GABRE

Chr X

gamma-aminobutyric acid type A receptor subunit epsilon

NCBI Gene: 2564 ENSG00000102287 UniProt: P78334

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

The product of this gene belongs to the ligand-gated ionic channel (TC 1.A.9) family. It encodes the gamma-aminobutyric acid (GABA) A receptor which is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes an epsilon subunit. It is mapped to chromosome Xq28 in a cluster comprised of genes encoding alpha 3, beta 4 and theta subunits of the same receptor. Alternatively spliced transcript variants have been identified, but only one is thought to encode a protein. [provided by RefSeq, Oct 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.51

OE 0.57 (0.33–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.01 (0.91–1.14)

211 obs / 208.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.33–1.02)

0≤0.351.4

Missense OE?1.01 (0.91–1.14)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 8 / 14.1Missense obs/exp: 211 / 208.1Syn Z: 0.61

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

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

462 rare PASS variants

Rare truncating (LoF)

1 in 3,300

48 rare PASS variants

Rare synonymous (reference)

1 in 260

164 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GABRE. 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)	~561k	1 in 140	1 in 2,800
South Asian	~36k	1 in 130	≈ 1 in 12,000
Remaining (unassigned)	~31k	1 in 110	≈ 1 in 15,000
European (Finnish)	~27k	1 in 590	≈ 1 in 27,000
Admixed American	~23k	1 in 150	≈ 1 in 21,000
African / African American	~21k	1 in 95	1 in 2,700
East Asian	~20k	1 in 83	≈ 1 in 10,000
Ashkenazi Jewish	~13k	1 in 560	none seen
Middle Eastern	~2,758	1 in 83	none seen

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): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