GSDMC

Chr 8

gasdermin C

Also known as: MLZE

NCBI Gene: 56169 ENSG00000147697 UniProt: Q9BYG8 OMIM: 608384

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables wide pore channel activity. Involved in pyroptotic inflammatory response. Located in cytoplasm. Is active in plasma membrane. Biomarker of lung adenocarcinoma. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in GSDMC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

712 rare PASS variants

Rare truncating (LoF)

1 in 380

121 rare PASS variants

Rare synonymous (reference)

1 in 190

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GSDMC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 89	1 in 900
South Asian	~43k	1 in 55	1 in 1,000
Remaining (unassigned)	~30k	1 in 62	1 in 790
European (Finnish)	~27k	1 in 340	1 in 4,400
Admixed American	~22k	1 in 79	1 in 400
African / African American	~21k	1 in 80	1 in 470
East Asian	~20k	1 in 92	1 in 690
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 59	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 13.? see exons ↓