Human Gene CDKN2A (uc010miu.3)
Description: Homo sapiens cyclin-dependent kinase inhibitor 2A (CDKN2A), transcript variant 5, mRNA.
RefSeq Summary (NM_001195132): 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].
Transcript (Including UTRs)
Position: hg19 chr9:21,967,751-21,975,132 Size: 7,382 Total Exon Count: 4 Strand: -
Coding Region
Position: hg19 chr9:21,968,724-21,974,826 Size: 6,103 Coding Exon Count: 3
Data last updated at UCSC: 2013-06-14
Sequence and Links to Tools and Databases
Primer design for this transcript
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): CDKN2A
CDC HuGE Published Literature: CDKN2A
Positive Disease Associations: adult T-cell leukemia
, Basophils
, bladder cancer
, breast cancer melanoma
, Coronary Artery Disease|Hypertension|Myocardial Infarction|Stroke
, coronary disease
, Coronary Heart Disease
, Diabetes mellitus type II|Diabetes Mellitus, Type 2|Glucose Metabolism Disorders
, diabetes, type 2
, esophageal squamous cell carcinoma
, familial melanoma
, glioma
, intracranial aneurysm
, lung carcinoma
, melanoma
, myocardial infarct
, myocardial infarction
, myocardial infarction (early onset)
, neurofibromatosis 1
, non-small cell lung carcinoma
, oligodendrogliomas
, ovarian cancer
, overall effect
, pancreatic cancer
, physical function
, Platelet Count
, Posttransplantation diabetes mellitus (PTDM)
, type 2 diabetes
Related Studies: adult T-cell leukemia Fujiwara H et al. 1999, Alteration of p16 (CDKN2) gene is associated with interleukin-2-induced tumor cell growth in adult T-cell leukemia., Experimental hematology. 1999 Jun;27(6):1004-9.
[PubMed 10378889 ]
Basophils , , .
[PubMed 0 ]
bladder cancer Sakano, S. et al. 2003, Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene., International journal of cancer. Journal international du cancer. 2003 Mar;104(1):98-103.
[PubMed 12532425 ]
Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness.
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MalaCards Disease Associations
MalaCards Gene Search: CDKN2A
Diseases sorted by gene-association score: pancreatic cancer/melanoma syndrome * (1325), melanoma and neural system tumor syndrome * (1025), melanoma, cutaneous malignant, 2 * (906), dysplastic nevus syndrome * (818), malignant melanoma, somatic * (402), leukemia, acute lymphoblastic 3 * (164), cdkn2a-related cutaneous malignant melanoma * (125), precursor t-cell acute lymphoblastic leukemia * (90), skin melanoma (49), pancreatic cancer * (32), cervical squamous cell carcinoma (31), cervical adenocarcinoma (31), cervical intraepithelial neoplasia (28), melanoma (27), oropharynx cancer (26), astrocytoma (25), endocervical adenocarcinoma (25), papilloma (24), adenocarcinoma in situ (23), anal squamous cell carcinoma (23), gallbladder adenoma (22), bowenoid papulosis (18), lung cancer (18), localized osteosarcoma (17), uveal melanoma (17), cervical cancer, somatic (17), squamous cell carcinoma (16), endocervical carcinoma (16), vulva squamous cell carcinoma (16), vulva cancer (16), oligodendroglioma (16), endometrial mucinous adenocarcinoma (15), conjunctival intraepithelial neoplasm (15), pleomorphic liposarcoma (15), endometrial transitional cell carcinoma (15), fallopian tube squamous cell carcinoma (15), penile cancer (14), lung carcinoma in situ (14), early invasive cervical adenocarcinoma (14), verrucous carcinoma (14), actinic keratosis (13), primary cutaneous diffuse large b-cell lymphoma, leg type (13), peritoneal mesothelioma (13), glioblastoma multiforme (12), li-fraumeni syndrome (12), megaesophagus (12), malignant peripheral nerve sheath tumor (12), anus cancer (12), atypical lipomatous tumor (12), malignant glioma (11), oral cancer (11), acral lentiginous melanoma (11), adenocarcinoma (11), tonsil cancer (11), pancreatic ductal adenocarcinoma (11), sarcomatoid mesothelioma (11), squamous cell carcinoma, head and neck (11), endometrial cancer (11), keratinizing squamous cell carcinoma (11), fibrosarcoma of bone (11), endometrial adenocarcinoma (10), biliary tract neoplasm (10), malignant peritoneal mesothelioma (10), basaloid squamous cell carcinoma (10), urinary bladder cancer (10), ameloblastic carcinoma (10), brain stem astrocytic neoplasm (10), barrett's adenocarcinoma (10), scrotal carcinoma (10), esophageal cancer (10), persistent hyperplastic primary vitreous (10), ocular melanoma (10), breast papillomatosis (10), oral squamous cell carcinoma (10), larynx cancer (10), inverted papilloma (10), fallopian tube endometrioid adenocarcinoma (10), cholangiolocellular carcinoma (10), small cell neuroendocrine carcinoma (10), bladder cancer, somatic (10), vulvar seborrheic keratosis (9), mesothelioma, somatic (9), nasopharyngeal carcinoma (9), cervix uteri carcinoma in situ (9), anal canal carcinoma (9), gallbladder cancer (9), pharynx cancer (9), bladder squamous cell carcinoma (9), cd3epsilon deficiency (9), barrett esophagus/esophageal adenocarcinoma (9), central nervous system lymphoma (8), bladder carcinoma in situ (8), dedifferentiated liposarcoma (8), acute lymphoblastic leukemia, childhood (8), vulval paget's disease (8), grade iii astrocytoma (8), blastic plasmacytoid dendritic cell (8), inverted transitional papilloma (8), spitz nevus (8), mucinous bronchioloalveolar adenocarcinoma (8), tonsil squamous cell carcinoma (8), cell type cancer (8), tongue squamous cell carcinoma (8), vulvar dystrophy (8), cervix disease (8), neurofibroma (8), leukemia (8), retinoblastoma (7), nasal cavity cancer (7), anaplastic oligodendroglioma (7), mucinous adenocarcinoma (7), atypical neurofibroma (7), vulva adenocarcinoma (7), retinal cancer (7), tongue cancer (7), sensory system cancer (7), primary central nervous system lymphoma (7), acute lymphocytic leukemia (7), oral leukoplakia (7), bizarre leiomyoma (7), pancreatic ductal carcinoma (7), adenoid basal cell carcinoma (7), adult t-cell leukemia (7), pilocytic astrocytoma (7), thyroid lymphoma (6), malignant pleural mesothelioma (6), liposarcoma (6), nasal cavity adenocarcinoma (6), infiltrating angiolipoma (6), integumentary system cancer (6), melanomatosis (6), gastric adenosquamous carcinoma (6), retroperitoneum carcinoma (6), retinitis pigmentosa 22 (6), skin carcinoma in situ (6), cholecystitis (6), plasmablastic lymphoma (6), pleural cancer (6), pre-malignant neoplasm (6), balanitis xerotica obliterans (6), balanoposthitis (6), bone squamous cell carcinoma (6), leukemia, acute lymphoblastic (6), anogenital venereal wart (6), chordoma (6), chronic cervicitis (6), ductal carcinoma in situ (6), epstein-barr virus-associated gastric carcinoma (5), cervicitis (5), lymphoblastic leukemia (5), glioblastoma (5), glioma (5), histiocytic sarcoma (5), esophagus adenocarcinoma (5), lynch syndrome (5), keratosis (5), vulvar intraepithelial neoplasia (5), ewing's family of tumors (5), ocular cancer (5), female reproductive organ cancer (5), chromosome 2p16.1-p15 deletion syndrome (5), optic nerve sheath meningioma (5), blackwater fever (5), endometrial squamous cell carcinoma (5), conventional leiomyosarcoma (5), chondromyxoid fibroma (5), cervix small cell carcinoma (5), pancreas adenocarcinoma (5), ischemic fasciitis (5), colorectal cancer (5), cervical adenosquamous carcinoma (5), nervous system cancer (5), bone cancer (5), anal canal squamous cell carcinoma (5), glycogen-rich clear cell breast carcinoma (5), acute kidney tubular necrosis (5), colon lymphoma (4), periosteal chondrosarcoma (4), central nervous system melanocytic neoplasm (4), in situ carcinoma (4), vulvar melanoma (4), meningeal melanocytoma (4), breast giant fibroadenoma (4), nasal cavity squamous cell carcinoma (4), meningeal melanomatosis (4), cellular schwannoma (4), juvenile pilocytic astrocytoma (4), necrotizing sialometaplasia (4), optic nerve neoplasm (4), b-cell lymphomas (4), nodular malignant melanoma (3), hepatocellular carcinoma (3), mantle cell lymphoma (3), kidney cancer (3), gastrointestinal stromal tumor (3), stomach cancer (3), lung cancer susceptibility 3 (2), multiple myeloma (2), osteosarcoma, somatic (2), adamantinoma of long bones (2), ovarian cancer, somatic (2), gastrointestinal system cancer (2), reproductive organ cancer (2), cell type benign neoplasm (1), endocrine gland cancer (1), gastrointestinal system benign neoplasm (1), tetralogy of fallot (1), gastric cancer, somatic (1), leukemia, acute myeloid (0)* = Manually curated disease association
