GABRQ

Chr X

gamma-aminobutyric acid type A receptor subunit theta

Also known as: THETA

NCBI Gene: 55879 ENSG00000268089 UniProt: Q9UN88 OMIM: 300349

The protein encodes the theta subunit of GABA-A receptors, which are heteropentameric chloride channels that mediate fast inhibitory synaptic transmission in the central nervous system by allowing chloride influx when activated by GABA. Mutations cause X-linked intellectual disability and epilepsy through a gain-of-function mechanism that disrupts normal inhibitory neurotransmission. The gene is located on chromosome Xq28 and follows X-linked inheritance.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes the theta subunit of the GABA A receptor. The gene is mapped to chromosome Xq28 in a cluster of genes including those that encode the alpha 3 and epsilon subunits of the GABA A receptor. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.004

Z-score 2.38

OE 0.39 (0.22–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.90 (0.81–1.00)

246 obs / 273.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.22–0.74)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 7 / 17.9Missense obs/exp: 246 / 273.0Syn Z: 1.71

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

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

559 rare PASS variants

Rare truncating (LoF)

1 in 2,500

67 rare PASS variants

Rare synonymous (reference)

1 in 490

201 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GABRQ. 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 170	1 in 3,000
South Asian	~36k	1 in 110	1 in 7,100
Remaining (unassigned)	~31k	1 in 120	1 in 3,800
European (Finnish)	~27k	1 in 530	≈ 1 in 9,000
Admixed American	~23k	1 in 100	1 in 3,700
African / African American	~21k	1 in 99	1 in 1,500
East Asian	~20k	1 in 120	1 in 610
Ashkenazi Jewish	~13k	1 in 530	none seen
Middle Eastern	~2,758	1 in 130	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): 8 of 9 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 9.? see exons ↓