CDKN2B

cyclin dependent kinase inhibitor 2B

Basic information

Region (hg38): 9:22002903-22009305

Links

ENSG00000147883 ∙ NCBI:1030 ∙ OMIM:600431 ∙ HGNC:1788 ∙ Uniprot:P42772 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal cell carcinoma (Moderate), mode of inheritance: AD
• multiple endocrine neoplasia (Limited), mode of inheritance: AD
• glaucoma 1, open angle, E (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDKN2B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDKN2B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			13	2		15
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2	3	5
Total	0	0	14	8	4

Variants in CDKN2B

This is a list of pathogenic ClinVar variants found in the CDKN2B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-22003224-C-A		Malignant tumor of breast	Likely pathogenic (Jul 01, 2023)
9-22003224-C-T		Three Vessel Coronary Disease	Benign (-)
9-22003368-G-A		Three Vessel Coronary Disease • Malignant tumor of breast • Neoplasm	Likely pathogenic; protective (Jul 01, 2023)
9-22004640-G-GA		Malignant tumor of breast	Likely pathogenic (Jul 01, 2023)
9-22005141-T-TTG		Malignant tumor of breast	Likely pathogenic (Jul 01, 2023)
9-22005141-T-TTGTG		Malignant tumor of breast	Likely pathogenic (Jul 01, 2023)
9-22005331-T-G		Three Vessel Coronary Disease	Uncertain significance (-)
9-22005944-G-C		not specified	Likely benign (Aug 15, 2023)
9-22005958-G-T		not specified	Likely benign (Jul 31, 2024)
9-22005996-C-G			Likely benign (Apr 01, 2023)
9-22006003-G-C		not specified	Uncertain significance (Aug 15, 2023)
9-22006018-G-C		not specified	Uncertain significance (Jul 26, 2021)
9-22006037-G-A		not specified	Uncertain significance (Jun 03, 2022)
9-22006044-G-A			Benign (Dec 31, 2019)
9-22006051-T-G		not specified	Uncertain significance (Mar 07, 2024)
9-22006052-CCACGGGCAGACGACCCCAGGCATCGCG-C		not specified	Uncertain significance (Feb 06, 2024)
9-22006061-G-A		not specified	Likely benign (Aug 15, 2023)
9-22006148-C-T		not specified	Conflicting classifications of pathogenicity (Jul 31, 2024)
9-22006152-C-G		not specified	Likely benign (Aug 15, 2023)
9-22006193-CCG-C			Uncertain significance (Jul 04, 2023)
9-22006228-G-A		not specified	Uncertain significance (Apr 24, 2024)
9-22006274-G-T			Benign (Jun 22, 2018)
9-22006349-C-T		Three Vessel Coronary Disease	Benign (Jun 22, 2018)
9-22008505-A-T			Benign (Jun 23, 2018)
9-22008776-G-A		not specified	Likely benign (Aug 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDKN2B	protein_coding	protein_coding	ENST00000276925	2	6461

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00734	0.555	125007	0	12	125019	0.0000480

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.695	112	93.1	1.20	0.00000490	863
Missense in Polyphen		40	33.338	1.1998		320
Synonymous	-0.476	47	43.0	1.09	0.00000236	321
Loss of Function	0.109	3	3.21	0.934	1.41e-7	29

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000884	0.0000797
Middle Eastern	0.00	0.00
South Asian	0.0000996	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest.
• Pathway: Gastric cancer - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Cell cycle - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Integrated Cancer Pathway;Transcriptional activity of SMAD2-SMAD3-SMAD4 heterotrimer;Signaling Pathways in Glioblastoma;Vitamin D Receptor Pathway;Senescence-Associated Secretory Phenotype (SASP);TGF-beta Signaling Pathway;G1 to S cell cycle control;cell cycle: g1/s check point;cyclins and cell cycle regulation;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;Hedgehog;Cyclin D associated events in G1;G1 Phase;Mitotic G1-G1/S phases;Cellular responses to external stimuli;Cell Cycle;Cell Cycle, Mitotic;Validated targets of C-MYC transcriptional repression;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.406

Intolerance Scores

• loftool: 0.383
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.502
• hipred: Y
• hipred_score: 0.677
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdkn2b
• Phenotype: renal/urinary system phenotype; immune system phenotype; neoplasm; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;G2/M transition of mitotic cell cycle;cell cycle arrest;mitotic cell cycle checkpoint;negative regulation of cell population proliferation;megakaryocyte differentiation;positive regulation of transforming growth factor beta receptor signaling pathway;cellular response to extracellular stimulus;cellular response to nutrient;negative regulation of phosphorylation;negative regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of transcription by RNA polymerase II;spleen development;negative regulation of epithelial cell proliferation;cellular senescence;negative regulation of G1/S transition of mitotic cell cycle
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: cyclin-dependent protein serine/threonine kinase inhibitor activity;protein binding;protein kinase binding