GSDMC
Chr 8gasdermin C
Also known as: MLZE
Gasdermin C is a pore-forming protein that, upon cleavage, creates membrane pores and triggers pyroptosis, a form of inflammatory cell death. Mutations cause autosomal dominant hearing loss, typically presenting as non-syndromic sensorineural hearing loss. The gene shows minimal constraint to loss-of-function variants, suggesting that complete loss of function may be tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
135 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 | 0 | 0 | 52 | 0 | 52 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 59 | 2 | 0 | 61 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 2 | 0 | 2 | 4 |
| Total | 0 | 65 | 55 | 2 | 122 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GSDMC · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools