GSDME

Chr 7

gasdermin E

Also known as: DFNA5, ICERE-1

NCBI Gene: 1687ENSG00000105928UniProt: O60443

Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal dominant, 5
476
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GSDME
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 216 VUS of 476 total submissions
Some data sources returned errors (2)

omim: Error: OMIM fetch failed: 429

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.13LOEUF
pLI 0.000
Z-score 1.12
OE 0.74 (0.50–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.84Z-score
OE missense 1.15 (1.04–1.26)
304 obs / 265.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.50–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.04–1.26)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 16 / 21.6Missense obs/exp: 304 / 265.4Syn Z: -0.87

ClinVar Variant Classifications

476 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic6
VUS216
Likely Benign107
Benign78
Conflicting33
36
Pathogenic
6
Likely Pathogenic
216
VUS
107
Likely Benign
78
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
34
0
36
Likely Pathogenic
1
1
4
0
6
VUS
8
167
38
3
216
Likely Benign
0
6
56
45
107
Benign
0
6
66
6
78
Conflicting
—33
Total1118019854476

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

View in ClinVar →

Protein Context — Lollipop Plot

GSDME · protein map & ClinVar variants

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

Gene2Phenotype Curations

GSDME-related deafness

strong
ADLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — GSDME
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools