Affinage

GABRB3

Gamma-aminobutyric acid receptor subunit beta-3 · UniProt P28472

Length
473 aa
Mass
54.1 kDa
Annotated
2026-04-28
71 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GABRB3 encodes the β3 subunit of GABAA receptors and is essential for inhibitory neurotransmission, receptor assembly and trafficking, inhibitory synapse development, and cortical circuit maturation. The β3 subunit governs receptor surface expression, glycosylation, channel gating kinetics, and postsynaptic clustering of γ2 subunits at inhibitory synapses; pathogenic missense variants cause either loss-of-function (reduced GABA currents, impaired surface expression, shortened open times) or gain-of-function (increased GABA potency, reduced desensitization), with these two functional classes segregating into distinct epileptic encephalopathy phenotypes of differing severity (PMID:35383156, PMID:37647766, PMID:31435640). Homozygous disruption in mice produces seizures, Angelman syndrome–like features, social behavior deficits, cerebellar hypoplasia, and loss of retinal pigmentation through cis-regulatory effects on the 15q11-13 locus (PMID:10515160, PMID:17983671, PMID:28009282). GABRB3 transcription is regulated by MeCP2, Sp1, N-Oct-3, and REST through the exon 1a promoter, and the gene resides in an imprinted domain exhibiting allele-specific replication timing and parent-of-origin–dependent expression effects (PMID:8382702, PMID:15615769, PMID:7795644, PMID:20699105).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Identifying how GABRB3 transcription is initiated revealed a strong promoter between alternative exons 1 and 1a, with Sp1 binding at overlapping start sites and developmentally regulated alternative transcripts, establishing the first cis-regulatory architecture for this gene.

    Evidence Promoter activity assays, nuclear factor footprinting, and transcript analysis in cell lines and human brain tissue

    PMID:8382702

    Open questions at the time
    • Identity of non-Sp1 nuclear factor not resolved
    • Functional consequence of signal-peptide variants from alternative exons not tested in neurons
  2. 1995 High

    Demonstrating allele-specific replication timing in the GABRB3-GABRA5 domain established that this locus is subject to parental imprinting at the chromatin level, explaining why parent-of-origin matters for GABRB3 dosage.

    Evidence BrdU incorporation/FISH replication timing assay in uniparental disomy and deletion cell lines

    PMID:7795644

    Open questions at the time
    • Whether differential replication timing translates to differential transcription was not directly shown
    • Mechanism of imprint establishment not addressed
  3. 1999 High

    Gabrb3 knockout mice exhibiting spontaneous seizures and EEG abnormalities proved that loss of the β3 subunit alone is sufficient for epileptogenesis, providing the first in vivo causal link.

    Evidence Gene knockout mouse with EEG recording and behavioral analysis

    PMID:10515160

    Open questions at the time
    • Specific circuit mechanisms underlying seizures not resolved
    • Contribution of developmental versus acute loss not distinguished
  4. 2004 High

    Showing that MeCP2 deficiency reduces GABRB3 protein in mouse brain and human Rett/Angelman/autism tissue connected epigenetic transcriptional regulation to GABRB3 dosage control, linking MeCP2 disorders mechanistically to GABAergic deficiency.

    Evidence Quantitative immunoblot, laser scanning cytometry immunofluorescence and ISH in two Mecp2-null mouse strains and human tissue microarrays

    PMID:15615769

    Open questions at the time
    • Direct MeCP2 occupancy at GABRB3 locus not shown
    • Whether MeCP2 acts as activator or derepressor at this promoter not resolved
  5. 2006 High

    Identification of N-Oct-3 and REST as transcriptional regulators of the exon 1a promoter, together with disease-associated haplotype effects, established that GABRB3 expression levels are tuned by neuron-specific and repressive transcription factors, explaining how common variants modulate epilepsy risk.

    Evidence Reporter gene assays, EMSA, and deletion series in NT2 and HEK293 cells

    PMID:16835263 PMID:22765836

    Open questions at the time
    • Chromatin-level confirmation (ChIP) for N-Oct-3 and REST binding at endogenous locus not performed
    • In vivo relevance of REST-mediated repression in neurons not tested
  6. 2007 High

    Gabrb3 knockout mice displaying social deficits, cerebellar vermal hypoplasia, locus coeruleus dendritic expansion, and hypotonia broadened the gene's role beyond seizures to social behavior, cerebellar development, and noradrenergic circuit morphology.

    Evidence Behavioral battery, morphometric analysis of cerebellum and locus coeruleus in Gabrb3−/− mice

    PMID:17156762 PMID:17983671

    Open questions at the time
    • Cell-autonomous versus circuit-level mechanisms not distinguished
    • Developmental timing of cerebellar defect not defined
  7. 2008 High

    Demonstrating that childhood absence epilepsy–associated signal peptide mutations (P11S, S15F, G32R) cause aberrant N-glycosylation and reduced GABA currents established the first molecular mechanism linking GABRB3 variants to receptor dysfunction.

    Evidence In vitro translation/translocation with canine microsomes, whole-cell patch-clamp in HEK293T cells

    PMID:18514161

    Open questions at the time
    • Whether hyperglycosylation itself causes ER retention or is a bystander not resolved
    • Neuronal context not tested
  8. 2012 High

    Detailed analysis of G32R revealed that it shifts receptor stoichiometry (reducing γ2L surface expression while increasing β3), shortens mean open time, and disrupts subunit-interface salt bridges, demonstrating that a single mutation can simultaneously alter assembly, trafficking, and gating.

    Evidence Surface biotinylation, whole-cell and single-channel electrophysiology, glycosylation mutagenesis, and homology modeling in HEK293T cells

    PMID:22303015

    Open questions at the time
    • Structural model based on homology rather than cryo-EM of mutant receptor
    • Synaptic consequences of altered stoichiometry not tested
  9. 2016 Medium

    Discovery that Gabrb3 deletion causes near-complete retinal depigmentation through cis-downregulation of Oca2 mRNA revealed an unexpected transcriptional regulatory relationship within the 15q11-13 locus beyond GABAA receptor function.

    Evidence Electron microscopy of melanosomes, exome and RNA sequencing in Gabrb3−/− mice

    PMID:28009282

    Open questions at the time
    • Mechanism linking GABRB3 loss to Oca2 downregulation not identified
    • Whether this is a direct or indirect regulatory effect is unknown
    • Relevance to human pigmentation phenotypes not established
  10. 2016 High

    Electrophysiology in sex-stratified Gabrb3 maternal-deletion mice showed that the mutation selectively enlarges mGluR1/5 responses and accelerates firing in male but not female cerebellar nuclear neurons, establishing sex-specific physiological consequences of GABRB3 haploinsufficiency.

    Evidence Whole-cell and cell-attached patch-clamp in cerebellar nuclear neurons from Gabrb3 m−/p+ mice, separated by sex

    PMID:27077953

    Open questions at the time
    • Molecular basis for sex-dependent compensation unknown
    • Whether sex differences extend to cortical circuits not tested
  11. 2017 High

    Electrophysiological testing of multiple mutations in coupling junctions and pore regions demonstrated that GABRB3 variants can cause either gain-of-function (uncoupled gating, rearranged hydrogen bonds) or loss-of-function (pore reshaping, low-conductance states), establishing bidirectional pathogenicity.

    Evidence Whole-cell patch-clamp and MD simulations for Cys-loop, M2-M3 loop, and pore mutations; oocyte voltage-clamp for 7 additional variants

    PMID:28053010 PMID:29162865

    Open questions at the time
    • In vivo consequences of gain-of-function not tested
    • Structural simulations not validated by experimental structures
  12. 2019 High

    Showing that disease-severity–correlated mutations reduce postsynaptic clustering of wild-type γ2 subunits in cortical neurons established that β3 is required for inhibitory synapse organization, not just channel function, and that dominant-negative effects on synapse assembly explain genotype–phenotype correlations.

    Evidence Flow cytometry, confocal microscopy, electrophysiology in HEK293T cells and rat cortical neurons; immunohistochemistry in Gabrb3+/− mice

    PMID:31435640

    Open questions at the time
    • Mechanism by which β3 mutations impair γ2 clustering not defined at molecular level
    • Whether synapse loss is developmental or ongoing not determined
  13. 2022 High

    Systematic classification of 44 pathogenic variants into gain-of-function and loss-of-function groups, with gain-of-function linked to more severe encephalopathy and loss-of-function to febrile seizures, established a genotype-to-phenotype framework with direct therapeutic implications.

    Evidence Electrophysiology in heterologous systems for 44 variants; multi-center clinical cohort genotype–phenotype analysis

    PMID:35383156

    Open questions at the time
    • Whether gain-of-function and loss-of-function require different therapeutic strategies not experimentally tested
    • Neuronal confirmation for all 44 variants lacking
  14. 2022 High

    Cell-type-specific Gabrb3 deletion from contralaterally projecting somatosensory pyramidal neurons revealed that β3-mediated inhibition is required for GABAergic synapse development, and its loss increases local synchrony and long-range functional connectivity, providing a circuit-level mechanism for cortical hyperexcitability.

    Evidence In vivo two-photon and widefield calcium imaging, conditional KO, synaptic immunostaining in developing mice

    PMID:36446382

    Open questions at the time
    • Whether circuit hyperconnectivity persists into adulthood not shown
    • Contribution to seizure generation versus behavioral phenotypes not separated
  15. 2022 Medium

    Endothelial-specific Gabrb3 deletion causing reduced vessel density, hypertension, and behavioral deficits revealed an unexpected non-neuronal role for GABRB3 in vascular development and blood pressure regulation.

    Evidence Endothelial conditional KO, laser Doppler/blood flow measurement, cardiac histology, behavioral battery

    PMID:35318369

    Open questions at the time
    • GABA signaling mechanism in endothelial cells not characterized
    • Whether vascular phenotype contributes to behavioral deficits independently of neuronal loss not resolved
    • Single lab finding not independently replicated
  16. 2024 High

    Sub-classifying gain-of-function variants by desensitization properties showed that reduced desensitization (transmembrane/pore variants) correlates with the most severe phenotypes including EIMFS and mortality, while accelerated decay (coupling-loop variants) partially limits gain-of-function, refining the mechanistic framework for prognosis.

    Evidence Two-electrode voltage-clamp in oocytes and whole-cell electrophysiology in mammalian cells for 20 gain-of-function variants with clinical correlation

