Affinage

GABRA2

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

Length
451 aa
Mass
51.3 kDa
Annotated
2026-06-09
72 papers in source corpus 17 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GABRA2 encodes the α2 subunit of the GABAA receptor, a pentameric ligand-gated chloride channel, and α2-containing receptors govern distinct facets of neuronal inhibition, drug response, and neurodevelopment (PMID:29961870, PMID:18313124). In assembled receptors the α2 subunit physically partners with β and γ subunits (GABRB3, GABRG2), and a de novo extracellular-domain variant (p.A308V) that weakens co-assembly with these subunits destabilizes the pentamer and reduces channel expression (PMID:39737842). De novo missense variants concentrate in the transmembrane domain near the activation and desensitization gates and inter-subunit interfaces, producing gain-of-function channels: the p.T292K variant yields receptors that open tonically in the absence of GABA, driving early-onset epileptic encephalopathy (PMID:29961870, PMID:32347641). Genetically, α2-containing receptors mediate the anxiolytic actions of benzodiazepines and barbiturates and shape responses to ethanol and psychostimulants; knockout mice lose benzodiazepine/barbiturate anxiolysis, show heightened acute ethanol sensitivity, and fail to support methylphenidate-facilitated conditioned reinforcement, while residue-specific knock-in mutations dissociate benzodiazepine-site, neurosteroid-site, and ethanol-sensitivity contributions to escalated alcohol drinking (PMID:18313124, PMID:23115637, PMID:27717041, PMID:26635556). GABRA2 expression is set by alternative 5′ promoters and splicing, by H3K9me3 marks at the promoter, and by β-endorphin signaling in limbic regions, and a hypomorphic intronic deletion that lowers synaptic α2 abundance acts as a genetic modifier of seizure severity and psychostimulant response, with CRISPR correction restoring expression and rescuing phenotypes (PMID:34086081, PMID:35047853, PMID:34677900, PMID:15950776, PMID:34970138, PMID:30555510). The α2 intracellular TM3–TM4 loop binds FRMD7, which regulates receptor transport/localization, and gabra2 knockdown in zebrafish perturbs CNS proliferation, apoptosis, and patterning gene expression, implicating the subunit in neurodevelopment beyond synaptic inhibition (PMID:32446246, PMID:29124181).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 Medium

    Established that Gabra2 transcription is governed by multiple alternative promoters and developmentally regulated 5′-exon usage, defining a layer of expression control independent of coding sequence.

    Evidence cDNA/genomic alignment, transcription start site mapping, and promoter functional characterization in rat with developmental expression analysis

    PMID:12354299

    Open questions at the time
    • Trans-acting factors driving the alternative promoters not identified
    • Functional consequence of each 5′-UTR isoform on translation not quantified
  2. 2005 High

    Extended promoter/splicing regulation to humans and linked it to natural genetic variation, showing haplotypes differ in promoter activity and thus could underlie GABRA2 disease associations.

    Evidence RT-PCR/sequencing of human brain mRNA plus transient transfection promoter assays with haplotype constructs

    PMID:15950776

    Open questions at the time
    • Causal haplotype variants not pinpointed
    • In vivo brain expression differences between haplotypes not measured
  3. 2008 High

    Answered which GABAA receptor subunit mediates benzodiazepine and barbiturate anxiolysis, assigning both to α2-containing receptors.

    Evidence α2 knockout mice in a conditioned emotional response task with diazepam and pentobarbital challenge

    PMID:18313124

    Open questions at the time
    • Specific brain circuits/cell types responsible not localized
    • Does not distinguish synaptic vs extrasynaptic α2 contribution
  4. 2012 High

    Determined α2's role in acute ethanol responses, showing it protects against sedative/ataxic effects without governing self-administration or ethanol metabolism.

    Evidence α2 KO mice with rotarod, loss-of-righting-reflex, blood ethanol, and operant self-administration assays

    PMID:23115637

    Open questions at the time
    • Mechanism by which α2 limits acute ethanol effects unresolved
    • Compensatory changes in other subunits in KO not excluded
  5. 2015 Medium

    Resolved how α2 circuits contribute to addiction vulnerability via conditioned reinforcement, with concordant mouse and human pharmacogenetic data on methylphenidate.

    Evidence α2 KO mice in conditioned-reinforcement task plus parallel human SNP × methylphenidate crossover study

    PMID:26635556

    Open questions at the time
    • Direction of causality between SNPs and behavior in humans correlational
    • Receptor-level mechanism not defined
  6. 2015 Medium

    Linked an alcohol-dependence risk allele (rs279858*C) to reduced GABRA2 expression in a developmental cell model and showed co-regulation with neighboring 4p12 GABAA subunit genes, while noting absence of the effect in adult cortex.

    Evidence iPSC-derived neural cultures from genotyped donors with qPCR/RNA-seq plus postmortem brain datasets

    PMID:26250693

    Open questions at the time
    • Developmental-stage dependence of the eQTL not mechanistically explained
    • Causal variant within the haplotype not isolated
  7. 2016 High

    Dissociated the benzodiazepine, neurosteroid, and ethanol-sensitivity sites on α2 in vivo, assigning each to specific residues controlling distinct alcohol-drinking phenotypes.

    Evidence Gabra2 point-mutant knock-in mice (H101R, Q241M, S270H/L277A) across multiple drinking and social paradigms with pharmacological rescue

    PMID:27717041

    Open questions at the time
    • Circuit-level loci of each pharmacological action not mapped
    • Translation to human polymorphic sites not established
  8. 2018 High

    Identified a gain-of-function disease mechanism, showing a de novo variant produces constitutively open channels causing early-onset epilepsy.

    Evidence Whole-cell patch-clamp of mutant α2/β/γ receptors expressed in HEK293T cells with mutagenesis (p.T292K)

    PMID:29961870

    Open questions at the time
    • In vivo neuronal consequences of tonic opening not modeled
    • Generality across other epilepsy variants not tested here
  9. 2018 Medium

    Connected β-endorphin signaling to sexually dimorphic limbic Gabra2 regulation during binge drinking, identifying an upstream neuropeptide modulator.

    Evidence Drinking-in-the-dark model in β-endorphin KO vs WT mice with regional qRT-PCR

    PMID:30555510

    Open questions at the time
    • Direct mechanism linking β-endorphin to Gabra2 transcription unknown
    • Behavioral relevance of the expression change not tested
  10. 2020 Medium

    Defined a physical regulator of α2 trafficking, showing FRMD7 binds the α2 intracellular loop and that disease mutations reduce binding and impair receptor mobility.

    Evidence GST pull-down, Co-IP, immunofluorescence, and FRAP in C. elegans frm-3 null with rescue

    PMID:32446246

    Open questions at the time
    • Mechanism of FRMD7-dependent transport not resolved
    • Mammalian validation of trafficking role pending
  11. 2020 Low

    Mapped pathogenic missense variants onto receptor structure, placing them near gates and inter-subunit interfaces and aligning with other Cys-loop epilepsy variants.

    Evidence Trio whole-genome sequencing with structural modeling and conservation analysis (no functional assay)

    PMID:32347641

    Open questions at the time
    • Computational only — no electrophysiology performed
    • Predicted gating effects of each variant unverified
  12. 2021 High

    Validated a hypomorphic intronic deletion as a causal genetic modifier of epilepsy by demonstrating CRISPR correction restores synaptic α2 and rescues seizure phenotypes.

    Evidence Quantitative receptor abundance measurement, CRISPR/Cas9 allele correction, and seizure/survival analysis in Scn1a+/− mice

    PMID:34086081 PMID:35047853

    Open questions at the time
    • Human relevance of the mouse-specific deletion uncertain
    • Mechanism by which the intronic indel reduces expression not fully detailed
  13. 2021 High

    Showed the same intronic variant is a quantitative trait variant for methamphetamine-induced locomotion, generalizing its functional impact to psychostimulant response.

    Evidence QTL mapping in Reduced Complexity Cross mice with cis-eQTL analysis and CRISPR correction plus locomotor assay

    PMID:34677900

    Open questions at the time
    • Circuit mediating altered stimulant sensitivity not identified
    • Relationship to human stimulant traits untested
  14. 2024 Medium

    Revealed a distinct disease mechanism for an extracellular-domain variant, showing impaired co-assembly with partner subunits without mislocalization.

