CDKN2C

Chr 1

cyclin dependent kinase inhibitor 2C

Also known as: INK4C, p18, p18-INK4C

NCBI Gene: 1031ENSG00000123080UniProt: P42773

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]

34
ClinVar variants
8
Pathogenic / LP
0.40
pLI score
1
Active trials
Clinical Summary— CDKN2C
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 21 VUS of 34 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.395
Z-score 1.66
OE 0.20 (0.07–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.08Z-score
OE missense 0.69 (0.57–0.85)
67 obs / 97.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.07–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.57–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.78
0≤1.21.6
LoF obs/exp: 1 / 5.0Missense obs/exp: 67 / 97.0Syn Z: 1.14

ClinVar Variant Classifications

34 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Parathyroid Carcinoma.
Cetani F et al.·Front Horm Res
2019Review
MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma.
Liang J et al.·Drug Resist Updat
2024
Molecular basis of multiple myeloma.
Nižňanská D et al.·Klin Onkol
2024Review
Deletions of CDKN2C in multiple myeloma: biological and clinical implications.
Leone PE et al.·Clin Cancer Res
2008
Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.
Grubbs EG et al.·Thyroid
2016
Role of CDKN2C Fluorescence In Situ Hybridization in the Management of Medullary Thyroid Carcinoma.
El Naofal M et al.·Ann Clin Lab Sci
2017
Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism.
Mazarico-Altisent I et al.·J Endocrinol Invest
2023
Clinical significance of cyclin-dependent kinase inhibitor 2C expression in cancers: from small cell lung carcinoma to pan-cancers.
Li GS et al.·BMC Pulm Med
2022
Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort.
Mazarico-Altisent I et al.·Front Endocrinol (Lausanne)
2023Cohort
Clinical MEN-1 Among a Large Cohort of Patients With Acromegaly.
Nachtigall LB et al.·J Clin Endocrinol Metab
2020Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Case of CDKN2C/CIC Null Epithelioid Leiomyosarcoma With a Low-grade Component Indistinguishable From Leiomyoma.
Codispoti N et al.·Int J Gynecol Pathol
2025
Enhancing radiosensitivity in osteosarcoma via CDKN2C overexpression: A mechanism involving G1 phase arrest mediated by inhibition of CDK4 expression and Thr172 phosphorylation.
Lian Q et al.·Biochem Biophys Res Commun
2024Functional
Oxidative modification of miR-30c promotes cardiac fibroblast proliferation via CDKN2C mismatch.
Chang W et al.·Sci Rep
2024
CBX8 promotes lung adenocarcinoma growth and metastasis through transcriptional repression of CDKN2C and SCEL.
Chen H et al.·J Cell Physiol
2023
The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high-grade cervical lesion detection in liquid-based cytology.
Causin RL et al.·Cancer Cytopathol
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Anatomic Stage IV Breast Cancer AJCC v8Metastatic HER2-Negative Breast CarcinomaMetastatic Hormone Receptor-Positive Breast Carcinoma

A Vaccine (STEMVAC) With Standard Endocrine-Based Therapy or Chemotherapy for the Treatment of Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

RECRUITING
NCT07112053Phase PHASE2University of WashingtonStarted 2025-11-17
CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineCapecitabineComputed Tomography

External Resources

Links to major genomics databases and tools