    PMID:37647766

    Open questions at the time
    • Whether desensitization differences predict drug response not tested
    • Structural basis for desensitization changes not experimentally resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of gain-of-function gating changes at atomic resolution, the mechanism by which β3 mutations dominantly impair γ2 synaptic clustering, the signaling pathway mediating endothelial GABRB3 function, and the cis-regulatory mechanism linking GABRB3 to OCA2 expression within the 15q11-13 domain.
  • No cryo-EM structures of disease-mutant β3-containing receptors
  • Endothelial GABA signaling pathway undefined
  • Mechanism of GABRB3-OCA2 transcriptional coupling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 9 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-392499 Metabolism of proteins 2
Partners
GABRA1GABRA5GABRG2MECP2
Complex memberships
GABAA receptor (α1β3γ2)GABAA receptor (α5β3γ2)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The GABRB3 gene has a strong promoter element between alternative exons (exon 1 and exon 1a), binds Sp1 and at least one other nuclear factor at a site overlapping transcriptional start sites, and produces alternative transcripts with variant signal sequences whose relative levels vary between fetal and adult brain and between brain regions. Promoter activity assays, nuclear factor binding/footprinting, transcript analysis in cell lines and brain tissue The Journal of biological chemistry High 8382702
1995 A 50–60 kb domain between GABRB3 and GABRA5 undergoes allele-specific replication: maternal chromosome 15 replicates early in S phase while the paternal homologue replicates late; uniparental disomy or hemizygous deletion alters this kinetics, indicating reciprocal imprints regulate replication timing in this domain. Replication timing assay (BrdU incorporation, FISH) with uniparental disomy and deletion cell lines Nature genetics High 7795644
1999 Homozygous disruption of the gabrb3 gene in mice produces spontaneous seizures, EEG abnormalities, and behavioral characteristics resembling Angelman syndrome, directly demonstrating that loss of the GABAA receptor β3 subunit is sufficient to cause epileptogenesis. Gene knockout mouse model with EEG recording and behavioral analysis Epilepsy research High 10515160
2004 MeCP2 deficiency causes significantly reduced GABRB3 protein expression in postnatal brain, as shown in two Mecp2-deficient mouse strains and human Rett, Angelman, and autism brain samples, implicating MeCP2 as a transcriptional regulator of GABRB3. Quantitative immunoblot, laser scanning cytometry-based quantitative immunofluorescence and in situ hybridization on tissue microarrays Human molecular genetics High 15615769
2006 A disease-associated GABRB3 promoter haplotype (haplotype 2) has significantly lower transcriptional activity than the control haplotype; a T→C SNP within the exon 1a promoter reduces binding of the neuron-specific transcriptional activator N-Oct-3, explaining reduced GABRB3 expression in childhood absence epilepsy patients. Reporter gene assay in NT2 cells, electrophoretic mobility shift assay (EMSA), in silico transcription factor binding analysis Human molecular genetics High 16835263
2007 Gabrb3 knockout mice exhibit deficits in sociability, social novelty, nesting, exploratory behavior, and non-selective attention (reduced rearing), and display hypoplasia of cerebellar vermal lobules, establishing a role for GABRB3 in social behavior and cerebellar development. Behavioral battery (sociability, social novelty, nesting, rearing, open field) and semi-quantitative morphometry of cerebellar vermis in Gabrb3−/− mice Behavioural brain research High 17983671
2006 Gabrb3 gene disruption leads to enlargement of the pericoerulear dendritic zone of the locus coeruleus, hypotonia (poor wire-hanging performance), and increased risk-assessment behavior, indicating GABRB3 contributes to noradrenergic dendrite development and muscle tone regulation. Morphometric analysis of locus coeruleus, wire-hanging task, behavioral tests in Gabrb3−/− mice Brain research Medium 17156762
