GABBR1

Chr 6AD

gamma-aminobutyric acid type B receptor subunit 1

Also known as: GABABR1, GABBR1-3, GB1, GPRC3A, NEDLC

NCBI Gene: 2550ENSG00000204681UniProt: Q9UBS5

This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with language delay and variable cognitive abnormalitiesMIM #620502
AD
165
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GABBR1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 136 VUS of 165 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.22LOEUF
pLI 1.000
Z-score 5.98
OE 0.11 (0.06–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
4.82Z-score
OE missense 0.42 (0.38–0.47)
236 obs / 555.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.11 (0.06–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.38–0.47)
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.0.92
0≤1.21.6
LoF obs/exp: 6 / 53.0Missense obs/exp: 236 / 555.8Syn Z: 0.89

ClinVar Variant Classifications

165 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic8
VUS136
Likely Benign12
Benign3
Conflicting1
5
Pathogenic
8
Likely Pathogenic
136
VUS
12
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
7
1
0
8
VUS
12
112
10
2
136
Likely Benign
0
2
1
9
12
Benign
0
0
0
3
3
Conflicting
—1
Total121211714165

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

View in ClinVar →

Protein Context — Lollipop Plot

GABBR1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GABBR1-related neurodevelopmental disorder

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with language delay and variable cognitive abnormalities

MIM #620502

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Organ-specific proteomic aging clocks predict disease and longevity across diverse populations.
Wang Y et al.·Nat Aging
2026
Bisphenol A promotes OSCC progression via GABBR1-mediated MAPK signaling and macrophage polarization: A network toxicology based study.
He Q et al.·Ecotoxicol Environ Saf
2025
The neurotransmitter receptor Gabbr1 regulates proliferation and function of hematopoietic stem and progenitor cells.
Shao L et al.·Blood
2021
GABBR1 monoallelic de novo variants linked to neurodevelopmental delay and epilepsy.
Cediel ML et al.·Am J Hum Genet
2022
The GABBR1 locus and the G1465A variant is not associated with temporal lobe epilepsy preceded by febrile seizures.
Ma S et al.·BMC Med Genet
2005
The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.
Toikumo S et al.·J Clin Invest
2025
GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations.
Enoch MA et al.·Alcohol Clin Exp Res
2016
Transcriptomic and network analysis identifies shared pathways across Alzheimer's disease and vascular dementia.
Zheng C et al.·Brain Res
2025
The gene encoding GABBR1 is not associated with childhood absence epilepsy in the Chinese Han population.
Lu J et al.·Neurosci Lett
2003
Characterization of genetic and phenotypic heterogeneity of obstructive sleep apnea using electronic health records.
Veatch OJ et al.·BMC Med Genomics
2020
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