all 16)
    mtsi 67.9 4 8703847 (1), 7591954 (1), 7542912 (1)
    sodium bisulfite 60.7 10 10706122 (1), 17487400 (1), 15342451 (1), 17369979 (1) (see all 9)
    crcs 57.1 23 17451198 (2), 15492985 (2), 12973852 (2), 14719111 (2) (see all 11)
    o6-methylguanine 54.9 21 16258509 (2), 16203797 (1), 19047896 (1), 14633667 (1) (see all 12)
    paraffin 54.7 48 12479060 (2), 9495360 (1), 9620022 (1), 15328914 (1) (see all 40)
    hpvs 48 8 9846965 (2), 14501820 (1), 14767609 (1), 15608419 (1) (see all 5)
    5-methylcytosine 43.2 5 9808523 (1), 12154064 (1), 11751682 (1)
    fascaplysin 42.8 2 16936279 (1), 15309028 (1)



    CDKN2A for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
    About This Section

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    REFSEQ mRNAs for CDKN2A gene (5 alternative transcripts): 
    NM_000077.4  NM_001195132.1  NM_058195.3  NM_058197.4  NM_058196.1  

    Unigene Cluster for CDKN2A:

    Cyclin-dependent kinase inhibitor 2A
    Hs.512599  [show with all ESTs]
    Unigene Representative Sequence: BQ945397
    17 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000304494(uc003zpj.3 uc010miu.3 uc003zpk.3) ENST00000579755
    ENST00000579122 ENST00000578845 ENST00000530628 ENST00000498124 ENST00000498628
    ENST00000380151 ENST00000494262 ENST00000479692 ENST00000577854 ENST00000380150
    ENST00000497750 ENST00000470819 ENST00000582361 ENST00000446177 ENST00000361570(uc003zpl.3)

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA sequence: 

    AF115544.1 AJ844636.1 BC015960.2 BC021998.2 BT007020.1 DQ318021.1 L27211.1 S78535.1 
    U26727.1 U38945.1 

    13 DOTS entries:

    DT.444664  DT.95191891  DT.95191893  DT.95191887  DT.95191892  DT.91754325  DT.102833213  DT.104796 
    DT.121147160  DT.91754320  DT.91908765  DT.92027925  DT.95191889 

    Selected AceView cDNA sequences (see all 264):

    AI160044 CK904818 AF488410 BM719878 BM831598 NM_078487 N44213 AF488409 
    BF000057 BM126144 CR604976 BM701855 BM475019 BQ441101 BM843979 CB160611 
    BG031050 AU279609 BX502404 BQ002393 CR536529 NM_004936 AF004819 BC014469 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for CDKN2A (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b · 7c ^ 8a · 8b · 8c · 8d
    SP1:                    -     -           -     -     -     -     -     -           -                           
    SP2:                                                        -     -     -           -                           
    SP3:                                                              -     -           -                           
    SP4:                    -     -     -     -     -     -     -     -     -           -                           
    SP5:                    -                                                                                       


    ECgene alternative splicing isoforms for CDKN2A

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CDKN2A expression in normal human tissues (normalized intensities)      CDKN2A embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CCCGCATAGA
    CDKN2A Expression
    About this image


    CDKN2A expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Brain (Nervous System)    fully expand to see all 9 entries
             Thalamus
     
     Epithelial Cells
             Intermediate Keratinocytes Embryonic Epidermis
     
     Epidermis (Integumentary System)    fully expand to see all 3 entries
             Intermediate Keratinocytes Embryonic Epidermis
     
     Bone (Muscoskeletal System)
             HyStem+TGFbeta3+GDF5-induced 7SMOO32 cells
     
     Cartilage (Muscoskeletal System)
             HyStem+TGFbeta3+GDF5-induced 7SMOO32 cells
    CDKN2A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CDKN2A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.512599

    UniProtKB/Swiss-Prot: CD2A1_HUMAN, P42771
    Tissue specificity: Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific


        Pathway & Disease-focused RT2 Profiler PCR Arrays including CDKN2A (see all 16): 
              Lung Cancer in human mouse rat
              Autophagy in human mouse rat
              Prostate Cancer in human mouse rat
              Hypoxia Signaling Pathway in human mouse rat
              Cell Cycle in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for CDKN2A gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cdkn2a1 , 5 cyclin-dependent kinase inhibitor 2A1, 5 75.47(n)1
    74.4(a)1
      4 (42.15 cM)5
    125781  NM_001040654.11  NP_001035744.11 
     892744715 
    chicken
    (Gallus gallus)
    Aves CDKN2B6
    Gallus gallus cyclin-dependent kinase inhibitor 2B...
    57(a)
    1 → many
    Z(78463099-78466508)
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    56(a)
    1 → many
    2(61354501-61364127)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia cdkn2b1 cyclin-dependent kinase inhibitor 2B (p15, inhibits more 56.06(n)
    57.27(a)
      448767  NM_001006919.1  NP_001006920.1 
    zebrafish
    (Danio rerio)
    Actinopterygii LOC1003295281 cyclin-dependent kinase inhibitor 2A-like 52.26(n)
    47.46(a)
      100329528  XM_002660468.2  XP_002660514.1 


    ENSEMBL Gene Tree for CDKN2A (if available)
    TreeFam Gene Tree for CDKN2A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CDKN2A gene
    CDKN2C2  CDKN2B2  CDKN2D2  
    18 SIMAP similar genes for CDKN2A using alignment to 14 protein entries:     CD2A1_HUMAN (see all proteins):
    p16ink4a    CDKN2B    p14ARF    p15    TNKS2    CDKN2C
    TNKS    CDKN2D    ANKRD54    ANKRD53    FPGT-TNNI3K    TNNI3K
    DKFZp434G2126    ESPN    ANK2    ANK3    ANKRD60    KIDINS220

    CDKN2A for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CDKN2A (see all 802)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 9 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs64134641,2,,4
    C,F,HSquamous cell carcinoma4 --21965767(-) ATGTCG/TCACGG 6 A S mis1 ut31 ese313Minor allele frequency- T:0.03MN NS NA WA EU 6527
    rs64134631,2,,4
    C,F,HLeukemia4 --21965777(-) GGCCAT/ACGCGA 6 /Q /H mis1 ut31 ese313Minor allele frequency- A:0.00MN NS EA NA WA 5182
    rs115528221,2,,4
    CMelanoma, cutaneous malignant 2 (CMM2)4 untested121965896(-) TGCACG/TACGCT 7 D Y R L mis1 ut31 ese37Minor allele frequency- T:0.00MN NA 408
    VAR_0014524
    A biliary tract tumor4--see VAR_0014522 E D mis40--------
    VAR_0014484
    Neck and a lung tumor4--see VAR_0014482 D N mis40--------
    VAR_0014874
    Non-small cell lung carcinoma4--see VAR_0014872 G V mis40--------
    VAR_0014274
    Melanoma, cutaneous malignant 2 (CMM2)4--see VAR_0014272 V G mis40--------
    VAR_0585554
    Melanoma, cutaneous malignant 2 (CMM2)4--see VAR_0585552 D Y mis40--------
    VAR_0585514
    Melanoma, cutaneous malignant 2 (CMM2)4--see VAR_0585512 G V mis40--------
    VAR_0014844
    Squamous cell carcinoma4--see VAR_0014842 R C mis40--------

    HapMap Linkage Disequilibrium report for CDKN2A (21967751 - 21995300 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for CDKN2A:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1425040CNV Deletion17803354
    nsv8426CNV Loss18304495
    nsv892746CNV Loss21882294
    nsv892745CNV Gain21882294
    nsv892747CNV Gain21882294

    Human Gene Mutation Database (HGMD): CDKN2A
    Locus Specific Mutation Databases (LSDB): CDKN2A

    Selected Site Specific Mutation Identification with PCR Assays for CDKN2A (see all 19):
    Cosmic IdAA Change
    13604p.A68T
    12481p.W110*
    12504p.H83Y
    12476p.P114L
    12473p.R58*
    Selected Site Specific Cancer Mutation PCR Panels containing CDKN2A (see all 14):
    Esophageal Cancer
    Cancer Comprehensive Panel 384HT
    Tumor Suppressor Panel 384HT
    Gastric Cancer
    Bladder Cancer
    3 Copy Number PCR Panels containing CDKN2A:
    Oncogenes & Tumor Suppressor Genes 384HC
    Breast Cancer
    Lung Cancer
    SeqTarget long-range PCR primers for resequencing CDKN2A
    DNA2.0 Custom Variant and Variant Library Synthesis for CDKN2A

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600160   
    OMIM disorders: 155601  155755  606719  
    UniProtKB/Swiss-Prot: CD2A2_HUMAN, Q8N726
  • Note=The association between cutaneous and uveal melanomas in some families suggests that mutations in
    CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal
    melanoma patients
  • Melanoma, cutaneous malignant 2 (CMM2) [MIM:155601]: A malignant neoplasm of melanocytes, arising de novo
    or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.
    Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
  • Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:606719]: 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. Note=The
    disease is caused by mutations affecting the gene represented in this entry
  • Li-Fraumeni syndrome (LFS) [MIM:151623]: Autosomal dominant familial cancer syndrome that in its classic
    form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative
    affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a
    sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and
    called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of
    malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline
    mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical
    carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15,
    rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric
    cancers. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Melanoma-astrocytoma syndrome (MASTS) [MIM:155755]: Characterized by a dual predisposition to melanoma
    and neural system tumors, commonly astrocytoma. Note=The disease is caused by mutations affecting the gene
    represented in this entry

  • Selected diseases for CDKN2A (see all 332):    About MalaCards
    melanoma astrocytoma syndrome    orolaryngeal cancer, multiple    melanoma, cutaneous malignant, 2    melanoma-pancreatic cancer syndrome
    cdkn2a-related cutaneous malignant melanoma    dysplastic nevus syndrome    anthracosis    atypical mole syndrome
    cervical intraepithelial neoplasia    diffuse large b-cell lymphoma    cutaneous malignant melanoma    primary cutaneous diffuse large b-cell lymphoma, leg type
    cervix uteri carcinoma in situ    ameloblastic carcinoma    blastic plasmacytoid dendritic cell    cd3epsilon deficiency
    endometrial mucinous adenocarcinoma    chromosome 9p deletion    bowenoid papulosis    adenocarcinoma in situ

    Selected diseases from the University of Copenhagen DISEASES database for CDKN2A (see all 25):
    Retinoblastoma     Carcinoma     Melanoma     Oropharynx cancer
    Lung cancer     Cervical cancer     Pancreatic cancer     Malignant glioma
    Wolf-Hirschhorn syndrome     Leukemia     Dysplastic nevus syndrome     Lymphoma
    Colorectal cancer     Urinary bladder cancer     Adenocarcinoma in situ     Kidney failure
    Multiple myeloma     Adenoma     Breast cancer     Skin cancer

    CDKN2A for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for CDKN2A gene (see all 97)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    retinoblastoma 88.2 386 16467168 (10), 11914625 (7), 20039270 (5), 15509364 (4) (see all 99)
    tumors 85.7 3991 9101469 (9), 12149144 (8), 12416540 (7), 19622308 (7) (see all 99)
    melanoma 79.4 1452 16331607 (9), 16234564 (9), 11156381 (8), 17091256 (7) (see all 99)
    carcinoma squamous cell 79 465 12429789 (6), 15328914 (4), 8705996 (4), 9440786 (4) (see all 99)
    microsatellite instability 78.5 51 10194257 (2), 9917133 (2), 12612901 (2), 10411935 (1) (see all 34)
    cancer 77.8 855 12575612 (6), 9464545 (6), 9508208 (5), 15173226 (4) (see all 99)
    familial atypical multiple mole melanoma 76.5 7 7670475 (1), 10956390 (1), 10400925 (1), 18813118 (1) (see all 6)
    allelic loss 76.1 99 8934532 (5), 17659731 (4), 7849711 (3), 11839561 (3) (see all 49)
    multiple tumors 72.9 59 8821952 (2), 7576105 (2), 7473071 (1), 8957063 (1) (see all 38)
    adenocarcinoma 71.8 360 18410530 (6), 15617840 (6), 16496173 (5), 18346352 (5) (see all 99)

    Genetic Association Database (GAD): CDKN2A
    Human Genome Epidemiology (HuGE) Navigator: CDKN2A (284 documents)

    Export disorders for CDKN2A gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CDKN2A gene, integrated from 10 sources (see all 4368):
    (articles sorted by number of sources associating them with CDKN2A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell carcinoma. (PubMed id 19101490)1, 4, 9 Ohta S....Kubota Y. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009)
    2. MC1R variants increase melanoma risk in families with CDKN2A mutations: a meta-analysis. (PubMed id 20189796)1, 4, 9 Fargnoli M.C....Raimondi S. (Eur. J. Cancer 2010)
    3. Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene. (PubMed id 12532425)1, 4, 9 Sakano S....Larsson P. (Int. J. Cancer 2003)
    4. Germline mutations in CDKN2A are infrequent in female patients with melanoma and breast cancer. (PubMed id 19571771)1, 4, 9 Nagore E....GuillAcn C. (Melanoma Res. 2009)
    5. CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. (PubMed id 18983535)1, 4, 9 Pastorino L....Bianchi ScarrA G. (amp 2008)
    6. CDKN2A mutations and melanoma risk in the Icelandic population. (PubMed id 18178632)1, 4, 9 Goldstein A.M....Stefansson K. (J. Med. Genet. 2008)
    7. CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population. (PubMed id 17505264)1, 4, 9 Pjanova D....Heisele O. (Melanoma Res. 2007)
    8. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. (PubMed id 15989956)1, 2, 9 Chen D.... Gu W. (Cell 2005)
    9. Early onset may predict G101W CDKN2A founder mutation carrier status in Ligurian melanoma patients. (PubMed id 15577313)1, 4, 9 Mantelli M....Bianchi-ScarrA G. (Melanoma Res. 2004)
    10. Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma. (PubMed id 12556369)1, 4, 9 Hearle N.... Houlston R.S. (Invest. Ophthalmol. Vis. Sci. 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1029 HGNC: 1787 AceView: CDKN2AandCDKN2B Ensembl:ENSG00000147889 euGenes: HUgn1029
    ECgene: CDKN2A Kegg: 1029 H-InvDB: CDKN2A

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CDKN2A Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CDKN2A Genetics and Cytogenetics in Oncology and Haematology
    CDKN2A Databasehttps://biodesktop.uvm.edu/perl/p16
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=CDKN2A[genesymbol]
    NIEHS-SNPshttp://egp.gs.washington.edu/data/cdkn2a/
    Wikipedia http://en.wikipedia.org/wiki/P16INK4a
    NIEHS-SNPshttp://egp.gs.washington.edu/data/cdkn2a/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CDKN2A gene:
    Search GeneIP for patents involving CDKN2A

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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