2008 GABRB3 missense mutations P11S, S15F, and G32R associated with childhood absence epilepsy cause hyperglycosylation of the β3 subunit N-terminus in an in vitro translation/translocation system and reduce whole-cell GABA-evoked current density when expressed as α1β3γ2S receptors in HEK293T cells. In vitro translation/translocation with canine microsomes (Western blot), whole-cell patch-clamp in HEK293T cells with rapid agonist application American journal of human genetics High 18514161
2009 The GABRB3 signal peptide variant P11S reduces whole-cell GABA-evoked current and decreases β3 subunit surface expression due to impaired intracellular processing, when expressed in α1β3γ2 or α3β3γ2 GABAA receptors; maternal but not paternal transmission of this variant is associated with autism. Whole-cell patch-clamp electrophysiology, cell-surface biotinylation/Western blot in transfected cells Molecular psychiatry High 19935738
2010 Gabrb3 heterozygous mice show parent-of-origin-dependent differences in tactile and heat hypersensitivity, sensorimotor competence, and prepulse inhibition, with associated differences in Gabrb3 expression in the reticular thalamic nucleus and bed nucleus of stria terminalis, indicating GABRB3 regulates somatosensory and sensorimotor processing in a region- and parent-of-origin-specific manner. Behavioral tests (von Frey filaments, hot plate, rotarod, PPI), quantitative Gabrb3 expression in brain subregions in heterozygous KO mice Behavioural brain research Medium 20699105
2012 The GABRB3 mutation G32R reduces surface expression of γ2L subunits and increases surface expression of β3 subunits (shifting receptor composition toward binary αβ3 and homomeric β3 receptors), increases N-glycosylation at Asn-33 via introduction of a basic residue at position 32, impairs channel gating (shorter mean open time), and reduces macroscopic current density in α1β3γ2L receptors; homology modeling indicates disrupted salt bridges at subunit interfaces. HEK293T cell surface expression (biotinylation/Western blot), whole-cell and single-channel patch-clamp, glycosylation site mutagenesis, homology modeling The Journal of biological chemistry High 22303015
2012 Common SNPs in the GABRB3 exon 1A promoter region increase luciferase reporter activity; the C allele of rs20317 creates binding motifs for cMYB and EGR-3 and significantly increases promoter activity; a REST binding site in a longer construct suppresses GABRB3 exon 1A transcription in non-neuronal contexts, indicating epigenetic regulation of GABRB3 variant 2 expression by REST. Luciferase reporter assay in HEK293 cells with deletion and SNP constructs Epilepsia Medium 22765836
2017 Seven GABRB3 mutations tested by two-electrode voltage-clamp in Xenopus oocytes (coexpressing mutant β3 with α5 and γ2s subunits) show that 5 of 7 mutations reduce GABA-induced current amplitudes or GABA sensitivity, establishing loss of receptor function as a disease mechanism across a broad spectrum of epilepsy phenotypes. Automated two-electrode voltage-clamp in Xenopus laevis oocytes Neurology High 28053010
2017 GABRB3 mutations in the Cys-loop (L170R) and M2-M3 loop (A305V) coupling junction cause gain-of-function by rearranging hydrogen bonds and uncoupling during activation, while the pore mutation T288N causes loss-of-function by reshaping the pore cavity and favoring low-conductance states with differential diazepam sensitivity; structural simulations support these mechanisms. Whole-cell patch-clamp electrophysiology in transfected cells, MD structural simulations Scientific reports High 29162865
2019 GABRB3 mutations N328D (Lennox-Gastaut syndrome) and E357K (juvenile absence epilepsy) both reduce total subunit expression in cortical neurons, reduce β3 and γ2 surface expression, and impair postsynaptic clustering of wild-type γ2 subunits at inhibitory synapses; N328D shows greater reductions than E357K, correlating with greater clinical severity; Gabrb3+/− mice also show reduced synaptic γ2 clustering. Flow cytometry (surface expression), patch-clamp electrophysiology, confocal microscopy, immunoblotting in HEK293T cells and rat cortical neurons; Gabrb3+/− mouse immunohistochemistry Brain : a journal of neurology High 31435640
2020 GABRB3 variants p.Glu77Lys and p.Thr287Ile cause a gain-of-function by increasing GABA potency (without changing maximum open-channel probability, deactivation kinetics, or absolute currents), leading to increased chloride flux at low GABA concentrations that mediate tonic currents; this explains clinical hypersensitivity to vigabatrin in patients carrying these variants. Two-electrode voltage-clamp electrophysiology in Xenopus oocytes using concatenated synaptic/extrasynaptic GABAA receptor constructs; receptor activation modeling Brain communications High 33585817
2022 44 pathogenic GABRB3 missense variants segregate into gain-of-function and loss-of-function groups by electrophysiological characterization; gain-of-function variants are associated with younger seizure onset, more severe intellectual disability, focal seizures, and hypotonia, while febrile seizures at onset are exclusive to the loss-of-function group, establishing that increased GABAergic activity via GABRB3 GoF causes more severe encephalopathy. Electrophysiology (GABA dose-response, current amplitude) in heterologous expression systems for 44 variants; clinical cohort genotype-phenotype analysis Nature communications High 35383156
2022 Gabrb3 is enriched in contralaterally projecting pyramidal neurons in the somatosensory cortex; conditional Gabrb3 ablation in vivo causes a developmental decrease in GABAergic synapses, increased local network synchrony, and long-lasting enhancement of functional connectivity specifically in contralateral pyramidal neuron subtypes, as well as increased cortical response to tactile stimulation at neonatal stages. In vivo two-photon and widefield calcium imaging in developing mice, cell-type-specific conditional KO, synaptic immunostaining Neuron High 36446382
2022 Selective deletion of Gabrb3 from endothelial cells (Gabrb3ECKO) reduces cortical and cardiac vessel density, increases cortical red blood cell velocity and blood flow, causes hypertension, and produces behavioral deficits (impaired social interaction, communication, anxiety, depression, reduced short-term memory, altered prepulse inhibition), establishing a non-neuronal role for GABRB3 in vascular development and function. Endothelial cell-specific conditional KO, laser Doppler/blood flow measurement, cardiac histology, behavioral battery Scientific reports Medium 35318369
2024 Among 20 gain-of-function GABRB3 variants, 7 reduce receptor desensitization at equilibrium (worsening gain-of-function, clustering in transmembrane/pore regions, correlating with earlier seizure onset and movement disorders/EIMFS/higher mortality) while 6 accelerate current decay kinetics (limiting gain-of-function, clustering in coupling loops, correlating with slightly milder phenotypes); reduced desensitization variants are associated with greater clinical severity. Two-electrode voltage-clamp electrophysiology in Xenopus oocytes and whole-cell electrophysiology in transfected mammalian cells for 20 variants Brain : a journal of neurology High 37647766
2025 The GABRB3 p.Met80Val variant causes a 2.6-fold increase in β3 protein expression with predominantly cytoplasmic localization, increased current amplitude and GABA sensitivity, and reduced zinc sensitivity in α1β3γ2 receptors, indicating a gain-of-function mechanism that involves altered receptor conformation or zinc-binding site disruption. Fluorescence microscopy (subcellular localization), Western blot (protein expression), whole-cell patch-clamp electrophysiology in transfected cells, structural modeling Italian journal of pediatrics Medium 40542409
2016 Deletion of Gabrb3 alone in mice causes nearly complete loss of retinal pigmentation due to atrophied melanosomes; Oca2 mRNA and other genes adjacent to Gabrb3 are substantially reduced in Gabrb3−/− mice despite intact Oca2 coding sequence, indicating GABRB3 loss downregulates OCA2 through complex transcriptional regulation in the 15q11-13 region. Electron microscopy (melanosome morphology), exome and RNA sequencing, Gabrb3−/− mouse model Cell reports Medium 28009282
2016 In wild-type mice, cerebellar nuclear (CbN) cells show sex differences in synaptic excitation (mGluR1/5-dependent currents), inhibitory IPSC kinetics, and spontaneous firing rates. The Gabrb3 maternal deletion (m−/p+) mutation selectively enlarges mGluR1/5 responses and accelerates spontaneous firing in male but not female CbN cells, while IPSC kinetics are unchanged, demonstrating that sex-specific cerebellar physiology produces distinct responses to Gabrb3 mutation. Whole-cell and cell-attached patch-clamp recordings in cerebellar nuclear neurons from Gabrb3 m−/p+ mice, separated by sex eLife High 27077953

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Human molecular genetics 299 15615769
2002 Association between a GABRB3 polymorphism and autism. Molecular psychiatry 228 11920158
2007 Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder. Behavioural brain research 171 17983671
2010 Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3. PloS one 130 20808828
2008 Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy. American journal of human genetics 128 18514161
1999 Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium. American journal of medical genetics 115 10490705
2017 Mutations in GABRB3: From febrile seizures to epileptic encephalopathies. Neurology 86 28053010
1993 A strong promoter element is located between alternative exons of a gene encoding the human gamma-aminobutyric acid-type A receptor beta 3 subunit (GABRB3). The Journal of biological chemistry 86 8382702
2009 Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Molecular psychiatry 83 19935738
2010 Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3. Behavioural brain research 78 20699105
2006 A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity. Human molecular genetics 78 16835263
2019 Synaptic clustering differences due to different GABRB3 mutations cause variable epilepsy syndromes. Brain : a journal of neurology 76 31435640
2022 Molecular and clinical descriptions of patients with GABAA receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation. Epilepsia 67 35718920
2022 Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies. Nature communications 66 35383156
2003 Angelman syndrome reviewed from a neurophysiological perspective. The UBE3A-GABRB3 hypothesis. Neuropediatrics 61 12973656
2015 GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy. Developmental medicine and child neurology 55 26645412
1995 Domain organization of allele-specific replication within the GABRB3 gene cluster requires a biparental 15q11-13 contribution. Nature genetics 54 7795644
2001 Linkage disequilibrium between GABRB3 gene and nonsyndromic familial cleft lip with or without cleft palate. Human genetics 53 11810291
2012 GABRB3 mutation, G32R, associated with childhood absence epilepsy alters α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor expression and channel gating. The Journal of biological chemistry 50 22303015
1999 Possible association between childhood absence epilepsy and the gene encoding GABRB3. Biological psychiatry 50 10509183
1999 GABA and epileptogenesis: comparing gabrb3 gene-deficient mice with Angelman syndrome in man. Epilepsy research 50 10515160
2014 Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders. Molecular autism 48 24999380
2007 Association of GABRB3 polymorphisms with autism spectrum disorders in Korean trios. Neuropsychobiology 45 17230033
1997 Structure and organization of GABRB3 and GABRA5. Genomics 42 9126483
2013 Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism. Molecular autism 39 24321478
2016 Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice. eLife 37 27077953
2012 Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children. Molecular autism 35 22769427
2009 Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features. Schizophrenia research 33 19268543
2020 Gain-of-function GABRB3 variants identified in vigabatrin-hypersensitive epileptic encephalopathies. Brain communications 30 33585817
2019 Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation. Epilepsia 30 31755996
2017 GABA A Receptor Coupling Junction and Pore GABRB3 Mutations are Linked to Early-Onset Epileptic Encephalopathy. Scientific reports 28 29162865
2022 Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex. Neuron 24 36446382
2017 A mutation in GABRB3 associated with Dravet syndrome. American journal of medical genetics. Part A 24 28544625
2014 Evidence for linkage and association of GABRB3 and GABRA5 to panic disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 22 24755890
2010 Screening of GABRB3 in French-Canadian families with idiopathic generalized epilepsy. Epilepsia 21 20550555
2012 Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia. Psychiatry research 20 22414661
2006 Gabrb3 gene deficient mice exhibit increased risk assessment behavior, hypotonia and expansion of the plexus of locus coeruleus dendrites. Brain research 20 17156762
2016 Beyond Epilepsy and Autism: Disruption of GABRB3 Causes Ocular Hypopigmentation. Cell reports 15 28009282
2018 Meta-analysis of GABRB3 Gene Polymorphisms and Susceptibility to Autism Spectrum Disorder. Journal of molecular neuroscience : MN 14 30074174
2012 Effects on promoter activity of common SNPs in 5' region of GABRB3 exon 1A. Epilepsia 14 22765836
