GSDMD

Chr 8

gasdermin D

Also known as: DF5L, DFNA5L, FKSG10, GSDMDC1

NCBI Gene: 79792 ENSG00000104518 OMIM: 617042

Gasdermin D is a precursor of a pore-forming protein that plays a key role in host defense against pathogen infection by forming membrane pores and triggering pyroptosis (a form of inflammatory cell death). Mutations cause familial keratoderma with inflammatory lesions, inherited in an autosomal dominant pattern. This gene shows very low constraint against loss-of-function variants, suggesting such mutations are well-tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

LOEUF 1.45

Clinical Summary— GSDMD

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

63 VUS of 95 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.45LOEUF

pLI 0.000

Z-score 0.02

OE 1.00 (0.70–1.45)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.60Z-score

OE missense 0.90 (0.81–1.00)

261 obs / 289.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.00 (0.70–1.45)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 20 / 20.1Missense obs/exp: 261 / 289.7Syn Z: -0.14

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

VUS63

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	63	63
Likely Benign	3	3
Benign	0	0
Total	66	66

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

View in ClinVar →

4 pathogenic / likely-pathogenic (of 5) ClinVar copy-number / structural variants overlap GSDMD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →