CDKN2C

Chr 1

cyclin dependent kinase inhibitor 2C

Also known as: INK4C, p18, p18-INK4C

NCBI Gene: 1031ENSG00000123080UniProt: P42773OMIM: 603369

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]

OMIMResearchGenerating clinical summary…
LOEUF 0.95
Clinical Summary— CDKN2C
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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.
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ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 14 VUS of 31 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.95LOEUF
pLI 0.395
Z-score 1.66
OE 0.20 (0.07–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.08Z-score
OE missense 0.69 (0.57–0.85)
67 obs / 97.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.07–0.95)
0≤0.351.4
Missense OE?0.69 (0.57–0.85)
0≤0.61.4
Synonymous OE?0.78
0≤1.21.6
LoF obs/exp: 1 / 5.0Missense obs/exp: 67 / 97.0Syn Z: 1.14

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1
VUS14
Likely Benign5
1
Likely Pathogenic
14
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
1
0
0
1
VUS
0
13
0
1
14
Likely Benign
0
1
0
4
5
Benign
0
0
0
0
0
Total0150520

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

7 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CDKN2C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CDKN2C · 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