2007 Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy. Epilepsy research 14 17215107
2017 Early onset epileptic encephalopathy with a novel GABRB3 mutation treated effectively with clonazepam: A case report. Medicine 13 29390378
2018 Neonatal Onset of Epilepsy of Infancy with Migrating Focal Seizures Associated with a Novel GABRB3 Variant in Monozygotic Twins. Neuropediatrics 12 29444535
2012 Visualization of the spatial positioning of the SNRPN, UBE3A, and GABRB3 genes in the normal human nucleus by three-color 3D fluorescence in situ hybridization. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 12 22801776
1997 Lack of association between juvenile myoclonic epilepsy and GABRA5 and GABRB3 genes. American journal of medical genetics 12 9129713
2023 Association of GABRG3, GABRB3, HTR2A gene variants with autism spectrum disorder. Gene 11 37019319
2020 A novel GABRB3 variant in Dravet syndrome: Case report and literature review. Molecular genetics & genomic medicine 11 32945607
2022 Gabrb3 endothelial cell-specific knockout mice display abnormal blood flow, hypertension, and behavioral dysfunction. Scientific reports 10 35318369
2014 Genetic analysis of GABRB3 at 15q12 as a candidate gene of schizophrenia. Psychiatric genetics 10 24865167
2014 Association analysis of GABRB3 promoter variants with heroin dependence. PloS one 10 25025424
2004 Case-control study and transmission/disequilibrium tests of the genes encoding GABRA5 and GABRB3 in a Chinese population affected by childhood absence epilepsy. Chinese medical journal 10 15498372
2024 Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity. Brain : a journal of neurology 9 37647766
2008 Association of the GABRB3 gene with nonsyndromic oral clefts. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 8 18452349
2013 Paradoxical worsening of seizure activity with pregabalin in an adult with isodicentric 15 (IDIC-15) syndrome involving duplications of the GABRB3, GABRA5 and GABRG3 genes. BMC neurology 7 23663378
2017 The GABRB3 Polymorphism and its Association with Schizophrenia. Journal of molecular neuroscience : MN 6 29196882
2013 Polymorphisms in GABRB3 and oral clefting in the Brazilian population. DNA and cell biology 6 23438326
2019 Cleft Palate as Distinguishing Feature in a Patient with GABRB3 Epileptic Encephalopathy. Neuropediatrics 5 31319422
2007 [Molecular analysis of the GABRB3 gene in autistic patients: an exploratory study]. Investigacion clinica 5 17598645
2021 Phenotype Expression Variability in Children with GABRB3 Heterozygous Mutations. Oman medical journal 4 33854792
2021 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. BMC medical genomics 2 34530807
2019 Functional analysis of haplotypes and promoter activity at the 5' region of the human GABRB3 gene and associations with schizophrenia. Molecular genetics & genomic medicine 2 30908890
2004 Physical mapping of the pink-eyed dilution complex in mouse chromosome 7 shows that Atp10c is the only transcript between Gabrb3 and Ube3a. DNA sequence : the journal of DNA sequencing and mapping 2 15620220
2024 Integrated analysis identifies GABRB3 as a biomarker in prostate cancer. BMC medical genomics 1 38287309
2021 High Mobility Group Box 1/Toll-like Receptor 4 Signaling Increases GABRB3 Expression in Alcohol Exposure. Neuropsychiatric disease and treatment 1 34103917
2012 [Polymorphisms of rs4906902 and rs8179184 loci in the promoter of the GABRB3 gene and their relevance with schizophrenia]. Fa yi xue za zhi 1 22812221
2002 [Evaluation of q11-q13 locus of chromosome 15 aberrations and polymorphisms in the B3 subunit of the GABA-A receptor gene (GABRB3) in autistic patients]. Psychiatria polska 1 12491987
1993 [The GABAA receptor beta 3-subunit gene (GABRB3) as a candidate responsible for central nerve disturbances in Angelman syndrome (AS)]. Nihon rinsho. Japanese journal of clinical medicine 1 8411721
2026 Predictive value of seizure onset for gross motor dysfunction in individuals with pathogenic GABRB2 and GABRB3 variants. Epilepsia 0 41603155
2026 GABRB3 Gene Polymorphisms Influences the Analgesic Response to Acupuncture Treatment in Patients With Chronic Knee Pain: A Randomized Controlled Neuroimaging Transcriptomics Study. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41999225
2025 Clinical and functional characterization of the GABRB3 p.Met80Val variant in early-onset epilepsy with long-term follow-up. Italian journal of pediatrics 0 40542409
2025 A GABRB3 mutation (c.5G>A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report. Experimental and therapeutic medicine 0 41019480