Affinage

GABRB3

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

Length
473 aa
Mass
54.1 kDa
Annotated
2026-06-09
71 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GABRB3 encodes the β3 subunit of GABAA receptors and is a critical determinant of inhibitory chloride-channel assembly, surface trafficking, and synaptic function; in developing cortex it is required for GABAergic synapse formation and the functional integration of interhemispheric pyramidal neuron circuits (PMID:36446382), and in endothelial cells it is required for normal cerebral and cardiac vascular development (PMID:35318369). The β3 subunit assembles with α and γ2 subunits into ternary receptors, and its proper maturation governs the surface expression and synaptic clustering of the partnering γ2 subunit, so that mutant β3 consistently lowers γ2 surface expression and impairs postsynaptic GABAA receptor clustering at inhibitory synapses (PMID:31435640). Pathogenic missense variants partition into two mechanistic classes: loss-of-function variants reduce GABA-evoked currents, GABA sensitivity, or surface receptor expression—often through impaired ER-to-surface maturation, abnormal glycosylation, or altered subunit oligomerization—and produce milder epilepsy syndromes (PMID:18514161, PMID:22303015, PMID:28053010), whereas gain-of-function variants increase GABA potency or reduce receptor desensitization and produce more severe developmental and epileptic encephalopathy, demonstrating the paradox that enhanced GABAergic activity yields worse clinical outcomes (PMID:33585817, PMID:35383156, PMID:37647766). GABRB3 transcription is controlled through dual exon-1/exon-1a promoters bound by Sp1 and the neuron-specific activator N-Oct-3, repressed in non-neuronal contexts by REST, and disease-associated promoter SNPs reduce N-Oct-3 binding and transcriptional output (PMID:8382702, PMID:16835263, PMID:22765836); postnatal β3 protein levels additionally depend on MeCP2 (PMID:15615769). The gene lies within the imprinted 15q11-13 domain, exhibits parent-of-origin allele-specific replication timing, and its loss perturbs expression of neighbouring genes including Oca2 (PMID:7795644, PMID:28009282).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 Medium

    Establishing how GABRB3 transcription is initiated answered whether the gene uses simple or complex regulatory architecture, revealing dual alternative promoters with differential developmental and regional activity.

    Evidence Promoter reporter assays and EMSA identifying Sp1 binding plus characterization of alternative exon-1/exon-1a transcripts

    PMID:8382702

    Open questions at the time
    • The second nuclear factor binding the pyrimidine-rich region was unidentified
    • Functional consequence of the alternative signal sequences for receptor maturation was not tested
  2. 1995 Medium

    Mapping allele-specific replication timing across the GABRB3/GABRA5 region established that the locus is subject to genomic imprinting on chromosome 15, a context relevant to parent-of-origin disease effects.

    Evidence Replication timing assays (BrdU/FISH) in cells with uniparental disomy or chromosome 15 deletion

    PMID:7795644

    Open questions at the time
    • Did not establish whether GABRB3 itself is monoallelically expressed
    • Mechanistic link between replication timing and transcription not defined
  3. 1997 High

    Defining the full genomic structure provided the exon/intron framework needed to interpret subsequent disease mutations.

    Evidence Physical mapping with P1/lambda/PAC contigs and exon/intron boundary sequencing

    PMID:9126483

    Open questions at the time
    • Structural map alone does not address function or regulation
  4. 2004 High

    Linking MeCP2 to GABRB3 answered why neurodevelopmental disorders converge on reduced β3, showing MeCP2 regulates β3 protein levels in postnatal brain.

    Evidence Quantitative immunoblot, immunofluorescence, TaqMan PCR and in situ hybridization in two Mecp2-deficient mouse strains and human Rett/Angelman/autism brain

    PMID:15615769

    Open questions at the time
    • Direct versus indirect MeCP2 regulation of the GABRB3 promoter not resolved
    • Functional consequence for inhibitory transmission not measured
  5. 2006 High

    Characterizing a CAE-associated promoter haplotype answered how non-coding variation lowers GABRB3 expression, identifying reduced N-Oct-3 binding as the cause.

    Evidence Luciferase reporter assays in NT2 cells and EMSA at the polymorphic exon-1a promoter site

    PMID:16835263

    Open questions at the time
    • In vivo brain expression effect of the haplotype not shown
    • Causal contribution to epilepsy at organismal level not established
  6. 2012 Medium

    Dissection of the exon-1A core promoter and REST repression clarified how GABRB3 is restricted to neuronal contexts and how regulatory SNPs modulate expression.

    Evidence Luciferase deletion-construct assays in HEK293 cells with in silico motif analysis (REST, cMYB, EGR-3)

    PMID:22765836

    Open questions at the time
    • TF binding (REST, cMYB, EGR-3) inferred in silico, not biochemically confirmed for all sites
    • Neuronal-cell validation limited
  7. 2009 High

    Mechanistic studies of N-terminal/signal-peptide variants established a loss-of-function route in which impaired intracellular processing reduces surface β3 and GABA current.

    Evidence In vitro translation/translocation with microsomes, whole-cell electrophysiology, and surface biotinylation in heterologous cells for P11S/S15F/G32R

    PMID:18514161 PMID:19935738

    Open questions at the time
    • Maternal-transmission autism association is genetic, not mechanistic
    • Synaptic-level consequences in neurons not tested in these studies
  8. 2012 High

    Detailed analysis of G32R showed a single basic-residue substitution simultaneously shifts subunit stoichiometry away from ternary receptors and impairs channel gating, linking oligomerization defects to loss-of-function.

    Evidence Surface biotinylation, tunicamycin glycosylation blockade, whole-cell and single-channel patch-clamp, and homology modeling in HEK293T cells

    PMID:22303015

    Open questions at the time
    • Salt-bridge model of oligomerization not validated by structure
    • Effect in native neuronal receptors not measured
  9. 2017 High

    Systematic electrophysiology established that most epilepsy-associated GABRB3 mutations reduce receptor function, framing GABAergic disinhibition as a dominant disease mechanism, while structural mapping defined gain- versus loss-of-function residue classes.

    Evidence Two-electrode voltage clamp in Xenopus oocytes for 7 mutations, plus electrophysiology and structural simulation of EOEE variants

    PMID:28053010 PMID:29162865

    Open questions at the time
    • Oocyte currents may not fully reflect native synaptic receptors
    • Genotype-phenotype assignment for individual residues incomplete
  10. 2019 High

    Demonstrating that mutant β3 consistently lowers γ2 surface expression answered how diverse β3 variants converge on a common synaptic deficit—impaired postsynaptic GABAA receptor clustering.

    Evidence Flow cytometry, patch-clamp, confocal imaging and immunoblot in HEK293T cells and cortical neurons, validated in Gabrb3+/- mice

    PMID:31435640

    Open questions at the time
    • Molecular basis of the differential cellular mechanisms (N328D vs E357K) not fully resolved
    • In vivo circuit consequence not measured here
  11. 2016 High

    Mouse models of Gabrb3 deficiency revealed roles beyond synaptic inhibition, including sex-specific cerebellar physiology changes and pigmentation defects via downregulation of neighbouring 15q11-13 genes.

    Evidence Whole-cell recordings in cerebellar nuclei of maternal-deficient mice; Gabrb3 knockout with electron microscopy and RNA-seq

    PMID:27077953 PMID:28009282

    Open questions at the time
    • Mechanism by which Gabrb3 loss downregulates adjacent genes (Oca2) is unresolved
    • Sex-specific effects not mechanistically explained
  12. 2022 High

    In vivo and large-scale functional studies established the bidirectional disease logic of GABRB3: a developmental requirement in cortical and vascular circuits, and a counterintuitive correlation in which gain-of-function variants cause more severe encephalopathy.