    Evidence Trio whole-exome sequencing, structural modeling, Western blot, Co-IP with GABRB3/GABRG2, and immunofluorescence in HEK293T (p.A308V)

    PMID:39737842

    Open questions at the time
    • No electrophysiology to define channel functional consequence
    • Single Co-IP-based assembly assessment without quantitative stoichiometry

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how α2 subunit expression level, subcellular trafficking, and gating are integrated at native synapses to set inhibitory tone, and how the diverse human risk and pathogenic variants map onto specific circuit-level phenotypes.
  • No native-synapse functional model linking expression dosage to inhibition
  • Circuit-specific contributions of α2 to anxiety, addiction, and seizure phenotypes not dissected
  • Human FRMD7-GABRA2 trafficking axis not functionally validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0005215 transporter activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 2 R-HSA-1266738 Developmental Biology 1
Partners
FRMD7GABRB3GABRG2
Complex memberships
GABAA receptor

Evidence

Reading pass · 16 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 GABAA receptor channels that are tonically open even in the absence of GABA, establishing a gain-of-function mechanism contributing to early-onset epilepsy. Whole-cell patch-clamp electrophysiology in HEK293T cells expressing mutant α2/β/γ subunits; mutagenesis Brain High 29961870
2008 Targeted deletion of the GABRA2 gene (α2-subunit knockout mice) abolishes the anxiolytic effects of both benzodiazepines (diazepam) and barbiturates (pentobarbital) in a conditioned emotional response task, demonstrating that α2-containing GABAA receptors mediate anxiolytic effects of both drug classes and are involved in circuits underlying conditioned anxiety. Genetic knockout (α2 KO mice) with conditioned emotional response behavioral testing; pharmacological challenge with diazepam and pentobarbital Pharmacology, biochemistry, and behavior High 18313124
2012 Deletion of GABRA2 (α2-subunit KO 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, indicating a protective role for α2-subunits against acute ethanol effects; ethanol self-administration was unchanged in KO mice. Genetic knockout mice; rotarod, wire hang, and loss-of-righting-reflex assays; blood ethanol concentration measurement; operant ethanol self-administration PloS one High 23115637
2016 Point mutations in Gabra2 reveal distinct functional roles of specific residues: BZD-insensitive (H101R) α2-containing receptors lead to escalated binge-like drinking; Q241M substitution (blocking neuroactive steroid modulation) blunts chronic escalated alcohol intake; S270H/L277A substitution (reducing high-concentration ethanol sensitivity) results in excessive alcohol consumption and abolishes forced-abstinence-induced social deficits. Gabra2 point-mutant knockin mice; drinking-in-the-dark, continuous access, and intermittent access alcohol protocols; social approach assays; pharmacological rescue with allopregnanolone and midazolam Alcoholism, clinical and experimental research High 27717041
2021 A hypomorphic intronic deletion in Gabra2 in C57BL/6J mice reduces α2 subunit mRNA and protein by ~50% and lowers the abundance of α2-containing GABAA receptors in hippocampal synapses; CRISPR/Cas9 correction of this deletion restores Gabra2 expression, increases α2-containing receptor abundance at hippocampal synapses, and rescues epilepsy phenotypes (seizure onset and survival) in Scn1a+/− Dravet syndrome mice, validating Gabra2 as a genetic modifier of Dravet syndrome. Quantitative measurement of GABAA receptor subunit abundance; CRISPR/Cas9 allele correction; Scn1a+/− mouse model; seizure monitoring and survival analysis Mammalian genome High 34086081 35047853
2021 A functional intronic indel in Gabra2 on the C57BL/6J background underlies a QTL for methamphetamine-induced locomotor activity; CRISPR/Cas9 correction of this deletion reduces methamphetamine stimulant sensitivity, validating this variant as a quantitative trait variant (QTV) affecting psychostimulant response. Genome-wide QTL analysis in Reduced Complexity Cross mice; cis-eQTL mapping; CRISPR/Cas9 allele correction; locomotor activity assay after methamphetamine Genes, brain, and behavior High 34677900
2005 The human GABRA2 gene produces multiple mRNA isoforms via alternative splicing and alternative promoter usage; four major isoforms arise from two alternative 5′ and two alternative 3′ exons, plus minor isoforms lacking exon 4 or 8. Two alternative 5′ exons each lie downstream of a functional promoter, and naturally occurring haplotypes differ in promoter activity, indicating genetic regulation of GABRA2 expression. RT-PCR and DNA sequencing of human brain mRNA; transient transfection promoter activity assays with naturally occurring haplotype constructs Brain research. Molecular brain research High 15950776
