CDKN2C

protein-coding

cyclin dependent kinase inhibitor 2C, the group of Ankyrin repeat domain containing

Gene summary

The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_078626.3

Inheritance

—

ClinVar variants

P:1U:23B:9

Top phenotype

Multiple myeloma

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr1:50,960,745-50,974,634

External References & Databases

Ensembl (ENSG00000123080)

Transcript & Mutation Effects

hg38 • Region Span ~13.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDKN2C variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 21

not providedTotal: 8

Multiple myelomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_078626.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar	1 clinvar	8
missense		1 clinvar	17 clinvar	2 clinvar		20
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	23	8	1	33

Highest pathogenic variant AF is 6.840441e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_078626.3	RefSeq	NP_523240.1	2	MANE Select
ENST00000371761.4	Ensembl	ENSP00000360826.3	2	MANE Select
NM_001262.3	RefSeq	NP_001253.1	2	Standard
NM_001429675.1	RefSeq	NP_001416604.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cushing,s syndrome - Homo sapiens (human)
Cell cycle - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)
Transcriptional misregulation in cancer - Homo sapiens (human)
Signaling Pathways in Glioblastoma

Biological Process

regulation of cyclin-dependent protein serine/threonine kinase activity
G1/S transition of mitotic cell cycle
cell cycle arrest
negative regulation of cell population proliferation
negative regulation of cell growth

Molecular Function

cyclin-dependent protein serine/threonine kinase inhibitor activity
protein binding
protein kinase binding

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262662
Coding exons: 2
Length: 13889
Individuals with no LoFs: 125746
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125748
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	67	97.0	0.691	0.00000483	1100
Missense (PolyPhen)		16	34.358	0.46569		422
Synonymous	1.14	33	42.5	0.777	0.00000231	350
Loss of Function	1.66	1	4.99	0.200	2.97e-7	54

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB.;

Recessive Scores

pRec: 0.230

Intolerance Scores

LoFtool: 0.321
RVIS EVS: 0.06
RVIS percentile EVS: 58.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.852

Gene Damage Prediction

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