Comparative Toxicogenomics Database (CTD)
Common Gene Haplotype Alleles
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RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
Microarray Expression Data
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mRNA Secondary Structure of 3' and 5' UTRs
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Protein Domain and Structure Information
SCOP Domains: 48403 - Ankyrin repeat
ModBase Predicted Comparative 3D Structure on P42771-4
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Descriptions from all associated GenBank mRNAs
KC806059 - Homo sapiens p14ARF/p16INK4a fusion protein (p14ARF/p16INK4a fusion) mRNA, complete cds.KC814157 - Homo sapiens p16-ACT fusion protein (p16ink4a) mRNA, complete cds.L27211 - Human CDK4-inhibitor (p16-INK4) mRNA, complete cds.U26727 - Human p16INK4/MTS1 mRNA, complete cds.JD507893 - Sequence 488917 from Patent EP1572962.BC015960 - Homo sapiens cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4), mRNA (cDNA clone IMAGE:3954155), partial cds.BC021998 - Homo sapiens cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4), mRNA (cDNA clone IMAGE:2988668), partial cds.U38945 - Human hypothetical 18.1 kDa protein (CDKN2A) mRNA, complete cds.KF311101 - Homo sapiens CAI2 lncRNA (CDKN2A), partial sequence.JQ694043 - Homo sapiens isolate iPCH460_Col5 cyclin-dependent kinase inhibitor 2A (CDKN2A) mRNA, complete cds.JQ694044 - Homo sapiens isolate iPCH460_Col9 cyclin-dependent kinase inhibitor 2A (CDKN2A) mRNA, complete cds.JQ694045 - Homo sapiens isolate iPCH460_Col12 cyclin-dependent kinase inhibitor 2A (CDKN2A) mRNA, complete cds.DQ318021 - Homo sapiens cyclin-dependent kinase inhibitor (CDKN2A) mRNA, complete cds, alternatively spliced.JD189027 - Sequence 170051 from Patent EP1572962.AF115544 - Homo sapiens cyclin-dependent kinase inhibitor p12 (p16INK4a) mRNA, alternatively spliced form, complete cds.JD435944 - Sequence 416968 from Patent EP1572962.JD037742 - Sequence 18766 from Patent EP1572962.JD391771 - Sequence 372795 from Patent EP1572962.S78535 - tumor suppressor gene, P16/MTS1/CDKN2=cell cycle negative regulator beta form [human, mRNA Partial, 660 nt].KJ901333 - Synthetic construct Homo sapiens clone ccsbBroadEn_10727 CDKN2A gene, encodes complete protein.JD484377 - Sequence 465401 from Patent EP1572962.JD322858 - Sequence 303882 from Patent EP1572962.BT007020 - Homo sapiens cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) mRNA, complete cds.AB464504 - Synthetic construct DNA, clone: pF1KB8879, Homo sapiens CDKN2A gene for cyclin-dependent kinase inhibitor 2A, without stop codon, in Flexi system.JD157669 - Sequence 138693 from Patent EP1572962.JD400426 - Sequence 381450 from Patent EP1572962.JD200275 - Sequence 181299 from Patent EP1572962.JD333905 - Sequence 314929 from Patent EP1572962.JD333904 - Sequence 314928 from Patent EP1572962.JD068626 - Sequence 49650 from Patent EP1572962.JD538094 - Sequence 519118 from Patent EP1572962.JD200541 - Sequence 181565 from Patent EP1572962.JD141662 - Sequence 122686 from Patent EP1572962.JD067725 - Sequence 48749 from Patent EP1572962.JD370027 - Sequence 351051 from Patent EP1572962.JD520320 - Sequence 501344 from Patent EP1572962.JD485687 - Sequence 466711 from Patent EP1572962.JD196032 - Sequence 177056 from Patent EP1572962.
Biochemical and Signaling Pathways
Other Names for This Gene
Gene Model Information
category:
coding
nonsense-mediated-decay:
yes
RNA accession:
NM_001195132.1
exon count:
4 CDS single in 3' UTR:
no
RNA size:
1464
ORF size:
504 CDS single in intron:
no
Alignment % ID:
100.00
txCdsPredict score:
610.00 frame shift in genome:
no
% Coverage:
99.11
has start codon:
yes
stop codon in genome:
no
# of Alignments:
1
has end codon:
yes
retained intron:
no
# AT/AC introns
0
selenocysteine:
no
end bleed into intron:
0 # strange splices:
0
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Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.