GSDMD

Chr 8

gasdermin D

Also known as: DF5L, DFNA5L, FKSG10, GSDMDC1

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.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
1336
Pubs (1 yr)
61
P/LP submissions
0%
P/LP missense
1.45
LOEUF
Mechanism
Clinical SummaryGSDMD
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 94 VUS of 200 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.45LOEUF
pLI 0.000
Z-score 0.02
OE 1.00 (0.701.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.60Z-score
OE missense 0.90 (0.811.00)
261 obs / 289.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.00 (0.701.45)
00.351.4
Missense OE0.90 (0.811.00)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 20 / 20.1Missense obs/exp: 261 / 289.7Syn Z: -0.14

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic5
VUS94
Likely Benign10
Benign7
55
Pathogenic
5
Likely Pathogenic
94
VUS
10
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
5
0
5
VUS
0
89
5
0
94
Likely Benign
0
6
0
4
10
Benign
0
4
2
1
7
Total099675171

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

View in ClinVar →

Protein Context — Lollipop Plot

GSDMD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
GPX4 in cell death, autophagy, and disease.
Xie Y et al.·Autophagy
2023Review
NLRP3 and pyroptosis blockers for treating inflammatory diseases.
Coll RC et al.·Trends Pharmacol Sci
2022Review
An overview of the non-canonical inflammasome.
Downs KP et al.·Mol Aspects Med
2020Review
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
Top 5 results · since 2015Search PubMed ↗