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CDKN2B (cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4))

Written2011-01Joanna Fares, Linda Wolff, Juraj Bies
Lab Cell Oncology, National Cancer Institute NIH, 37 Convent Dr, Bethesda MD 20892, USA (JF, LW, JB); Biochemistry, Molecular Biology Department, Georgetown University, Washington DC 20037, USA (JF)

(Note : for Links provided by Atlas : click)


HGNC Alias symbP15
HGNC Previous namecyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
LocusID (NCBI) 1030
Atlas_Id 187
Location 9p21.3  [Link to chromosome band 9p21]
Location_base_pair Starts at 22002903 and ends at 22009313 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CDKN2B.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CDKN2A (9p21.3)::CDKN2B (9p21.3)CDKN2B (9p21.3)::DGKD (2q37.1)MTAP (9p21.3)::CDKN2B (9p21.3)


  Figure 1.
Description The p15INK4B gene encompasses 6.41 Kb of DNA and has 2 coding exons. It is tandemly linked to p16INK4A and p14ARF within 42 Kb of genomic locus located on chromosome 9p21. The locus is commonly referred to as INK4/ARF locus.
Transcription CDKN2B gene encodes 2 distinct transcript variants: p15 and p10. p10 arises from an alternative 5' splice donor site within intron 1 of p15.
p15: 3.82 Kb of mRNA.
p10: 0.86 Kb of mRNA.

Regulation: A conserved DNA element with the ability to regulate the entire INK4/ARF locus has been identified in close proximity of the locus and named regulatory domain (RD). It appears to promote transcriptional repression of all three genes encoded by the locus, in a manner dependent on CDC6. In proliferating embryonic fibroblasts (MEFs), EZH2 a member of the polycomb repressive complex 2 (PRC2) as well as BMI1 and M33 members of the polycomb repressive complex 1 (PRC1) are strongly expressed and are found to localize to the INK4/ARF RD. BMI1 has been shown to interact specifically with CDC6. These polycomb group (PcG) complexes repress the locus activity through the establishment of repressive chromatin modifications such as H3K27 trimethylation. During senescence, binding of these complexes to RD is lost and correlates with increased expression of the INK4/ARF genes (Figure 1).
The p15INK4B gene is also silenced by a long non coding RNA, called antisense non-coding RNA in the INK4 locus (ANRIL), whose expression was found to be inversed to the expression of p15INK4B in leukemia cell lines. It was shown that ANRIL induces the silencing of p15INK4B in cis and trans by triggering heterochromatin formation in a Dicer-independent manner. PcG complexes are recruited to the INK4/ARF locus by ANRIL and modulate its repression (Figure 1). Additionally, a naturally occurring antisense circular ANRIL RNAs (cANRIL) has also been described. Different forms of cANRIL are produced in most INK4/ARF expressing cells, suggesting that alternative splicing events leading to different ANRIL structures can contribute to changes in PcG-mediated INK4/ARF repression.
Specific transcription regulators of p15INK4B have also been reported (see Figure 2). These include TGF-b, MIZ-1, SMAD3/SMAD4 complex, SP1, c-MYC, IRF8, PU.1, SNAIL and EGR1 factors among others.
p15INK4B expression is dramatically induced by TGF-b, suggesting that it is a potent downstream effector of TGF-b mediated growth arrest.
MIZ-1 is a transcription factor that has been shown to bind the initiator element (Inr) in the promoter region and induce the transcription of p15INK4B in epithelial cells. However it can also recruit transcriptional co-repressors such as c-MYC and GFI-1 to the promoter region by binding to them and forming inhibitory complexes. TGF-b has been reported to re-activate the core promoter through downregulation of C-MYC and GFI-1, thereby releasing endogenous MIZ-1 from inhibition.
The SMAD3/4 complex readily forms following TGF-b treatment and physical interaction between this complex, MIZ-1 and promoter-bound SP1 protein has been described. These interactions have been proposed to constitute a platform for the recruitment of co-activators, and do not seem to be affected by the suppressor activity of c-MYC. The inhibitory function of c-MYC seems to be cell-type dependent, as it was confirmed in epithelial cells but not in the hematopoietic lineage. In myeloid cells, the transcription factor c-MYB was shown to prevent the transcription and the upregulation of p15INK4B which is normally associated with the differentiation process. The mechanism by which C-MYB does this is unclear but it is not through upregulation of c-MYC, a known target of c-MYB.
A tri-component transcriptional complex consisting of SNAIL, SP1 and EGR-1 was also described for its ability to trigger the p15INK4b promoter activation upon TPA treatment.
In murine myeloid cells specifically, the interferon consensus sequence-binding protein/interferon regulatory factor 8 (ICSBP/IRF-8) in combination with PU.1 were shown to bind p15Ink4b promoter and activate the transcription of the gene in response to IFN-b treatment.
In AML patients with , p15INK4B silencing was found to be caused by inv(16)-encoded core binding factor beta-smooth muscle myosin heavy chain (CBFb-SMMHC). CBFb-SMMHC was shown to displace RUNX1 from a newly determined CBF site in the promoter of p15INK4B.


  Figure 2.
Description p15INK4B transcript encodes two protein isoforms p15 and p15.5 that are functionally indistinguishable. p15.5 is an N-terminally extended variant of p15 initiated from an upstream alternative in frame initiation codon. p15 protein is 138 aa long and its mass is 14.72 KDa.
p10 transcript encodes the shorter variant. The protein consists of 78 aa only and its mass is 10 KDa. It shares a similar NH2 terminus to p15 but contains a different basic COOH terminus that is translated from the p15Ink4b intronic region (Figure 2).
Expression p15INK4B is expressed at very low levels under normal physiological conditions. Its expression seems to be lineage restricted. In bone marrow cells the highest level of p15INK4B is mainly detected in maturing monocytes/macrophages and lymphocytes. The gene expression has also been reported to be normally up-regulated during megakaryocytic differentiation. Increased expression of p15INK4B is also detected during stress and senescence of cells.
Localisation Nucleus and cytoplasm.
Function I- Function in the cell cycle. p15INK4B belongs to the INK4 family of protein kinase inhibitors named for their high and exclusive specificity towards the catalytic activity of cyclin dependent kinases 4 (CDK4) or 6 (CDK6). Structural studies have demonstrated that the protein performs its inhibitory activity by allosteric competition with the D-type cyclins to bind CDK4/6 kinases and prevents the formation of active CDK4/6-cyclin-Ds complexes. This keeps the retinoblastoma protein (RB), which is downstream of this pathway, in its hypophosphorylated state. Hypophosporylated RB binds and inactivates the E2F transcription factors required for the transcriptional activation of genes necessary for entry into the S phase of the cell cycle and DNA synthesis.
Three other members of the INK4 family of CDK inhibitors: p16INK4A, p18INK4C and p19INK4D are encoded by unique genes and share roughly 40% homology. They have similar protein structure characterized by the presence of four ankyrin-like motif tandem repeats that are predicted to be engaged in protein-protein interactions.
II- Function during hematopoietic cell differentiation. Another role for p15INK4B during differentiation of early hematopoietic progenitors has also been described. In knockout mice, loss of p15INK4B was shown to favor the differentiation of common myeloid progenitors (CMP) into granulocyte macrophage progenitors (GMP) resulting in an imbalance between the myeloid and the erythroid compartments.
III- Function during cellular senescence. Cellular senescence is accompanied by hallmark features that include the up-regulation of cell cycle inhibitors like p15INK4B, p16INK4A and p21CIP. When overexpressed, p15INK4B engages the RB pathway to promote a stable senescent state which has been shown to occur in part through a process that involves alterations in heterochromatin and the stable silencing of E2F target genes.
Another mechanism that has been described is the inactivation of c-MYC which results in the induction of p15INK4B expression and correlates with the global changes in heterochromatin structure known to be associated with cellular senescence.
Homology p15INK4B is highly conserved. Its sequence in homo sapiens is > 85% similar to bos taurus, mus musculus and rattus norvegicus; and > 70% similar to gallus gallus.


Note Intragenic p15INK4B mutations are highly infrequent.

Implicated in

Entity Various hematological disorders and malignancies
Note p15INK4B is frequently epigenetically silenced in leukemias, myelodysplastic syndromes and myeloproliferative diseases by mechanisms involving aberrant DNA methylation and/or histone modifications. These diseases are subcategorized by the French-American-British (FAB) co-operative group, based on the percentage of blast cells in bone marrow and peripheral blood, degree of cytopenia, and in accordance to the direction of differentiation along the myeloid or lymphoid lineages as well as the degree of maturation of the hematopoietic cells.
Entity Myelodysplastic syndromes (MDS)
Disease Myelodysplastic syndromes are heterogeneous clonal hematologic disorders characterized by dysplasia of the myeloid bone marrow cells accompanied with peripheral blood cytopenia and increased risk of transformation to acute myeloid leukemia (AML). MDS transforms into AML once the percentage of blasts in the bone marrow has exceeded 30% (FAB). MDS can arise in patients de novo (primary MDS), or following chemotherapy or exposure to toxins (secondary MDS). According to the Leukemia and Lymphoma Society reports, MDS most commonly affects males aged 70 and above, and is considered to be a disease of the elderly. About 11000 new cases are diagnosed each year, resulting in an incidence rate of 4 cases per 100000 population for both genders.
Prognosis p15INK4B is silenced by promoter hypermethylation in > 50% of MDS cases. Levels of p15INK4B methylation increase as the disease progresses and provide a marker that can predict occurrence of AML.
Entity Chronic myelomonocytic leukemia (CMML)
Disease The defining features of CMML are an absolute monocytosis in peripheral blood ( > 1x109/L), increased numbers of monocytes in bone marrow, a variable degree of dysplasia and less than 5% and 20% of blasts in peripheral blood and bone marrow, respectively. There are two types of CMML: proliferative and dysplastic. Roughly half of CMML diagnosed patients have an elevated white blood cell count commonly associated with hepatomegaly and splenomegaly (myeloproliferative form of the disease). Patients lacking these features are generally considered to have the myelodysplastic form of the disease.
Prognosis Hypermethylation is found in up to 60% of CMML cases and correlates with a more aggressive form of disease. Experimentally, a LysMCre mouse model was developed in which p15INK4B gene is deleted specifically in cells of the myeloid lineage, to better mimic the loss of the gene expression the way it is observed in humans. The mice develop non-reactive monocytosis of the peripheral blood as well as increased myeloid blast progenitors in the bone marrow. In this way the mice develop symptoms that closely resemble CMML in human patients.
Entity Acute myeloid leukemia (AML)
Disease AML is the most common type of leukemia among adults with 14000 new cases diagnosed each year, and with 9000 deaths per year in the United States. AML classification into ten different subtypes was originally defined by the FAB cooperative group according to the direction of differentiation along the different myeloid lineages as well as the degree of maturation of the cells. However, AML exemplifies a genetically heterogeneous cancer with more than a hundred genetic aberrations implicated in the disease.
Prognosis Despite the great genetic and phenotypic heterogeneity of AML, hypermethylation of the p15INK4B promoter region (CpG island) is found to occur in up to 80% of AML cases across all FAB subtypes. It correlates with a loss of p15INK4B expression, poor prognosis and shorter survival time in patients. The p15INK4B methylation status in AML patients in clinical remission is now monitored and used as a reliable prognostic marker for relapse. These findings were further experimentally confirmed in a conditional knockout mouse model where myeloid-specific gene inactivation resulted in an increased susceptibility to retrovirus-induced myeloid leukemia.
Entity Acute lymphoblastic leukemia (ALL)
Disease There are about 4000 new cases of ALL in the United States each year. It appears most often in children younger than age 10. ALL is the most common leukemia in children. However, it can appear in people of any age. About one-third of cases are adults.
Prognosis In B and T acute lymphoblastic leukemia the p15INK4B promoter methylation as well as deletion of the entire locus has been reported.
Entity Chronic leukemia
Disease Chronic leukemia can be subdivided into two subtypes, chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL). CLL is primarily an adult disease; it is very rare in children and young adults. The median age of diagnosis is 72 years, and about 60% of patients are male. In the United States, about 15000 people are diagnosed with CLL each year.
This disease is also commonly referred to as B-cell chronic lymphocytic leukemia (B-CLL).
Prognosis Promoter hypermethylation has been reported in a small subset of B-CLL (11%) at all stages of the disease. In CML, silencing of p15INK4B either by deletion or hypermethylation of its promoter was not found to be a very frequent event.
Entity Glioblastoma multiforme (GBM)
Disease GBM is the most common and very aggressive brain tumor in adults. It involves glial cells and accounts for more than 50% of parenchymal brain tumors approximately 20% of all intracranial tumors. Glioblastoma growth is characterized by a high motility of tumor cells that display broad chemoresistance leading to frequent post-surgical tumor recurrence. It is one of the most dreaded cancer diagnoses due to its poor prognosis and the limited treatment options, with the median survival duration after diagnosis varying from 6 months to 2 years.
Prognosis Homozygous deletion of the p15INK4B/p14ARF/p16INK4A locus on chromosome 9p21.3 is a signature genetic event that drives the pathogenesis of GBM. The deletion of this locus is the most common homozygous deletion present in GBM (> 75% of samples). Specific p15INK4B promoter methylation was also detected in 37% of patients diagnosed with glioblastoma and it correlated with shorter survival.
Entity Hepatocellular carcinoma (HCC)
Disease HCC is a primary malignancy of the liver that mostly arises secondary to hepatitis B or C viral infections. Outcome of the disease is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery, and the cancer is usually deadly within 3 to 6 months.
Prognosis The suppression of the C-MYC oncogene induces cellular senescence in diverse tumor types including hepatocellular carcinoma and correlates with increased p15INK4b expression. In primary HCC, p15INK4B promoter is hypermethylated in about 50% of the cases, and homozygous deletions of both p16INK4A and p15INK4B have been reported in 30% HCC patients and cell lines. This suggests that p15INK4B might be contributing to human hepatocarcinogenesis through a pathway associated with cellular senescence.


Promoter hypermethylation of p15INK4B, HIC1, CDH1, and ER is frequent in myelodysplastic syndrome and predicts poor prognosis in early-stage patients.
Aggerholm A, Holm MS, Guldberg P, Olesen LH, Hokland P.
Eur J Haematol. 2006 Jan;76(1):23-32.
PMID 16343268
Integrating Myc and TGF-beta signalling in cell-cycle control.
Amati B.
Nat Cell Biol. 2001 May;3(5):E112-3.
PMID 11331894
Methylation status of the p15INK4B gene in hematopoietic progenitors and peripheral blood cells in myelodysplastic syndromes.
Aoki E, Uchida T, Ohashi H, Nagai H, Murase T, Ichikawa A, Yamao K, Hotta T, Kinoshita T, Saito H, Murate T.
Leukemia. 2000 Apr;14(4):586-93.
PMID 10764143
Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1.
Basu S, Liu Q, Qiu Y, Dong F.
Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1433-8. Epub 2009 Jan 22.
PMID 19164764
Myeloid-specific inactivation of p15Ink4b results in monocytosis and predisposition to myeloid leukemia.
Bies J, Sramko M, Fares J, Rosu-Myles M, Zhang S, Koller R, Wolff L.
Blood. 2010 Aug 12;116(6):979-87. Epub 2010 May 10.
PMID 20457873
Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk.
Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE.
PLoS Genet. 2010 Dec 2;6(12):e1001233.
PMID 21151960
Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells.
Drexler HG.
Leukemia. 1998 Jun;12(6):845-59. (REVIEW)
PMID 9639410
Translation of p15.5INK4B, an N-terminally extended and fully active form of p15INK4B, is initiated from an upstream GUG codon.
Fuxe J, Raschperger E, Pettersson RF.
Oncogene. 2000 Mar 23;19(13):1724-8.
PMID 10763830
Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b.
Hu CT, Chang TY, Cheng CC, Liu CS, Wu JR, Li MC, Wu WS.
FEBS J. 2010 Mar;277(5):1202-18. Epub 2010 Feb 1.
PMID 20121949
Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors.
Jeffrey PD, Tong L, Pavletich NP.
Genes Dev. 2000 Dec 15;14(24):3115-25.
PMID 11124804
Deletion of p16 and p15 genes in brain tumors.
Jen J, Harper JW, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B.
Cancer Res. 1994 Dec 15;54(24):6353-8.
PMID 7987828
Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene.
Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y.
Oncogene. 2010 Dec 13. [Epub ahead of print]
PMID 21151178
Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis.
Latres E, Malumbres M, Sotillo R, Martin J, Ortega S, Martin-Caballero J, Flores JM, Cordon-Cardo C, Barbacid M.
EMBO J. 2000 Jul 3;19(13):3496-506.
PMID 10880462
Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors.
Malumbres M, Ortega S, Barbacid M.
Biol Chem. 2000 Sep-Oct;381(9-10):827-38. (REVIEW)
PMID 11076015
Methylation-independent silencing of the tumor suppressor INK4b (p15) by CBFbeta-SMMHC in acute myelogenous leukemia with inv(16).
Markus J, Garin MT, Bies J, Galili N, Raza A, Thirman MJ, Le Beau MM, Rowley JD, Liu PP, Wolff L.
Cancer Res. 2007 Feb 1;67(3):992-1000.
PMID 17283131
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.
Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW.
Cell. 2003 Jun 13;113(6):703-16.
PMID 12809602
Hypermethylation of the p15INK4B gene promoter in B-chronic lymphocytic leukemia.
Papageorgiou SG, Lambropoulos S, Pappa V, Economopoulou C, Kontsioti F, Papageorgiou E, Tsirigotis P, Dervenoulas J, Economopoulos T.
Am J Hematol. 2007 Sep;82(9):824-5.
PMID 17546638
An INKlination for epigenetic control of senescence.
Peters G.
Nat Struct Mol Biol. 2008 Nov;15(11):1133-4.
PMID 18985067
Association of low p16INK4a and p15INK4b mRNAs expression with their CpG islands methylation with human hepatocellular carcinogenesis.
Qin Y, Liu JY, Li B, Sun ZL, Sun ZF.
World J Gastroenterol. 2004 May 1;10(9):1276-80.
PMID 15112341
The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells.
Schmidt M, Bies J, Tamura T, Ozato K, Wolff L.
Blood. 2004 Jun 1;103(11):4142-9. Epub 2004 Feb 19.
PMID 14976051
Deregulated c-Myb expression in murine myeloid leukemias prevents the up-regulation of p15(INK4b) normally associated with differentiation.
Schmidt M, Koller R, Haviernik P, Bies J, Maciag K, Wolff L.
Oncogene. 2001 Sep 27;20(43):6205-14.
PMID 11593429
TGFbeta influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b.
Seoane J, Pouponnot C, Staller P, Schader M, Eilers M, Massague J.
Nat Cell Biol. 2001 Apr;3(4):400-8.
PMID 11283614
Conspirators in a capital crime: co-deletion of p18INK4c and p16INK4a/p14ARF/p15INK4b in glioblastoma multiforme.
Solomon DA, Kim JS, Jean W, Waldman T.
Cancer Res. 2008 Nov 1;68(21):8657-60. (REVIEW)
PMID 18974105
Repression of p15INK4b expression by Myc through association with Miz-1.
Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massague J, Hanel F, Eilers M.
Nat Cell Biol. 2001 Apr;3(4):392-9.
PMID 11283613
Expression of p15(ink4b) gene during megakaryocytic differentiation of normal and myelodysplastic hematopoietic progenitors.
Teofili L, Martini M, Di Mario A, Rutella S, Urbano R, Luongo M, Leone G, Larocca LM.
Blood. 2001 Jul 15;98(2):495-7.
PMID 11435325
Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).
Tessema M, Langer F, Dingemann J, Ganser A, Kreipe H, Lehmann U.
Leukemia. 2003 May;17(5):910-8.
PMID 12750705
Cloning and characterization of p10, an alternatively spliced form of p15 cyclin-dependent kinase inhibitor.
Tsubari M, Tiihonen E, Laiho M.
Cancer Res. 1997 Jul 15;57(14):2966-73.
PMID 9230210
Three genes with different functions in transformation are regulated by c-Myb in myeloid cells.
Wolff L, Schmidt M, Koller R, Haviernik P, Watson R, Bies J, Maciag K.
Blood Cells Mol Dis. 2001 Mar-Apr;27(2):483-8.
PMID 11259171
Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation.
Wu CH, van Riggelen J, Yetil A, Fan AC, Bachireddy P, Felsher DW.
Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13028-33. Epub 2007 Jul 30.
PMID 17664422
Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA.
Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, Cui H.
Nature. 2008 Jan 10;451(7175):202-6.
PMID 18185590


This paper should be referenced as such :
Fares, J ; Wolff, L ; Bies, J
CDKN2B (cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(8):652-657.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 12 ]
  9p Rearrangements in ALL
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Chronic Myelomonocytic Leukemia (CMML)
del(5)(q32q33) EBF1::PDGFRB
del(9p) in Acute Lymphoblastic Leukemia
Primary cutaneous DLBCL, leg type
Nasal T cell lymphoma (published in 2008)
Pediatric T-Cell Acute Lymphoblastic Leukemia
Primary Cutaneous B-Cell Lymphomas
t(5;9)(q35;q34) SQSTM1::NUP214
T-lineage acute lymphoblastic leukemia (T-ALL)
Classification of T-Cell disorders

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Familial glioma

External links


HGNC (Hugo)CDKN2B   1788
Atlas Explorer : (Salamanque)CDKN2B
Entrez_Gene (NCBI)CDKN2B    cyclin dependent kinase inhibitor 2B
AliasesCDK4I; INK4B; MTS2; P15; 
TP15; p15INK4b
GeneCards (Weizmann)CDKN2B
Ensembl hg19 (Hinxton)ENSG00000147883 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000147883 [Gene_View]  ENSG00000147883 [Sequence]  chr9:22002903-22009313 [Contig_View]  CDKN2B [Vega]
ICGC DataPortalENSG00000147883
Genatlas (Paris)CDKN2B
SOURCE (Princeton)CDKN2B
Genetics Home Reference (NIH)CDKN2B
Genomic and cartography
GoldenPath hg38 (UCSC)CDKN2B  -     chr9:22002903-22009313 -  9p21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CDKN2B  -     9p21.3   [Description]    (hg19-Feb_2009)
GoldenPathCDKN2B - 9p21.3 [CytoView hg19]  CDKN2B - 9p21.3 [CytoView hg38]
Genome Data Viewer NCBICDKN2B [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF004819 AF488409 AF488410 AF488411 AF488731
RefSeq transcript (Entrez)NM_004936 NM_078487
Consensus coding sequences : CCDS (NCBI)CDKN2B
Gene ExpressionCDKN2B [ NCBI-GEO ]   CDKN2B [ EBI - ARRAY_EXPRESS ]   CDKN2B [ SEEK ]   CDKN2B [ MEM ]
Gene Expression Viewer (FireBrowse)CDKN2B [ Firebrowse - Broad ]
GenevisibleExpression of CDKN2B in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1030
GTEX Portal (Tissue expression)CDKN2B
Human Protein AtlasENSG00000147883-CDKN2B [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP42772   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP42772  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP42772
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)   
Domains : Interpro (EBI)Ankyrin_rpt-contain_dom    Ankyrin_rpt-contain_sf   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CDKN2B
AlphaFold pdb e-kbP42772   
Human Protein Atlas [tissue]ENSG00000147883-CDKN2B [tissue]
Protein Interaction databases
IntAct (EBI)P42772
Ontologies - Pathways
Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  liver development  cyclin-dependent protein serine/threonine kinase inhibitor activity  cyclin-dependent protein serine/threonine kinase inhibitor activity  protein binding  nucleus  cytoplasm  cytosol  cell cycle  negative regulation of cell population proliferation  response to organic cyclic compound  protein kinase binding  megakaryocyte differentiation  positive regulation of transforming growth factor beta receptor signaling pathway  positive regulation of epithelial cell differentiation  cellular response to extracellular stimulus  cellular response to nutrient  response to cytokine  negative regulation of phosphorylation  negative regulation of cyclin-dependent protein serine/threonine kinase activity  spleen development  negative regulation of epithelial cell proliferation  negative regulation of glial cell proliferation  regulation of G0 to G1 transition  cellular response to transforming growth factor beta stimulus  cellular senescence  negative regulation of G1/S transition of mitotic cell cycle  
Ontology : EGO-EBIregulation of cyclin-dependent protein serine/threonine kinase activity  liver development  cyclin-dependent protein serine/threonine kinase inhibitor activity  cyclin-dependent protein serine/threonine kinase inhibitor activity  protein binding  nucleus  cytoplasm  cytosol  cell cycle  negative regulation of cell population proliferation  response to organic cyclic compound  protein kinase binding  megakaryocyte differentiation  positive regulation of transforming growth factor beta receptor signaling pathway  positive regulation of epithelial cell differentiation  cellular response to extracellular stimulus  cellular response to nutrient  response to cytokine  negative regulation of phosphorylation  negative regulation of cyclin-dependent protein serine/threonine kinase activity  spleen development  negative regulation of epithelial cell proliferation  negative regulation of glial cell proliferation  regulation of G0 to G1 transition  cellular response to transforming growth factor beta stimulus  cellular senescence  negative regulation of G1/S transition of mitotic cell cycle  
REACTOMEP42772 [protein]
REACTOME PathwaysR-HSA-69231 [pathway]   
NDEx NetworkCDKN2B
Atlas of Cancer Signalling NetworkCDKN2B
Wikipedia pathwaysCDKN2B
Orthology - Evolution
GeneTree (enSembl)ENSG00000147883
Phylogenetic Trees/Animal Genes : TreeFamCDKN2B
Homologs : HomoloGeneCDKN2B
Homology/Alignments : Family Browser (UCSC)CDKN2B
Gene fusions - Rearrangements
Fusion : MitelmanCDKN2B::DGKD [9p21.3/2q37.1]  
Fusion : FusionHubASAP1--CDKN2B    CDKN2B--ARF    CDKN2B--CDKN2    CDKN2B--CDKN2A    CDKN2B--DGKD    CDKN2B--RPS2    IP6K2--CDKN2B   
Fusion : QuiverCDKN2B
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCDKN2B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CDKN2B
Exome Variant ServerCDKN2B
GNOMAD BrowserENSG00000147883
Varsome BrowserCDKN2B
ACMGCDKN2B variants
Genomic Variants (DGV)CDKN2B [DGVbeta]
DECIPHERCDKN2B [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCDKN2B 
ICGC Data PortalCDKN2B 
TCGA Data PortalCDKN2B 
Broad Tumor PortalCDKN2B
OASIS PortalCDKN2B [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCDKN2B  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DCDKN2B
Mutations and Diseases : HGMDCDKN2B
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)CDKN2B
DoCM (Curated mutations)CDKN2B
CIViC (Clinical Interpretations of Variants in Cancer)CDKN2B
NCG (London)CDKN2B
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Orphanet121    3560   
Genetic Testing Registry CDKN2B
NextProtP42772 [Medical]
Target ValidationCDKN2B
Huge Navigator CDKN2B [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDCDKN2B
Pharm GKB GenePA26321
Clinical trialCDKN2B
DataMed IndexCDKN2B
PubMed455 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Jan 20 14:04:09 CET 2022

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