CDKN2C

Chr 1

cyclin dependent kinase inhibitor 2C

Also known as: INK4C, p18, p18-INK4C

The protein is a cyclin-dependent kinase inhibitor that prevents activation of CDK4 and CDK6 kinases, thereby regulating cell cycle G1 progression and controlling cell growth. Mutations cause melanoma-pancreatic cancer syndrome with autosomal dominant inheritance, characterized by increased susceptibility to melanoma and pancreatic adenocarcinoma. The gene shows relatively low constraint to loss-of-function variants, which is consistent with its role as a tumor suppressor where heterozygous loss can contribute to cancer predisposition.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.95
Clinical SummaryCDKN2C
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
8 unique Pathogenic / Likely Pathogenic· 21 VUS of 45 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.395
Z-score 1.66
OE 0.20 (0.070.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.08Z-score
OE missense 0.69 (0.570.85)
67 obs / 97.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.070.95)
00.351.4
Missense OE0.69 (0.570.85)
00.61.4
Synonymous OE0.78
01.21.6
LoF obs/exp: 1 / 5.0Missense obs/exp: 67 / 97.0Syn Z: 1.14

ClinVar Variant Classifications

45 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic4
VUS21
Likely Benign5
4
Pathogenic
4
Likely Pathogenic
21
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
1
3
0
4
VUS
0
13
7
1
21
Likely Benign
0
1
0
4
5
Benign
0
0
0
0
0
Total01514534

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

View in ClinVar →

Protein Context — Lollipop Plot

CDKN2C · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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