GABRR2

Chr 6

gamma-aminobutyric acid type A receptor subunit rho2

NCBI Gene: 2570ENSG00000111886UniProt: P28476

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]

111
ClinVar variants
14
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GABRR2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 87 VUS of 111 total submissions

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.
0.89LOEUF
pLI 0.000
Z-score 1.93
OE 0.54 (0.34–0.89)
Tolerant

Typical tolerance to LoF variation

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.
0.30Z-score
OE missense 0.95 (0.86–1.05)
268 obs / 282.0 exp
Tolerant

Mild missense constraint

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.0.54 (0.34–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.05)
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.0.97
0≤1.21.6
LoF obs/exp: 11 / 20.4Missense obs/exp: 268 / 282.0Syn Z: 0.25

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS87
Likely Benign5
Benign4
Conflicting1
14
Pathogenic
87
VUS
5
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
72
15
0
87
Likely Benign
0
2
1
2
5
Benign
0
2
0
2
4
Conflicting
—1
Total076304111

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRR2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population.
Kumari R et al.·Clin Chim Acta
2011
Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People.
Ma Z et al.·Cell Mol Neurobiol
2017
Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.
Jiménez-Jiménez FJ et al.·Pharmacogenomics J
2018
Evaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: a follow-up study in antipsychotic-naïve patients with first-episode psychosis.
Ota VK et al.·J Psychiatr Res
2014Cohort
Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for essential tremor.
García-Martín E et al.·J Neurol
2011
Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.
Petazzi P et al.·RNA Biol
2013Functional
Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome and seizure types: a case-control study.
Cavalleri GL et al.·Lancet Neurol
2007
Top 10 resultsSearch PubMed ↗
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