GABRB2

Chr 5

gamma-aminobutyric acid type A receptor subunit beta2

Also known as: DEE92, ICEE2

NCBI Gene: 2561ENSG00000145864UniProt: P47870

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 2 subunit. It is mapped to chromosome 5q34 in a cluster comprised of genes encoding alpha 1 and gamma 2 subunits of the GABA A receptor. Alternative splicing of this gene generates 2 transcript variants, differing by a 114 bp insertion. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtEpileptic encephalopathy, infantile or early childhood, 2
663
ClinVar variants
57
Pathogenic / LP
0.85
pLI score
1
Active trials
Clinical Summary— GABRB2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
57 Pathogenic / Likely Pathogenic· 170 VUS of 663 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
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.
0.39LOEUF
pLI 0.849
Z-score 3.76
OE 0.17 (0.08–0.39)
Moderately constrained

More LoF-intolerant than ~75% 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.
3.40Z-score
OE missense 0.45 (0.39–0.52)
133 obs / 298.0 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.0.17 (0.08–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.45 (0.39–0.52)
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.1.11
0≤1.21.6
LoF obs/exp: 4 / 23.8Missense obs/exp: 133 / 298.0Syn Z: -0.92

ClinVar Variant Classifications

663 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic34
VUS170
Likely Benign172
Benign46
Conflicting8
23
Pathogenic
34
Likely Pathogenic
170
VUS
172
Likely Benign
46
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
10
13
0
23
Likely Pathogenic
0
32
2
0
34
VUS
8
140
20
2
170
Likely Benign
0
12
74
86
172
Benign
0
14
27
5
46
Conflicting
—8
Total820813693453

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRB2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GABRB2-related epilepsy and intellectual disability

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

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
Molecular and clinical descriptions of patients with GABA(A) receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation.
Maillard PY et al.·Epilepsia
2022Review
Distinct neurodevelopmental and epileptic phenotypes associated with gain- and loss-of-function GABRB2 variants.
Mohammadi NA et al.·EBioMedicine
2024
Understanding paralogous epilepsy-associated GABA(A) receptor variants: Clinical implications, mechanisms, and potential pitfalls.
Kan ASH et al.·Proc Natl Acad Sci U S A
2024Functional
GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations.
Chen J et al.·Biochem Soc Trans
2009
A novel variant in GABRB2 associated with intellectual disability and epilepsy.
Srivastava S et al.·Am J Med Genet A
2014
Relationship between GABRB2 gene polymorphisms and schizophrenia susceptibility: a case-control study and in silico analyses.
Heidari Nia M et al.·Int J Neurosci
2022
Phenotypic spectrum of patients with GABRB2 variants: from mild febrile seizures to severe epileptic encephalopathy.
Yang Y et al.·Dev Med Child Neurol
2020Cohort
A de novo GABRB2 variant associated with myoclonic status epilepticus and rhythmic high-amplitude delta with superimposed (poly) spikes (RHADS).
Nishikawa A et al.·Epileptic Disord
2020Case report
Characterization of the GABRB2-Associated Neurodevelopmental Disorders.
El Achkar CM et al.·Ann Neurol
2021
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
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet

External Resources

Links to major genomics databases and tools