    Evidence Cell-type-specific calcium imaging and conditional knockouts in cortex and endothelium; electrophysiological classification of 44 variants with clinical correlation

    PMID:35318369 PMID:35383156 PMID:36446382

    Open questions at the time
    • How endothelial GABAA signaling drives angiogenesis is undefined
    • Cellular basis for severe phenotypes of gain-of-function variants not fully mechanistic
  13. 2024 High

    Resolving desensitization as a separate variable refined the gain-of-function class, showing pore-region variants that reduce desensitization worsen disease while coupling-loop variants that accelerate decay are milder.

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

    PMID:37647766

    Open questions at the time
    • Structural basis of desensitization changes not directly determined
    • Therapeutic implications of desensitization tuning untested
  14. 2025 Medium

    Characterization of M80V illustrated a mixed mechanism combining increased but cytoplasmically retained protein with heightened GABA sensitivity and reduced zinc inhibition.

    Evidence Western blot, fluorescence microscopy, whole-cell patch-clamp and structural modeling

    PMID:40542409

    Open questions at the time
    • Zinc-binding-site change inferred from modeling, not structurally confirmed
    • In vivo phenotypic correlation limited to a case

Open questions

Synthesis pass · forward-looking unresolved questions
  • How endothelial Gabrb3-mediated GABAA signaling mechanistically controls vascular development, and how β3 loss propagates to downregulate neighbouring imprinted 15q11-13 genes, remain unresolved.
  • No molecular pathway linking endothelial GABAA signaling to angiogenesis
  • No mechanism for cross-gene transcriptional effects within 15q11-13
  • HMGB1/TLR4 regulation of Gabrb3 shown only pharmacologically without pathway reconstitution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0005198 structural molecule activity 2 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 2
Partners
GABRA1GABRA5GABRG2
Complex memberships
GABAA receptor

