GSDMC

Chr 8

gasdermin C

Also known as: MLZE

NCBI Gene: 56169 ENSG00000147697 UniProt: Q9BYG8

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.

ResearchSummary from RefSeq, UniProt

Enables wide pore channel activity. Involved in pyroptotic inflammatory response. Located in cytoplasm. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.25

Clinical Summary— GSDMC

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

60 VUS of 81 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.000

Z-score 0.58

OE 0.88 (0.62–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.51Z-score

OE missense 1.09 (0.99–1.20)

286 obs / 262.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.62–1.25)

0≤0.351.4

Missense OE?1.09 (0.99–1.20)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 22 / 25.1Missense obs/exp: 286 / 262.6Syn Z: -0.13

This gene — mechanism propensity

0.6357th %ile

GOF

0.6052th %ile

LOF

0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

81 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign4

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	60	0	60
Likely Benign	4	0	4
Benign	2	2	4
Total	66	2	68

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

View in ClinVar →

53 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap GSDMC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →