GABRA5

Chr 15AD

gamma-aminobutyric acid type A receptor subunit alpha5

Also known as: DEE79, EIEE79

NCBI Gene: 2558ENSG00000186297UniProt: P31644

GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 79MIM #618559
AD
436
ClinVar variants
308
Pathogenic / LP
0.91
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GABRA5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
308 Pathogenic / Likely Pathogenic· 80 VUS of 436 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.
0.37LOEUF
pLI 0.905
Z-score 3.62
OE 0.14 (0.07–0.37)
Highly 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.
3.23Z-score
OE missense 0.46 (0.39–0.53)
127 obs / 278.8 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.0.14 (0.07–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.46 (0.39–0.53)
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.1.03
0≤1.21.6
LoF obs/exp: 3 / 20.8Missense obs/exp: 127 / 278.8Syn Z: -0.25

ClinVar Variant Classifications

436 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic299
Likely Pathogenic9
VUS80
Likely Benign35
Benign11
299
Pathogenic
9
Likely Pathogenic
80
VUS
35
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
295
0
299
Likely Pathogenic
0
2
7
0
9
VUS
2
63
14
1
80
Likely Benign
0
6
5
24
35
Benign
0
1
5
5
11
Total27632630434

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRA5 · 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 79

MIM #618559

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GABA(A) receptors as targets for treating affective and cognitive symptoms of depression.
Luscher B et al.·Trends Pharmacol Sci
2023Review
Genetic variations in GABA metabolism and epilepsy.
Feng Y et al.·Seizure
2022Review
Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice.
Syding LA et al.·Genes (Basel)
2023
De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy.
Butler KM et al.·Brain
2018
Infantile Epileptic Spasms Syndrome: Unveiling clinical and genetic variability in a case series from Argentina.
Martín ME et al.·Seizure
2025Cohort
An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population.
Hou SJ et al.·BMC Med Genomics
2021
Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes.
Frohlich J et al.·Biol Psychiatry
2019
Neurological disorder-associated genetic variants in individuals with psychogenic nonepileptic seizures.
Leu C et al.·Sci Rep
2020
Association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) and bipolar affective disorder.
Papadimitriou GN et al.·Am J Med Genet
1998
Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation.
Delahanty RJ et al.·Cell Rep
2016
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