CDKN2B cyclin dependent kinase inhibitor 2B [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDKN2Bprovided by HGNC
Official Full Name: cyclin dependent kinase inhibitor 2Bprovided by HGNC
Primary source: HGNC:HGNC:1788
See related: Ensembl:ENSG00000147883 MIM:600431; AllianceGenome:HGNC:1788
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: P15; MTS2; TP15; CDK4I; INK4B; p15INK4b
Summary: This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]
Expression: Broad expression in colon (RPKM 20.3), small intestine (RPKM 17.6) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p21.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (22002903..22009313, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (22017276..22023690, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (22002902..22009312, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization.
Title: CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization.
Evaluation of rs10811661 polymorphism in CDKN2A / B in colon and gastric cancer.
Title: Evaluation of rs10811661 polymorphism in CDKN2A / B in colon and gastric cancer.
TP53 or CDKN2A/B covariation in ALK/RET/ROS1-rearranged NSCLC is associated with a high TMB, tumor immunosuppressive microenvironment and poor prognosis.
Title: TP53 or CDKN2A/B covariation in ALK/RET/ROS1-rearranged NSCLC is associated with a high TMB, tumor immunosuppressive microenvironment and poor prognosis.
Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.
Title: Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.
Loss of CDKN2A/B is a Molecular Marker of High-grade Histology and is Associated with Aggressive Behavior in Acinic Cell Carcinoma.
Title: Loss of CDKN2A/B is a Molecular Marker of High-grade Histology and is Associated with Aggressive Behavior in Acinic Cell Carcinoma.
Association of CDKN2A/B mutations, PD-1, and PD-L1 with the risk of acute lymphoblastic leukemia in children.
Title: Association of CDKN2A/B mutations, PD-1, and PD-L1 with the risk of acute lymphoblastic leukemia in children.
KIT A502_Y503 duplication mutation serves as a potential and universal target for neoantigen peptide in Chinese GIST patients.
Title: KIT A502_Y503 duplication mutation serves as a potential and universal target for neoantigen peptide in Chinese GIST patients.
Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer.
Title: Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer.
Translational significance of CDKN2A/B homozygous deletion in isocitrate dehydrogenase-mutant astrocytoma.
Title: Translational significance of CDKN2A/B homozygous deletion in isocitrate dehydrogenase-mutant astrocytoma.
PRMT6 functionally associates with PRMT5 to promote colorectal cancer progression through epigenetically repressing the expression of CDKN2B and CCNG1.
Title: PRMT6 functionally associates with PRMT5 to promote colorectal cancer progression through epigenetically repressing the expression of CDKN2B and CCNG1.

Submit: New GeneRIF Correction See all GeneRIFs (304)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
1000 Genomes-based imputation identifies novel and refined associations for the Wellcome Trust Case Control Consortium phase 1 Data. EBI GWAS Catalog EBI GWAS CatalogPubMed
A common variant on chromosome 9p21 affects the risk of myocardial infarction. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of optic disc parameters. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. EBI GWAS Catalog EBI GWAS CatalogPubMed
Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data. EBI GWAS Catalog EBI GWAS CatalogPubMed
Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Chromosome 7p11.2 (EGFR) variation influences glioma risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association meta-analysis identifies new endometriosis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies five new breast cancer susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies five susceptibility loci for glioma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies three novel loci for type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of coronary and aortic calcification implicates risk loci for coronary artery disease and myocardial infarction. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of coronary artery disease in the Japanese. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of intracranial aneurysm identifies three new risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Susceptibility loci for intracranial aneurysm in European and Japanese populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Two-marker association tests yield new disease associations for coronary artery disease and hypertension. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D9S958 (e-PCR)
- UniSTS:150060

PMC108944P1 (e-PCR)
- UniSTS:270146

STS-N34320 (e-PCR)
- UniSTS:40275

GDB:679533 (e-PCR)
- UniSTS:158609

GDB:679534 (e-PCR)
- UniSTS:158610

D9S1605 (e-PCR)
- UniSTS:153237

GDB:626109 (e-PCR)
- UniSTS:158392

D9S1752 (e-PCR)
- UniSTS:154086

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
involved_in cellular response to extracellular stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to nutrient	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to transforming growth factor beta stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in megakaryocyte differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of glial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of G0 to G1 transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of G1/S transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in response to cytokine	IEA Inferred from Electronic Annotation more info
involved_in response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in spleen development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cyclin-dependent kinase 4 inhibitor B

Names: CDK inhibitory protein; CDK4B inhibitor; MTS-2; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4); cyclin-dependent kinases 4 and 6 binding protein; multiple tumor suppressor 2; p14-INK4b; p14_CDK inhibitor; p14_INK4B; p15 CDK inhibitor; p15-INK4b; p15_INK4B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023297.1 RefSeqGene

Range

5009..11411

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004936.4 → NP_004927.2 cyclin-dependent kinase 4 inhibitor B isoform 1

See identical proteins and their annotated locations for NP_004927.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AF488731, BC014469, BC018984, BI560960

Consensus CDS

CCDS6512.1

UniProtKB/Swiss-Prot

O15125, P42772, Q6FI09

UniProtKB/TrEMBL

K7PPU3

Related

ENSP00000276925.6, ENST00000276925.7

Conserved Domains (2) summary

cd00204
Location:21 → 132

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:46 → 76

ANK; ANK repeat [structural motif]
NM_078487.2 → NP_511042.1 cyclin-dependent kinase 4 inhibitor B isoform 2

See identical proteins and their annotated locations for NP_511042.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses a different splice site, which leads to a translation frame shift, when compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct C-terminus when compared to isoform 1.

Source sequence(s)

AF004819, AF488731, BC014469, BC018984, BI560960

Consensus CDS

CCDS6513.1

UniProtKB/TrEMBL

Q5ZEY8

Related

ENSP00000369487.4, ENST00000380142.5

Conserved Domains (1) summary

cl02529
Location:21 → 54

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...