CDKN1C
Chr 11cyclin dependent kinase inhibitor 1C
Also known as: BWCR, BWS, KIP2, WBS, p57, p57Kip2
This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
Strong evidence — appropriate for clinical testing
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
1280 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 95 | 6 | 2 | 0 | 103 |
Likely Pathogenic | 22 | 4 | 0 | 0 | 26 |
VUS | 15 | 559 | 13 | 3 | 590 |
Likely Benign | 3 | 180 | 45 | 274 | 502 |
Benign | 0 | 1 | 2 | 1 | 4 |
Conflicting | — | 49 | |||
| Total | 135 | 750 | 62 | 278 | 1,274 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →27 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap CDKN1C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
CDKN1C · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGDeveloping Derived Induced Pluripotent Stem Cells as a Model to Understand Imprinted Disorders
ENROLLING BY INVITATIONMaternal Genes and Epimutations: Beckwith-Wiedemann Syndrome & Reproductive Risks
RECRUITINGExternal Resources
Links to major genomics databases and tools