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The GABRB3 gene contains a strong promoter element located between alternative exons (exon 1 and exon 1a). Transcription initiates from multiple sites within a pyrimidine-rich region that binds Sp1 and at least one other unidentified nuclear factor. Alternative exons produce variant transcripts with different signal sequences, with relative levels varying between fetal and adult brain and between brain regions. Promoter reporter assays, nuclear factor binding (gel shift/EMSA), characterization of alternative transcripts by RNA analysis The Journal of biological chemistry Medium 8382702
1995 A 50–60 kb domain of allele-specific replication exists between the GABRB3 and GABRA5 genes: the maternal chromosome 15 replicates this domain in early S phase, while the paternal homologue replicates it in late S phase. Uniparental disomy or hemizygous deletion of chromosome 15 alters these allele-specific replication kinetics, indicating that the domain is regulated by reciprocal imprints on maternal and paternal chromosomes. Replication timing assays (BrdU incorporation/FISH) in cells with uniparental disomy or deletion of chromosome 15 Nature genetics Medium 7795644
1997 GABRB3 spans approximately 250 kb of DNA and is organized into 9 exons ranging from 68 to 504 bp. Exon/intron borders were fully characterized, and a reference STR marker (155CA-2) was positioned ≥60 kb beyond the 3′ terminus of GABRB3, while D15S97 lies within intron 4. Physical mapping using P1, lambda phage, and PAC clone contigs; sequencing of exon/intron boundaries Genomics High 9126483
2004 MECP2 deficiency causes significantly reduced protein expression of the GABRB3-encoded β3 GABAA receptor subunit in postnatal brain. Reduced GABRB3 expression was demonstrated in two Mecp2-deficient mouse strains and in human Rett, Angelman, and autism brain samples, indicating that MeCP2 regulates GABRB3 expression in the postnatal mammalian brain. Quantitative immunoblot, automated immunofluorescence quantitation by laser scanning cytometry on tissue microarrays, TaqMan PCR, in situ hybridization Human molecular genetics High 15615769
2006 A CAE-associated GABRB3 promoter haplotype (haplotype 2) contains a T-to-C SNP that reduces binding of the neuron-specific transcriptional activator N-Oct-3 to the exon 1a promoter, resulting in significantly lower transcriptional activity compared to the control haplotype 1 promoter. EMSA demonstrated reduced nuclear protein binding affinity at this polymorphic site. Reporter gene assays (luciferase) in NT2 cells, electrophoretic mobility shift assay (EMSA), in silico transcription factor binding analysis Human molecular genetics High 16835263
2008 GABRB3 missense mutations P11S, S15F, and G32R (located in the signal peptide/exon 1a and exon 2 N-terminal region) cause hyperglycosylation of the β3 subunit in an in vitro translation/translocation system with canine microsomes. When expressed in HEK293T cells as α1β3γ2S receptors, each mutation reduced GABA-evoked whole-cell current density, consistent with impaired receptor maturation and trafficking from ER to cell surface. In vitro translation and translocation system with canine microsomes (Western blot for glycosylation), whole-cell patch-clamp electrophysiology in HEK293T cells (rapid agonist application), expression in HeLa cells American journal of human genetics High 18514161
2009 The GABRB3 signal peptide variant P11S reduces whole-cell GABA-activated current and decreases β3 subunit protein on the cell surface due to impaired intracellular β3 subunit processing, demonstrated in α1β3γ2 and α3β3γ2 GABAA receptor combinations. Maternal (but not paternal) transmission of the variant is associated with autism. Whole-cell electrophysiology, cell-surface protein quantification (biotinylation/Western blot), intracellular processing assays in heterologous expression systems Molecular psychiatry High 19935738
2012 The CAE-linked GABRB3 G32R mutation has three mechanistic effects: (1) it shifts the subunit composition of surface receptors from ternary αβ3γ2L toward binary αβ3 and homomeric β3 receptors (reducing surface γ2L expression); (2) it increases N-glycosylation at Asn-33 (the adjacent glycosylation site), though glycosylation changes are not responsible for altered surface expression—rather, both effects stem from the basic residue at position 32; (3) α1β3(G32R)γ2L receptors exhibit impaired channel gating with shorter mean open time on single-channel recording. Homology modeling shows the mutation alters salt bridges at subunit interfaces important for oligomerization. Surface biotinylation/Western blot, tunicamycin glycosylation blockade, whole-cell patch-clamp, single-channel recording, homology modeling in HEK293T cells The Journal of biological chemistry High 22303015
2012 A core promoter element for GABRB3 exon 1A is located 230 bp upstream of exon 1A; deletion of this region abolishes luciferase reporter activity. The REST (RE1-silencing transcription factor) binding site in longer constructs suppresses GABRB3 exon 1A expression in non-neuronal contexts. SNP rs20317 allele C creates binding motifs for cMYB and EGR-3 and significantly increases luciferase expression activity compared to allele G. Luciferase reporter assay with deletion constructs in HEK293 cells, in silico transcription factor motif analysis Epilepsia Medium 22765836
2017 Electrophysiological analysis of 7 GABRB3 mutations in Xenopus laevis oocytes (coexpressing mutant β3 with α5 and γ2s subunits using automated two-electrode voltage clamp) revealed that 5 of 7 mutations reduce GABA-induced current amplitudes or GABA sensitivity, establishing reduced receptor function/GABAergic disinhibition as the disease mechanism for most epilepsy-associated GABRB3 mutations. Two-electrode voltage-clamp electrophysiology in Xenopus oocytes with wild-type or mutant β3 plus α5 and γ2s subunits Neurology High 28053010
2017 Three de novo GABRB3 mutations linked to early-onset epileptic encephalopathy (EOEE) affect conserved structural domains: Cys-loop/M2-M3 coupling junction mutations (L170R, A305V) cause gain-of-function by uncoupling receptor activation and forming new hydrogen bonds in the open state, while the M2 pore mutation (T288N) reshapes the pore cavity, favors low-conductance receptors, and causes loss-of-function with differential diazepam sensitivity. Electrophysiology in heterologous cells, structural simulation/homology modeling, patch-clamp recordings Scientific reports Medium 29162865
2019 Multiple GABRB3 mutations differentially reduce surface expression of mutant β3 subunits; however, surface expression of the partnering γ2 subunit is consistently lower when co-expressed with any mutant β3 compared to wild-type β3. Because γ2 subunits are critical for synaptic GABAA receptor clustering, this impairs postsynaptic clustering of GABAA receptors at inhibitory synapses. Two specific mutations (N328D associated with Lennox-Gastaut syndrome; E357K associated with juvenile absence epilepsy) both reduce total subunit expression in cortical neurons and impair synaptic clustering of γ2 subunits by different cellular mechanisms, with N328D causing greater reduction. Wild-type γ2 subunits were also reduced and less clustered at inhibitory synapses in Gabrb3+/- mice. High-throughput flow cytometry, patch-clamp electrophysiology in HEK293T cells and rodent cortical neurons, confocal microscopy, immunoblotting, Gabrb3+/- mouse model Brain : a journal of neurology High 31435640
2019 Screening of 1,320 compounds identified vinpocetine as enhancing GABRB3 channel conductance in cell models expressing the Y302C GABRB3 mutation (Lennox-Gastaut syndrome). Vinpocetine administration resulted in dose-dependent reduction in spike-wave discharge frequency on EEG in the patient, suggesting direct pharmacological rescue of the mutant GABAA receptor channel. Electrophysiological compound screening in cell models, clinical EEG monitoring Epilepsia Low 31755996
2020 GABRB3 variants p.Glu77Lys and p.Thr287Ile exhibit gain-of-function characterized by increased potency of GABA (leftward shift in concentration-response curve) without change in estimated maximum open channel probability, deactivation kinetics, or absolute currents, when expressed in concatenated synaptic and extrasynaptic GABAA receptor constructs. Modeling indicates these variants increase chloride flux in response to low GABA concentrations that mediate tonic currents, explaining clinical hypersensitivity to vigabatrin. Two-electrode voltage-clamp electrophysiology in Xenopus oocytes with concatenated receptor constructs, receptor activation modeling Brain communications High 33585817
2022 Pathogenic GABRB3 missense variants segregate into gain-of-function (increased GABAergic activity) and loss-of-function (decreased GABAergic activity) groups, with electrophysiological characterization of 44 variants. Gain-of-function variants are associated with more severe developmental and epileptic encephalopathy, paradoxically showing that increased GABAergic activity produces worse outcomes. Loss-of-function variants are associated with milder epilepsy syndromes including febrile seizures at onset. Electrophysiological classification of 44 GABRB3 variants, multi-center clinical correlation Nature communications High 35383156
2022 Gabrb3 is enriched in contralaterally projecting pyramidal neurons of the somatosensory cortex. Gabrb3 ablation leads to a developmental decrease in GABAergic synapses, increased local network synchrony, long-lasting enhancement in functional connectivity specifically of contralateral (not ipsilateral) pyramidal neuron subtypes, and increased cortical response to tactile stimulation at neonatal stages, demonstrating a required role for Gabrb3 in inhibitory function and the functional integration of pyramidal neuron subtypes during circuit assembly. In vivo two-photon and widefield calcium imaging in developing mice, cell-type-specific conditional knockout, synaptic quantification Neuron High 36446382
2022 Endothelial cell-specific deletion of Gabrb3 (Gabrb3ECKO) results in a reduction in vessel densities and abnormal vessel morphology in the telencephalon persisting into the adult neocortex, increased red blood cell velocity and cortical blood flow, reduced vessel densities in the heart, and cardiac hypertensive changes, demonstrating that Gabrb3-mediated GABAA signaling in endothelial cells is required for normal vascular development in brain and heart. Endothelial-specific conditional knockout mouse model, cortical blood flow measurement (red blood cell velocity), cardiac histology, vessel density quantification Scientific reports Medium 35318369
2024 Among 20 gain-of-function GABRB3 variant receptors, 13 alter receptor desensitization properties in addition to GABA sensitivity. Seven variants reduce desensitization at equilibrium (worsening gain-of-function) and are clustered in transmembrane regions constituting the channel pore; these correlate with more severe clinical outcomes (earlier seizure onset, movement disorders, EIMFS). Six variants accelerate current decay kinetics (limiting gain-of-function) and are clustered in coupling loops; these correlate with somewhat milder phenotypes. Two-electrode voltage-clamp electrophysiology in Xenopus oocytes (current decay kinetics, steady-state currents), whole-cell electrophysiology in transfected mammalian cells for selected 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 most protein retained in the cytoplasm, and when incorporated into α1β3(M80V)γ2 receptors shows increased current amplitude, heightened GABA sensitivity, and reduced zinc sensitivity relative to wild-type receptors, consistent with altered receptor conformation or zinc-binding site affecting inhibition. Western blot (protein quantification), fluorescence microscopy (subcellular localization), whole-cell patch-clamp electrophysiology, structural modeling Italian journal of pediatrics Medium 40542409
2016 In Gabrb3 maternal heterozygous (m-/p+) mice modeling Angelman syndrome, CbN neurons show sex-specific responses: mutant males (but not females) exhibit enlarged mGluR1/5-dependent synaptic currents and accelerated spontaneous firing compared to wild-type, while IPSC kinetics are unchanged in both sexes. Wild-type males and females differ in baseline synaptic excitation, inhibition (Purkinje-mediated IPSC kinetics), and intrinsic firing properties, revealing that sex differences in cerebellar physiology provide distinct baselines for responses to the Gabrb3 mutation. Whole-cell patch-clamp recordings in cerebellar nuclei neurons of wild-type and Gabrb3 m-/p+ mice, separated by sex; rotarod behavioral testing eLife High 27077953
2016 Deletion of Gabrb3 alone in mice causes nearly complete loss of retinal pigmentation due to atrophied melanosomes (shown by electron microscopy), even though the Oca2 gene is intact. mRNA abundance of Oca2 and other genes adjacent to Gabrb3 is substantially reduced in Gabrb3-/- mice, suggesting that GABRB3 loss downregulates OCA2 expression through complex transcriptional regulation in the 15q11-13 region. Gabrb3 knockout mouse model, electron microscopy, exome sequencing, RNA sequencing, gene expression quantification Cell reports High 28009282
2021 HMGB1/TLR4 signaling upregulates Gabrb3 expression in alcohol-exposed mouse prefrontal cortex and striatum. Inhibition of HMGB1 decreased Gabrb3 transcript and protein levels as well as inflammatory cytokine (TNFα, IL-1β) levels in an intraperitoneal alcohol mouse model. Intraperitoneal alcohol mouse model, HMGB1 inhibitor treatment, quantitative RT-PCR, Western blot Neuropsychiatric disease and treatment Low 34103917

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 300 15615769
2002 Association between a GABRB3 polymorphism and autism. Molecular psychiatry 229 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 172 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 131 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 87 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
2006 A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity. Human molecular genetics 79 16835263
2019 Synaptic clustering differences due to different GABRB3 mutations cause variable epilepsy syndromes. Brain : a journal of neurology 78 31435640
2010 Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3. Behavioural brain research 78 20699105
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 72 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 69 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 49 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 38 27077953
2012 Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children. Molecular autism 36 22769427
2009 Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features. Schizophrenia research 33 19268543
2019 Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation. Epilepsia 32 31755996
2020 Gain-of-function GABRB3 variants identified in vigabatrin-hypersensitive epileptic encephalopathies. Brain communications 31 33585817
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 23 24755890
2010 Screening of GABRB3 in French-Canadian families with idiopathic generalized epilepsy. Epilepsia 21 20550555
2006 Gabrb3 gene deficient mice exhibit increased risk assessment behavior, hypotonia and expansion of the plexus of locus coeruleus dendrites. Brain research 21 17156762
2012 Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia. Psychiatry research 20 22414661
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
2023 Association of GABRG3, GABRB3, HTR2A gene variants with autism spectrum disorder. Gene 12 37019319
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
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

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