CCND2

Chr 12

cyclin D2

Also known as: KIAK0002, MPPH3

NCBI Gene: 894ENSG00000118971UniProt: P30279

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK4 or CDK6 and functions as a regulatory subunit of the complex, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors. Mutations in this gene are associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3). [provided by RefSeq, Sep 2014]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMegalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

Clinical highlights

Gene-disease validity (ClinGen)
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
111
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.23
LOEUF· LoF intol.
GOF*
Mechanism· G2P
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GeneReview available — CCND2
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.23LOEUF
pLI 0.987
Z-score 3.35
OE 0.00 (0.00–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.13Z-score
OE missense 0.54 (0.45–0.64)
91 obs / 169.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.23)
0≤0.351.4
Missense OE?0.54 (0.45–0.64)
0≤0.61.4
Synonymous OE?0.89
0≤1.21.6
LoF obs/exp: 0 / 13.0Missense obs/exp: 91 / 169.0Syn Z: 0.78

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CCND2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients