protein
Gamma-aminobutyric acid receptor subunit beta-3
Gene
GABRB3
Organism
Homo sapiens(9606)
Length
473 aa
Mass
54,116 Da
GABRB3 encodes the beta-3 subunit of GABA(A) receptors, which are pentameric ligand-gated chloride channels fundamental to inhibitory neurotransmission in the brain (UniProt: P28472). The GABA-binding site forms at interfaces between alpha and beta subunits; upon GABA activation, chloride influx hyperpolarizes neurons and suppresses action potential generation. Beta-3-containing receptors localize to both synaptic and extrasynaptic sites, contributing to phasic and tonic inhibition respectively, and also facilitate synaptogenesis and somatosensory signaling (UniProt: P28472).
GABRB3 variants cause epilepsy-spectrum disorders. Mutations are associated with childhood absence epilepsy 5 (ECA5), characterized by onset around age 6–7 with frequent absence seizures and 3-Hz spike-wave discharges, and developmental and epileptic encephalopathy 43 (DEE43), an autosomal dominant severe early-onset epilepsy with refractory seizures and neurodevelopmental impairment (UniProt: P28472).
GABRB3 is classified as SFARI Category 2 (strong candidate) and carries syndromic annotation, indicating robust evidence for association with autism spectrum disorder in the context of epilepsy or broader developmental encephalopathy (SFARI Cat 2).
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.442
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.4422 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
This protein is implicated in both ASD and Alzheimer's Disease. View all cross-disease proteins →
Related Publications
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Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:14993607, PubMed:18514161, PubMed:22243422, PubMed:22303015, PubMed:24909990, PubMed:26950270, PubMed:30602789). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:24909990, PubMed:30140029, PubMed:30602789). GABAARs containing beta-3/GABRB3 subunit are found at both synaptic and extrasynaptic sites (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:14993607, PubMed:22303015, PubMed:26950270, PubMed:30602789). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (PubMed:22303015, PubMed:26950270). GABAARs containing alpha-1 and beta-3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:25489750). Extrasynaptic beta-3 receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs containing alpha-1, beta-3 and epsilon subunits may also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:18281286, PubMed:24909990, PubMed:35355020). Plays an important role in somatosensation and in the production of antinociception (By similarity)
Disease associations
Epilepsy, childhood absence 5ECA5
A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood.
Developmental and epileptic encephalopathy 43DEE43
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE43 inheritance is autosomal dominant.
Sources
Last updated 5/8/2026, 1:06:26 AM