GABRB1

Chr 4AD

gamma-aminobutyric acid type A receptor subunit beta1

Also known as: DEE45, EIEE45

NCBI Gene: 2560ENSG00000163288UniProt: P18505

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 GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 45MIM #617153
AD
470
ClinVar variants
24
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GABRB1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 222 VUS of 470 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.31LOEUF
pLI 0.981
Z-score 4.11
OE 0.12 (0.05–0.31)
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.
2.65Z-score
OE missense 0.55 (0.49–0.63)
156 obs / 281.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.12 (0.05–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.49–0.63)
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.1.12
0≤1.21.6
LoF obs/exp: 3 / 25.3Missense obs/exp: 156 / 281.1Syn Z: -1.00

ClinVar Variant Classifications

470 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic5
VUS222
Likely Benign194
Benign24
Conflicting4
19
Pathogenic
5
Likely Pathogenic
222
VUS
194
Likely Benign
24
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
18
0
19
Likely Pathogenic
0
4
1
0
5
VUS
5
188
28
1
222
Likely Benign
0
2
83
109
194
Benign
0
1
12
11
24
Conflicting
—4
Total5196142121468

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRB1 · 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

Developmental and epileptic encephalopathy 45

MIM #617153

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variations in GABA metabolism and epilepsy.
Feng Y et al.·Seizure
2022Review
The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.
Burgess R et al.·Ann Neurol
2019
The genetic and phenotypic spectrum of GABRB1-related disorders.
Millevert C et al.·Brain
2026
GABRB1-related early onset developmental and epileptic encephalopathy: Clinical trajectory and novel de novo mutation.
Monfrini E et al.·Epileptic Disord
2023Case report
The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence.
Zhu B et al.·Neuroimage
2014
Disrupted synaptic gene expression in Fabry disease: Findings from RNA sequencing.
López-Valverde L et al.·Neurobiol Dis
2025
Genetic markers of early response to lurasidone in acute schizophrenia.
Yoshikawa A et al.·Pharmacogenomics J
2025
Routine Diagnostics Confirm Novel Neurodevelopmental Disorders.
Jauss RT et al.·Genes (Basel)
2022
Clinical application of trio-based whole-exome sequencing in idiopathic generalized epilepsy.
Lin ZJ et al.·Seizure
2024
Nongenetic and genetic predictors of haemodynamic instability induced by propofol and opioids: A retrospective clinical study.
Gu QL et al.·Br J Clin Pharmacol
2023
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