GABRE

Chr X

gamma-aminobutyric acid type A receptor subunit epsilon

The epsilon subunit of GABA-A receptors forms part of heteropentameric chloride channels that mediate fast inhibitory neurotransmission in the brain and allow spontaneous chloride channel activity. Mutations cause early infantile epileptic encephalopathy and Ohtahara syndrome with X-linked inheritance. This gene shows low constraint to loss-of-function variants, and phenotypes may include both neurological and cardiac manifestations.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.02
Clinical SummaryGABRE
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 42 VUS of 100 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.51
OE 0.57 (0.331.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.07Z-score
OE missense 1.01 (0.911.14)
211 obs / 208.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.331.02)
00.351.4
Missense OE1.01 (0.911.14)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 8 / 14.1Missense obs/exp: 211 / 208.1Syn Z: 0.61
DN
0.77top 25%
GOF
0.76top 25%
LOF
0.2580th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

100 submitted variants in ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic2
VUS42
Likely Benign10
Benign5
41
Pathogenic
2
Likely Pathogenic
42
VUS
10
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
40
0
41
Likely Pathogenic
0
0
2
0
2
VUS
0
35
7
0
42
Likely Benign
0
4
3
3
10
Benign
0
3
0
2
5
Total142525100

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRE · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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