CDKN1B

cyclin dependent kinase inhibitor 1B

Basic information

Region (hg38): 12:12685498-12722369

Links

ENSG00000111276 ∙ NCBI:1027 ∙ OMIM:600778 ∙ HGNC:1785 ∙ Uniprot:P46527 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple endocrine neoplasia type 4 (Supportive), mode of inheritance: AD
• multiple endocrine neoplasia type 4 (Strong), mode of inheritance: AD
• hereditary nonpolyposis colon cancer (Limited), mode of inheritance: AR
• multiple endocrine neoplasia type 4 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple endocrine neoplasia, type IV	AD	Endocrine; Oncologic	Surveillance and risk awareness may allow prompt detection and treatment of associated neoplasms (in affected individuals, these have been reported as including primary hyperparathyroidism likely due to underlying neoplasm, pituitary adenoma, and renal angiomyolipoma), which may decrease associated morbidity and mortality	Endocrine; Oncologic	17030811; 20507346; 20824794; 21289244; 22129891; 23555276; 24819502

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDKN1B gene.

• Multiple endocrine neoplasia type 4 (51 variants)
• Hereditary cancer-predisposing syndrome (26 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDKN1B 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			2	175	2	179
missense			431	4	1	436
nonsense	23	4				27
start loss			2			2
frameshift	40	3	16			59
inframe indel			8			8
splice donor/acceptor (+/-2bp)		2	3			5
splice region			5	13		18
non coding		1	43	31	14	89
Total	63	10	505	210	17

Variants in CDKN1B

This is a list of pathogenic ClinVar variants found in the CDKN1B region.

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

Position	Type	Phenotype	Significance	ClinVar
12-12717002-C-A		Multiple endocrine neoplasia type 4	Benign (Dec 04, 2020)
12-12717038-G-T			Benign (Jan 10, 2019)
12-12717369-T-G		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 13, 2018)
12-12717383-CCCTT-C		Multiple endocrine neoplasia type 4	Pathogenic (Mar 01, 2013)
12-12717417-G-A		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 13, 2018)
12-12717429-T-C		Multiple endocrine neoplasia type 4	Benign (Jan 13, 2018)
12-12717454-C-G		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 12, 2018)
12-12717454-C-T		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 12, 2018)
12-12717466-G-A		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 13, 2018)
12-12717469-C-T		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 12, 2018)
12-12717474-C-T		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 12, 2018)
12-12717504-A-G		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 13, 2018)
12-12717566-AC-A		Multiple endocrine neoplasia	Uncertain significance (Jun 14, 2016)
12-12717574-C-G		Multiple endocrine neoplasia type 4	Benign (Oct 01, 2022)
12-12717586-C-G		Multiple endocrine neoplasia type 4	Benign (Jan 12, 2018)
12-12717614-C-T		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 13, 2018)
12-12717618-C-T		Multiple endocrine neoplasia type 4	Uncertain significance (Jan 12, 2018)
12-12717638-C-T		Multiple endocrine neoplasia type 4	Likely benign (Jun 23, 2018)
12-12717714-C-T		Multiple endocrine neoplasia type 4	Benign (Dec 23, 2021)
12-12717760-C-T		Primary hyperparathyroidism • Multiple endocrine neoplasia type 4 • CDKN1B-related disorder	Conflicting classifications of pathogenicity (Mar 06, 2024)
12-12717761-T-C		Multiple endocrine neoplasia type 4	Benign (Jan 29, 2024)
12-12717767-G-A		Hereditary cancer-predisposing syndrome • Multiple endocrine neoplasia type 4	Uncertain significance (Dec 12, 2019)
12-12717804-G-C			Uncertain significance (Jan 12, 2023)
12-12717807-CGAGA-C		Multiple endocrine neoplasia type 4 • Primary hyperparathyroidism • Multiple endocrine neoplasia • not specified • CDKN1B-related disorder	Conflicting classifications of pathogenicity (Jul 31, 2024)
12-12717808-G-A			Uncertain significance (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDKN1B	protein_coding	protein_coding	ENST00000228872	2	7314

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.624	0.370	125727	0	6	125733	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.85	164	110	1.50	0.00000516	1295
Missense in Polyphen		31	26.134	1.1862		326
Synonymous	-5.17	88	44.2	1.99	0.00000222	384
Loss of Function	2.17	1	7.36	0.136	3.19e-7	91

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.00	0.00
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A- CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. {ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:28666995}.
• Disease: DISEASE: Multiple endocrine neoplasia 4 (MEN4) [MIM:610755]: Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2. {ECO:0000269|PubMed:17030811}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Cell cycle - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Cell Cycle;miRNA Regulation of DNA Damage Response;miRNAs involved in DNA damage response;Integrated Cancer Pathway;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Human Thyroid Stimulating Hormone (TSH) signaling pathway;IL-7 Signaling Pathway;Signaling Pathways in Glioblastoma;Oncostatin M Signaling Pathway;Spinal Cord Injury;Retinoblastoma (RB) in Cancer;Primary Focal Segmental Glomerulosclerosis FSGS;Aryl Hydrocarbon Receptor;Apoptosis-related network due to altered Notch3 in ovarian cancer;Aryl Hydrocarbon Receptor Pathway;Vitamin D Receptor Pathway;Nuclear Receptors Meta-Pathway;Ovarian Infertility Genes;Imatinib and Chronic Myeloid Leukemia;regulation of p27 phosphorylation during cell cycle progression;Association Between Physico-Chemical Features and Toxicity Associated Pathways;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miR-222 in Exercise-Induced Cardiac Growth;Oxidative Damage;miRNA regulation of prostate cancer signaling pathways;Liver steatosis AOP;PI3K-Akt Signaling Pathway;G1 to S cell cycle control;Senescence and Autophagy in Cancer;ErbB Signaling Pathway;DNA Damage Response;DNA Damage Response (only ATM dependent);Signaling by PTK6;RAGE;Disease;Signal Transduction;Gene expression (Transcription);influence of ras and rho proteins on g1 to s transition;cell cycle: g1/s check point;pten dependent cell cycle arrest and apoptosis;cyclins and cell cycle regulation;cdk regulation of dna replication;ctcf: first multivalent nuclear factor;Generic Transcription Pathway;DNA Damage/Telomere Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;p53-Dependent G1 DNA Damage Response;p53-Dependent G1/S DNA damage checkpoint;G1/S DNA Damage Checkpoints;Cell Cycle Checkpoints;Hedgehog;Cyclin D associated events in G1;G1 Phase;SCF(Skp2)-mediated degradation of p27/p21;Cyclin E associated events during G1/S transition ;PTK6 Regulates Cell Cycle;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;S Phase;RHO GTPases activate CIT;Cellular responses to external stimuli;RHO GTPase Effectors;Signaling by Rho GTPases;TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest;TP53 Regulates Transcription of Cell Cycle Genes;PIP3 activates AKT signaling;FOXA1 transcription factor network;Signaling by Non-Receptor Tyrosine Kinases;G1/S Transition;C-MYB transcription factor network;Transcriptional Regulation by TP53;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Cell Cycle;AKT phosphorylates targets in the cytosol;Cell Cycle, Mitotic;Intracellular signaling by second messengers;Notch-mediated HES/HEY network;Diseases of signal transduction;Validated targets of C-MYC transcriptional repression;Regulation of Telomerase;AP-1 transcription factor network;FoxO family signaling;Class I PI3K signaling events mediated by Akt;Regulation of retinoblastoma protein;E2F transcription factor network;Integrins in angiogenesis;RhoA signaling pathway;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.689

Intolerance Scores

• loftool: 0.213
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.809
• hipred: Y
• hipred_score: 0.783
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.628

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdkn1b
• Phenotype: embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive 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); pigmentation phenotype; neoplasm; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; growth/size/body region 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); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;G1/S transition of mitotic cell cycle;response to hypoxia;placenta development;potassium ion transport;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;cell cycle arrest;regulation of exit from mitosis;Notch signaling pathway;heart development;sensory perception of sound;positive regulation of cell population proliferation;negative regulation of cell population proliferation;response to glucose;positive regulation of cell death;negative regulation of cell growth;positive regulation of microtubule polymerization;response to estradiol;negative regulation of kinase activity;negative regulation of phosphorylation;response to drug;negative regulation of apoptotic process;response to amino acid;response to peptide hormone;positive regulation of protein catabolic process;negative regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of cyclin-dependent protein serine/threonine kinase activity;negative regulation of cell cycle;positive regulation of cell cycle;negative regulation of transcription, DNA-templated;negative regulation of mitotic cell cycle;response to cadmium ion;autophagic cell death;inner ear development;negative regulation of cellular component movement;negative regulation of epithelial cell proliferation involved in prostate gland development;cellular response to antibiotic;cellular response to lithium ion;cellular response to organic cyclic compound;mitotic cell cycle arrest;regulation of lens fiber cell differentiation;negative regulation of cyclin-dependent protein kinase activity;negative regulation of vascular smooth muscle cell proliferation;negative regulation of cardiac muscle tissue regeneration
• Cellular component: nucleus;nucleoplasm;cytoplasm;endosome;cytosol;Cul4A-RING E3 ubiquitin ligase complex;intracellular membrane-bounded organelle
• Molecular function: cyclin-dependent protein serine/threonine kinase activity;protein kinase inhibitor activity;cyclin-dependent protein serine/threonine kinase inhibitor activity;transforming growth factor beta receptor, cytoplasmic mediator activity;protein binding;protein kinase binding;protein phosphatase binding;cyclin binding;Hsp70 protein binding;protein-containing complex binding;chaperone binding