Affinage

GABRA2

Gamma-aminobutyric acid receptor subunit alpha-2 · UniProt P47869

Length
451 aa
Mass
51.3 kDa
Annotated
2026-04-28
72 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GABRA2 encodes the α2 subunit of the GABAA receptor, a ligand-gated chloride channel central to inhibitory neurotransmission, drug response, and neurodevelopment. The gene is transcribed from multiple alternative promoters generating diverse mRNA isoforms whose expression varies across brain regions and developmental stages, with haplotypic variation and H3K9me3 epigenetic marks regulating promoter activity (PMID:15950776, PMID:12354299, PMID:34970138). α2-containing GABAA receptors are required for the anxiolytic actions of benzodiazepines and barbiturates, modulate acute ethanol sensitivity through specific residues (H101, Q241, S270/L277), and facilitate psychostimulant-driven conditioned reinforcement; a hypomorphic intronic variant that halves α2 expression acts as a genetic modifier of epilepsy severity in Dravet and SCN8A encephalopathy models, rescuable by CRISPR correction (PMID:18313124, PMID:27717041, PMID:34086081, PMID:33140451). De novo missense variants in the transmembrane domain cause developmental and epileptic encephalopathy through gain-of-function (tonic channel opening, p.T292K) or loss-of-function (reduced expression, impaired pentameric assembly with GABRB3/GABRG2, p.A308V) mechanisms (PMID:29961870, PMID:39737842).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 High

    Establishing that Gabra2 uses multiple alternative promoters and first exons to generate diverse 5′-UTR isoforms during brain development answered how α2 subunit expression is tuned across developmental stages and brain regions.

    Evidence RT-PCR, genomic sequencing, and promoter characterization in rat brain across developmental stages

    PMID:12354299

    Open questions at the time
    • Human promoter architecture not yet characterized at this point
    • No link to specific transcription factor regulation
    • Functional consequences of individual isoforms on receptor assembly not tested
  2. 2005 High

    Demonstration that the human GABRA2 gene likewise uses alternative promoters and splicing, with haplotypic variation altering promoter activity, established a molecular basis for how non-coding genetic variants modulate GABRA2 expression and linked this to addiction-associated alleles.

    Evidence RT-PCR, DNA sequencing, and transient transfection promoter assays in human brain tissue; parallel human pharmacogenetic alcohol challenge study

    PMID:15702134 PMID:15950776

    Open questions at the time
    • Which transcription factors bind differentially to risk haplotypes unknown
    • Precise cell-type-level expression effects of haplotypes not resolved
  3. 2008 High

    Gabra2 knockout mice losing both benzodiazepine and barbiturate anxiolytic responses established that α2-containing GABAA receptors are the obligate mediators of anxiolysis for both drug classes, not just benzodiazepines.

    Evidence Genetic knockout with conditioned emotional response behavioral pharmacology in mice

    PMID:18313124

    Open questions at the time
    • Molecular mechanism by which α2 subunit selectively confers anxiolytic sensitivity unclear
    • Circuit-level locus of anxiolytic action not identified
  4. 2012 High

    Showing that α2 knockout increases sensitivity to ethanol's motor-impairing effects without changing blood ethanol levels or self-administration revealed that α2-containing receptors normally protect against acute ethanol-induced sedation and ataxia.

    Evidence Rotarod, loss-of-righting-reflex, blood alcohol concentration, and operant self-administration in Gabra2 KO vs WT mice

    PMID:23115637

    Open questions at the time
    • Specific receptor subtype composition (α2βxγx) mediating ethanol sensitivity not defined
    • Whether compensatory upregulation of other subunits contributes to phenotype not examined
  5. 2015 Medium

    Multiple convergent findings established broader roles: rs279858*C allele reduces GABRA2 expression in human iPSC-derived neurons in a developmental window; α2 KO abolishes methylphenidate-facilitated conditioned reinforcement; and gabra2 knockdown in zebrafish disrupts neural proliferation and proneural gene expression, indicating roles beyond mature synaptic inhibition.

    Evidence Human iPSC qPCR/RNA-seq genotype-stratified analysis; mouse KO operant behavior; zebrafish morpholino knockdown with proliferation/apoptosis/gene expression assays

    PMID:26250693 PMID:26635556 PMID:29124181

    Open questions at the time
    • Developmental signaling role in mammalian neurogenesis not confirmed with genetic models
    • iPSC expression effect not replicated in adult brain—developmental specificity vs technical limitation unclear
    • Morpholino off-target effects not excluded by genetic mutant
  6. 2015 Medium

    H3K9me3 enrichment at the Gabra2 promoter and its sensitivity to SUV39H1 inhibition identified an epigenetic layer of Gabra2 transcriptional regulation that operates in an age-dependent manner.

    Evidence ChIP for H3K9me3 at Gabra2 promoter, qPCR, and ETP69 pharmacological inhibition in young and aged mice

    PMID:34970138

    Open questions at the time
    • Causal relationship between H3K9me3 and Gabra2 expression not established by genetic manipulation of the mark
    • Cell-type specificity of epigenetic regulation not resolved
  7. 2016 High

    Point-mutation knockin mice revealed that individual α2 residues control distinct facets of alcohol behavior—H101R escalates binge drinking, Q241M blunts chronic intake, S270H/L277A prevents abstinence-induced social deficits—decomposing the receptor's pharmacological interfaces into separable behavioral outputs.

    Evidence Multiple knockin lines assessed with drinking-in-the-dark, continuous access, intermittent access, and social approach paradigms

    PMID:27717041

    Open questions at the time
    • Electrophysiological consequences of each knockin mutation on receptor function in vivo not measured
    • Whether these residues act via allosteric modulation or direct ethanol binding not distinguished
  8. 2018 High

    Identification of a de novo p.T292K variant that produces tonically open channels with reduced expression in vitro established the first gain-of-function disease mechanism for GABRA2, linking it to developmental and epileptic encephalopathy.

    Evidence Whole-cell patch-clamp in HEK293T cells expressing mutant α2β3γ2 receptors

    PMID:29961870

    Open questions at the time
    • In vivo confirmation of tonic opening in neuronal context not performed
    • Whether tonic current causes excitotoxicity or shunting inhibition defect not resolved
  9. 2020 High

    FRMD7 was identified as a direct binding partner of the α2 intracellular TM3–TM4 loop, with mutations disrupting binding and causing GABAA receptor mislocalization, revealing a trafficking/anchoring partner for α2-containing receptors relevant to infantile nystagmus syndrome.

    Evidence GST pull-down, co-immunoprecipitation, and C. elegans FRAP/locomotion rescue assays

    PMID:32446246

    Open questions at the time
    • Whether FRMD7 interaction is specific to α2 vs other GABAA α subunits not tested
    • Mammalian in vivo validation of receptor mislocalization upon FRMD7 loss not shown
  10. 2020 High

    CRISPR correction of a hypomorphic intronic indel in Gabra2 (C57BL/6J) that halves α2 expression rescued seizure severity and survival in both Scn1a and Scn8a encephalopathy models, causally validating Gabra2 as a genetic modifier of epilepsy through regulation of inhibitory synaptic receptor abundance.

    Evidence QTL mapping, quantitative Western blot, CRISPR/Cas9 allele correction, seizure/survival phenotyping in Scn1a+/− and Scn8a mutant mice

    PMID:33140451 PMID:34086081

    Open questions at the time
    • Whether the modifier effect extends to other genetic epilepsies not tested
    • Specific synaptic vs extrasynaptic receptor populations affected not distinguished
  11. 2021 High

    Correction of the same Gabra2 intronic variant reduced methamphetamine-induced locomotor sensitization, extending the gene's modifier role beyond epilepsy to psychostimulant behavioral responses and confirming the causal QTL variant.

    Evidence Genome-wide QTL analysis, cis-eQTL mapping in striatum, CRISPR allele correction, methamphetamine locomotor assay

    PMID:34677900

    Open questions at the time
    • Downstream circuit mechanism linking reduced α2 expression to enhanced psychostimulant sensitivity unclear
    • Whether dopaminergic or GABAergic neurons are the critical cell type not resolved
  12. 2024 Medium

    A novel p.A308V variant was shown to reduce α2 protein expression and impair co-immunoprecipitation with GABRB3 and GABRG2, establishing a loss-of-function mechanism through disrupted pentameric subunit assembly distinct from the gain-of-function tonic opening mechanism.

    Evidence Western blotting, co-immunoprecipitation, and immunofluorescence in transfected HEK293T cells

    PMID:39737842

    Open questions at the time
    • Electrophysiological characterization of p.A308V not performed
    • Assembly defect not confirmed in neurons or brain tissue
    • Only one variant tested—generalizability to other extracellular-domain mutations unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for how individual α2 residues differentially transduce benzodiazepine, neurosteroid, and ethanol modulation into distinct behavioral outputs, and which neuronal populations and synaptic vs extrasynaptic receptor pools mediate each pharmacological phenotype, remain unresolved.
  • No high-resolution structure of the α2-containing receptor with drug ligands
  • Cell-type-specific conditional knockouts not yet reported
  • Developmental vs adult contributions of α2 to circuit function not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 2 R-HSA-382551 Transport of small molecules 2
Partners
FRMD7GABRB3GABRG2
Complex memberships
GABAA receptor (α2βγ pentamer)

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 A de novo missense variant in GABRA2 (p.T292K) reduces channel expression and produces mutant GABA-A receptor channels that are tonically open even in the absence of GABA, as demonstrated by whole-cell patch-clamp recordings in HEK293T cells expressing the mutant α2 subunit with β and γ subunits. Whole-cell patch-clamp electrophysiology in HEK293T cells expressing mutant GABRA2 constructs Brain : a journal of neurology High 29961870
2005 The human GABRA2 gene produces multiple mRNA isoforms through alternative splicing and alternative promoter use; at least four major isoforms arise from combinations of two alternative 5' and 3' exons, and two functional promoters drive differential expression in brain regions. Naturally occurring haplotypes differ in promoter activity, indicating that non-coding variants regulate GABRA2 expression. RT-PCR, DNA sequencing, and transient transfection promoter activity assays in human brain tissue samples Brain research. Molecular brain research High 15950776
2002 The rat Gabra2 gene has three alternative first exons, each with its own functional promoter, generating six mRNA isoforms that differ in their 5'-UTRs; differential activation of these alternative promoters is used during brain development, and the 5'-UTR diversity affects GABA-A receptor expression levels. RT-PCR, genomic sequencing, promoter characterization in rat brain, and expression analysis across developmental stages Journal of neurochemistry High 12354299
2008 Targeted deletion of the GABRA2 gene (α2 subunit knockout) in mice abolishes the anxiolytic effects of both benzodiazepines (diazepam) and barbiturates (pentobarbital) in the conditioned emotional response test, demonstrating that α2-containing GABA-A receptors mediate anxiolytic actions of both drug classes. Genetic knockout (GABRA2 deletion) with behavioral pharmacology (conditioned emotional response, anxiolytic drug challenge) in mice Pharmacology, biochemistry, and behavior High 18313124
2012 Deletion of the Gabra2 gene (α2 subunit knockout) in mice increases hypersensitivity to the acute sedative and ataxic effects of ethanol (shorter latency to fall on Rotarod, prolonged loss of righting reflex) without altering blood ethanol concentrations or ethanol self-administration, indicating a protective role for α2-containing GABA-A receptors against acute ethanol-induced motor impairment. Genetic knockout with Rotarod/wire hang behavioral assay, loss-of-righting-reflex test, blood alcohol concentration measurement, and operant ethanol self-administration in mice PloS one High 23115637
2016 Point mutations in Gabra2 affecting specific amino acid residues modulate distinct aspects of alcohol drinking behavior in mice: the H101R mutation (BZD-insensitive) escalates binge-like drinking; the Q241M mutation (neurosteroid-insensitive) blunts chronic ethanol intake; and S270H/L277A mutations (high-ethanol-insensitive) prevent forced-abstinence-induced social deficits, demonstrating residue-specific roles of α2-containing GABA-A receptors in alcohol-related behaviors. Point mutation knockin mice assessed with drinking in the dark, continuous access, and intermittent access alcohol drinking protocols, plus social approach testing Alcoholism, clinical and experimental research High 27717041
2021 A B6-specific single nucleotide deletion within an intron of Gabra2 reduces mRNA and protein expression by ~50% and lowers the abundance of α2-containing GABA-A receptors in hippocampal synapses; CRISPR/Cas9 correction of this deletion restores expression and rescues epilepsy phenotypes in Scn1a+/- (Dravet syndrome model) mice, validating Gabra2 as a genetic modifier of Dravet syndrome severity. Quantitative Western blot and receptor abundance measurement, CRISPR/Cas9 knock-in correction, seizure and survival phenotyping in Scn1a+/- mice Mammalian genome : official journal of the International Mammalian Genome Society High 34086081
2020 The same hypomorphic intronic deletion in Gabra2 (C57BL/6J strain) that reduces α2 subunit expression is associated with earlier seizure onset and shortened lifespan in Scn8a gain-of-function mutant mice; correction of the splice site variant restores transcript abundance, delays seizure onset, and extends survival, confirming Gabra2 as a modifier of SCN8A encephalopathy severity. QTL mapping, knock-in allele correction, RT-PCR transcript quantification, and survival/seizure onset phenotyping in Scn8a mutant mice Epilepsia High 33140451
2021 A quantitative trait variant consisting of a functional intronic indel in Gabra2 underlies increased methamphetamine-induced locomotor sensitivity in mice; CRISPR/Cas9 correction of the mutant deletion on the C57BL/6J background to the wild-type allele was sufficient to reduce methamphetamine-induced locomotor activity, validating this variant as the causal quantitative trait variant. Genome-wide QTL analysis, cis-eQTL mapping in striatum, CRISPR/Cas9 allele correction, and methamphetamine locomotor activity assay Genes, brain, and behavior High 34677900
2020 FRMD7 directly interacts with the intracellular loop between transmembrane domains 3 and 4 of the GABRA2 protein (a domain critical for receptor transport and localization), as shown by GST pull-down and co-immunoprecipitation; FRMD7 mutations associated with infantile nystagmus syndrome reduce this binding, and loss of the FRMD7 homologue frm-3 in C. elegans impairs GABA-A receptor localization (assessed by FRAP) and locomotion. GST pull-down, co-immunoprecipitation, western blotting, immunofluorescence localization, and C. elegans FRAP/locomotion rescue assays Investigative ophthalmology & visual science High 32446246
2015 The alcohol-dependence-associated GABRA2 rs279858*C allele is associated with significantly lower GABRA2 mRNA levels in human iPSC-derived neural cell cultures, and expression of the entire chromosome 4p12 GABA-A subunit gene cluster (GABRG1, GABRA2, GABRA4, GABRB1) is correlated and co-regulated, with the C-allele defining a low-expression cluster. This effect was not observed in postmortem adult cortex, suggesting a developmental window for the genotypic effect on expression. qPCR and RNA sequencing in human iPSC-derived neural cell lines stratified by genotype; comparison with postmortem brain datasets Alcoholism, clinical and experimental research Medium 26250693
2015 In mice, exercise increases Gabra2 mRNA expression in aged animals while decreasing it in young animals, and inhibition of the H3K9me3 methyltransferase SUV39H1 (ETP69 treatment) also reduces Gabra2 expression in young mice, suggesting that H3K9me3 at the Gabra2 promoter region is a repressive epigenetic regulator of Gabra2 transcription in an age-dependent manner. Chromatin immunoprecipitation (H3K9me3 at Gabra2 promoter), qPCR for mRNA, pharmacological inhibition (ETP69) in young and aged mice Frontiers in aging neuroscience Medium 34970138
2015 In mice, loss of GABRA2 (α2-subunit knockout) abolishes the ability of methylphenidate to facilitate conditioned reinforcement for stimuli associated with reward, mirroring the blunted motivational/reinforcing effects of methylphenidate seen in humans carrying GABRA2 addiction-risk SNPs, suggesting that α2-containing GABA-A receptors are required for psychostimulant-mediated enhancement of conditioned reinforcement circuits. α2 knockout mouse operant conditioned reinforcement paradigm combined with human pharmacogenetic study of methylphenidate subjective effects Frontiers in behavioral neuroscience Medium 26635556
2015 In zebrafish, gabra2 morpholino knockdown disrupts the pattern of neural proliferation and increases apoptosis in the mid- and hindbrain; it also alters expression of signaling pathway genes (notch1, pax2, fgf8, wnt1), downregulates the proneural gene neuroD, and reduces gad1b (GAD67) expression, indicating that gabra2 participates in CNS developmental signaling pathways regulating proliferation and neurogenesis. Morpholino knockdown in zebrafish embryos with proliferation markers, apoptosis assay, and gene expression analysis (qPCR/in situ hybridization) Biochemistry and biophysics reports Medium 29124181
2005 GABRA2 alleles (rs279858) modulate the subjective effects of alcohol in humans; individuals homozygous for the common A-allele experienced greater subjective alcohol effects than G-allele carriers, and finasteride (a 5α-reductase inhibitor that blocks neuroactive steroid synthesis) reduced subjective effects selectively in A-allele homozygotes, providing indirect evidence that neuroactive steroids mediate some subjective effects of alcohol through GABRA2-containing receptors. Randomized double-blind placebo-controlled human laboratory alcohol challenge with finasteride pretreatment, genotype-stratified analysis Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Medium 15702134
2024 A novel de novo GABRA2 missense variant (p.Ala308Val) in the extracellular domain reduces protein expression, impairs co-immunoprecipitation interactions with GABRB3 and GABRG2 subunits (suggesting destabilization of the pentameric receptor complex), but does not affect subcellular localization of the mutant α2 protein in transfected cells. Western blotting, co-immunoprecipitation, and immunofluorescence in transfected HEK293T cells with structural modeling Annals of clinical and translational neurology Medium 39737842
2020 Structural analysis of seven pathogenic missense variants in GABRA2 associated with early infantile epileptic encephalopathy showed that all variants localize to the transmembrane domain—near the desensitization gate, activation gate, or inter-subunit interfaces—positions equivalent to known pathogenic mutations in other Cys-loop receptors, indicating that disruption of these conserved structural elements underlies channel dysfunction. Protein structural modeling and comparative analysis with known pathogenic positions in other Cys-loop receptors; novel variant identified by trio whole-genome sequencing Molecular genetics & genomic medicine Low 32347641

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. American journal of human genetics 498 15024690
2004 Allelic and haplotypic association of GABRA2 with alcohol dependence. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 231 15274050
2006 The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages. Behavior genetics 169 16557364
2006 Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatric genetics 144 16395124
2006 Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample. Behavior genetics 127 16622805
2007 GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence. Journal of psychiatric research 123 17207817
2005 GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 121 15702134
2009 Role of GABRA2 in trajectories of externalizing behavior across development and evidence of moderation by parental monitoring. Archives of general psychiatry 104 19487630
2011 Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Molecular psychiatry 102 21483437
2010 The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence. Biological psychiatry 100 19833324
2006 Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 88 16874763
2018 De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy. Brain : a journal of neurology 83 29961870
2006 Marital status, alcohol dependence, and GABRA2: evidence for gene-environment correlation and interaction. Journal of studies on alcohol 82 16562401
2013 Association of gamma-aminobutyric acid A receptor α2 gene (GABRA2) with alcohol use disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 78 24136292
2007 Markers in the 5'-region of GABRG1 associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent GABRA2 gene. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 76 17507911
2008 GABRG1 and GABRA2 as independent predictors for alcoholism in two populations. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 75 18818659
2007 Variation in GABRA2 predicts drinking behavior in project MATCH subjects. Alcoholism, clinical and experimental research 68 17949392
2010 Role of GABRA2 in moderating subjective responses to alcohol. Alcoholism, clinical and experimental research 51 21118274
2010 A polymorphism in GABRA2 is associated with the medial frontal response to alcohol cues in an fMRI study. Alcoholism, clinical and experimental research 50 20698837
2008 Targeted deletion of the GABRA2 gene encoding alpha2-subunits of GABA(A) receptors facilitates performance of a conditioned emotional response, and abolishes anxiolytic effects of benzodiazepines and barbiturates. Pharmacology, biochemistry, and behavior 46 18313124
2008 The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample. Alcoholism, clinical and experimental research 46 18727688
2013 How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity. Twin research and human genetics : the official journal of the International Society for Twin Studies 42 23561058
2012 GABRA2 markers moderate the subjective effects of alcohol. Addiction biology 42 22501025
2013 Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood. Addiction biology 37 23692184
2007 The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity: within-family association and linkage analyses. Journal of studies on alcohol and drugs 37 17690794
2011 GABRG1 and GABRA2 variation associated with alcohol dependence in African Americans. Alcoholism, clinical and experimental research 33 21919924
2013 A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration. Alcohol and alcoholism (Oxford, Oxfordshire) 31 24166645
2015 GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures. Alcoholism, clinical and experimental research 30 26250693
2005 Alternative splicing and promoter use in the human GABRA2 gene. Brain research. Molecular brain research 29 15950776
2013 Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2. Behavior genetics 27 23974430
2017 A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 26 29422393
2011 Genetic association study of GABRA2 single nucleotide polymorphisms and electroencephalography in alcohol dependence. Neuroscience letters 26 21683760
2015 Role of gabra2, GABAA receptor alpha-2 subunit, in CNS development. Biochemistry and biophysics reports 24 29124181
2012 Gamma-aminobutyric acid A receptor, α-2 (GABRA2) variants as individual markers for alcoholism: a meta-analysis. Psychiatric genetics 22 22555154
2021 Gabra2 is a genetic modifier of Dravet syndrome in mice. Mammalian genome : official journal of the International Mammalian Genome Society 21 34086081
2015 Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele. Development and psychopathology 21 25797587
2014 Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse. Journal of child psychology and psychiatry, and allied disciplines 21 24811113
2020 Gabra2 is a genetic modifier of Scn8a encephalopathy in the mouse. Epilepsia 20 33140451
2015 Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking. Alcoholism, clinical and experimental research 20 26087834
2009 Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems, controls and available first degree relatives. Drug and alcohol dependence 20 19783384
2017 Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 19 28237505
2012 Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration. PloS one 19 23115637
2007 Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4. Genomics 19 17976953
2008 Effects of GABRA2 variation on physiological, psychomotor and subjective responses in the alcohol challenge twin study. Twin research and human genetics : the official journal of the International Society for Twin Studies 18 18361719
2014 Genetic variation in GABRA2 moderates peer influence on externalizing behavior in adolescents. Brain and behavior 16 25365806
2010 GABRA2 and alcohol use disorders: no evidence of an association in an Italian case-control study. Alcoholism, clinical and experimental research 16 20102561
2018 PROSPER Intervention Effects on Adolescents' Alcohol Misuse Vary by GABRA2 Genotype and Age. Prevention science : the official journal of the Society for Prevention Research 14 28185103
2018 GABRA2, alcohol, and illicit drug use: An event-level model of genetic risk for polysubstance use. Journal of abnormal psychology 14 29528673
2015 Association of GABAA receptor α2 subunit gene (GABRA2) with alcohol dependence-related aggressive behavior. Progress in neuro-psychopharmacology & biological psychiatry 11 26116794
2014 Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study. Behavior genetics 11 24687270
2016 Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice. Alcoholism, clinical and experimental research 10 27717041
2020 Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate. Molecular genetics & genomic medicine 9 32347641
2020 FRMD7 Mutations Disrupt the Interaction with GABRA2 and May Result in Infantile Nystagmus Syndrome. Investigative ophthalmology & visual science 9 32446246
2017 GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose-Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers. Alcoholism, clinical and experimental research 9 29131352
2016 Beyond risk: Prospective effects of GABA Receptor Subunit Alpha-2 (GABRA2) × Positive Peer Involvement on adolescent behavior. Development and psychopathology 9 27581089
2021 Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner. Frontiers in aging neuroscience 8 34970138
2018 Sex and β-Endorphin Influence the Effects of Ethanol on Limbic Gabra2 Expression in a Mouse Binge Drinking Model. Frontiers in genetics 8 30555510
2002 The 5'-flanking region of the rat GABA(A) receptor alpha2-subunit gene (Gabra2). Journal of neurochemistry 8 12354299
2021 A quantitative trait variant in Gabra2 underlies increased methamphetamine stimulant sensitivity. Genes, brain, and behavior 7 34677900
2015 Mechanisms in the relation between GABRA2 and adolescent externalizing problems. European child & adolescent psychiatry 6 25804982
1999 A sequence-ready BAC contig of the GABAA receptor gene cluster Gabrg1-Gabra2-Gabrb1 on mouse chromosome 5. Genome research 6 10447508
2017 A GABRA2 polymorphism improves a model for prediction of drinking initiation. Alcohol (Fayetteville, N.Y.) 5 28847377
2015 Motivational Effects of Methylphenidate are Associated with GABRA2 Variants Conferring Addiction Risk. Frontiers in behavioral neuroscience 5 26635556
2021 The Effects of Gene Variations of GABRA2, GABRB1, GABRG2, GAD1 and SLC1A3 on Patients with Propofol During Anesthesia Induction. Pharmacogenomics and personalized medicine 4 34557020
2021 Correction of the hypomorphic Gabra2 splice site variant in mouse strain C57BL/6J modifies the severity of Scn8a encephalopathy. HGG advances 4 35047853
2025 GABRA2-related encephalopathy: Identification of two phenotypes with distinctive electroclinical features. Epilepsia 2 40528577
2022 CYP2A6 and GABRA2 Gene Polymorphisms are Associated With Dexmedetomidine Drug Response. Frontiers in pharmacology 2 35873555
2018 Developmental Change in Adolescent Delinquency: Modeling Time-Varying Effects of a Preventative Intervention and GABRA2 Halpotype Linked to Alcohol Use. Journal of youth and adolescence 2 30244312
2024 5,7,3',4',5'-Pentamethoxyflavone, a Flavonoid Monomer Extracted From Murraya paniculata (L.) Jack, Alleviates Anxiety Through the A2AR/Gephyrin/GABRA2 Pathway. Phytotherapy research : PTR 0 39261011
2024 A novel de novo GABRA2 gene missense variant causing developmental epileptic encephalopathy in a Chinese patient. Annals of clinical and translational neurology 0 39737842
2022 Prospective DNA Methylation Analysis of the CpG GABRA2 Receptor Subunit in Alcohol Dependence during Detoxification. Medicina (Kaunas, Lithuania) 0 36422192
2018 Romantic Partner Alcohol Misuse Interacts with GABRA2 Genotype to Predict Frequency of Drunkenness in Young Adulthood. Journal of contemporary criminal justice 0 31598057