CDKN2D

protein-coding

cyclin dependent kinase inhibitor 2D, 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 form a stable complex 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. The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. The negative regulation of the cell cycle involved in this protein was shown to participate in repressing neuronal proliferation, as well as spermatogenesis. Two alternatively spliced variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001800.4

Inheritance

—

ClinVar variants

U:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:10,566,460-10,569,059

External References & Databases

Ensembl (ENSG00000129355)

Transcript & Mutation Effects

hg38 • Region Span ~2.6 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 CDKN2D variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001800.4. 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						0
missense			14 clinvar			14
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	14	0	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001800.4	RefSeq	NP_001791.1	2	MANE Select
ENST00000393599.3	Ensembl	ENSP00000377224.1	2	MANE Select
NM_079421.3	RefSeq	NP_524145.1	2	Standard
ENST00000335766.2	Ensembl	ENSP00000337056.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell cycle - Homo sapiens (human)
FoxO signaling pathway - Homo sapiens (human)
Vitamin D Receptor Pathway
G1 to S cell cycle control
cyclins and cell cycle regulation

Biological Process

regulation of cyclin-dependent protein serine/threonine kinase activity
G1/S transition of mitotic cell cycle
DNA synthesis involved in DNA repair
cell cycle arrest
sensory perception of sound

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
cyclin D2-CDK4 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393599
Coding exons: 2
Length: 2598
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	62	92.7	0.669	0.00000537	1038
Missense (PolyPhen)		18	32.34	0.55659		345
Synonymous	0.847	35	42.0	0.834	0.00000272	381
Loss of Function	1.27	0	1.89	0.00	8.02e-8	26

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	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interacts strongly with CDK4 and CDK6 and inhibits them. {ECO:0000269|PubMed:7739548, ECO:0000269|PubMed:8741839}.;

Recessive Scores

pRec: 0.181

Intolerance Scores

RVIS EVS: -0.03
RVIS percentile EVS: 51.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.975

Gene Damage Prediction

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