GABRQ

Chr X

gamma-aminobutyric acid type A receptor subunit theta

Also known as: THETA

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.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
5
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.74
LOEUF
GOF
Mechanism· predicted
Clinical SummaryGABRQ
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.004
Z-score 2.38
OE 0.39 (0.220.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.58Z-score
OE missense 0.90 (0.811.00)
246 obs / 273.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.220.74)
00.351.4
Missense OE0.90 (0.811.00)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 7 / 17.9Missense obs/exp: 246 / 273.0Syn Z: 1.71
DN
0.81top 10%
GOF
0.86top 5%
LOF
0.1697th %ile

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

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GABRQ · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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