2002 The rat Gabra2 gene 5′-flanking region contains three alternative first exons each preceded by a functional promoter (two lacking TATA/CCAAT elements), generating six 5′-UTR isoforms by alternative splicing; differential activation of these alternative promoters occurs during brain development, and diversity at the 5′-end of transcripts affects GABAA receptor expression. cDNA/genomic DNA alignment, identification of transcription initiation sites, promoter functional characterization; developmental expression analysis Journal of neurochemistry Medium 12354299
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 GABRA2 is correlated with expression of the other three chromosome 4p12 GABAA subunit genes (GABRG1, GABRA4, GABRB1) but not other neural genes; this genotype effect was absent in postmortem adult cortex. iPSC-derived neural cell cultures from rs279858-genotyped donors; qPCR and RNA-seq; BrainCloud and BRAINEAC postmortem brain datasets Alcoholism, clinical and experimental research Medium 26250693
2020 FRMD7 directly interacts with the intracellular loop between transmembrane domains 3 and 4 of GABRA2; INS-causing FRMD7 missense mutations (p.Ala194Thr and p.Arg325Gly) exhibit decreased binding to GABRA2, and loss of frm-3 (FRMD7 homolog) in C. elegans impairs GABAA receptor fluorescence recovery after photobleaching, indicating FRMD7 regulates GABAAR transport/localization through GABRA2 interaction. GST pull-down and co-immunoprecipitation; Western blotting; immunofluorescence; FRAP in C. elegans frm-3 null background with rescue assays Investigative ophthalmology & visual science Medium 32446246
2020 Structural analysis of seven pathogenic GABRA2 missense variants associated with early infantile epileptic encephalopathy localizes them to the transmembrane domain near the desensitization gate, activation gate, or inter-subunit interfaces; equivalent positions are mutated in other Cys-loop receptor epilepsy variants, and pathogenic mutations are enriched in the pore-lining helix. Trio whole-genome sequencing; protein structural modeling; evolutionary sequence conservation analysis Molecular genetics & genomic medicine Low 32347641
2015 In mice, deletion of GABRA2 (α2−/− mice) abolishes methylphenidate's ability to facilitate responding for conditioned reinforcers, paralleling human findings where carriers of GABRA2 addiction-risk SNPs are insensitive to methylphenidate-facilitated conditioned reinforcement and mood effects, suggesting α2-containing GABAA receptor circuits protect against addiction vulnerability. α2 knockout mice; operant conditioned reinforcement task with methylphenidate; parallel human SNP genotype × methylphenidate randomized crossover study Frontiers in behavioral neuroscience Medium 26635556
2015 Exercise increases Gabra2 mRNA expression in the limbic system of aged mice while decreasing it in young mice; the repressive histone mark H3K9me3 at the GABRA2 promoter region decreases with age, and SUV39H1 inhibition (ETP69) reduces H3K9me3 at GABRA2 and BDNF promoters, indicating that H3K9me3-mediated epigenetic regulation modulates GABRA2 expression in an age-dependent manner. Exercise intervention in mice; ChIP for H3K9me3 at GABRA2 promoter; qRT-PCR; pharmacological inhibition of SUV39H1 with ETP69 Frontiers in aging neuroscience Medium 34970138
2018 Binge ethanol consumption reduces Gabra2 mRNA in the central nucleus of the amygdala and bed nucleus of the stria terminalis in female wild-type mice; this reduction is reversed in β-endorphin-deficient female mice (where EtOH instead increases Gabra2 to wild-type naïve levels), demonstrating that β-endorphin modulates sexually dimorphic Gabra2 expression in limbic structures during binge drinking. Drinking-in-the-dark binge model in β-endorphin knockout and wild-type mice; qRT-PCR of Gabra2 mRNA in dissected limbic regions Frontiers in genetics Medium 30555510
2024 A novel de novo GABRA2 missense variant (p.Ala308Val) in the extracellular domain reduces protein expression, impairs co-immunoprecipitation interaction with GABRB3 and GABRG2 subunits (potentially destabilizing the pentameric receptor complex), but does not alter subcellular localization of the mutant protein. Trio whole-exome sequencing; structural modeling; Western blotting; co-immunoprecipitation; immunofluorescence in HEK293T cells Annals of clinical and translational neurology Medium 39737842
2015 In a zebrafish gabra2 morphant model, knockdown of gabra2 disrupts the pattern of cell proliferation during embryonic CNS development, increases apoptosis in mid- and hindbrain, reduces expression of notch1, pax2, fgf8, wnt1, and gad1b, and downregulates neuroD transcriptional activity, indicating that gabra2 plays a role in CNS development including neuronal differentiation and GABAergic circuit formation. Morpholino knockdown in zebrafish; BrdU proliferation assay; TUNEL apoptosis assay; in situ hybridization and gene expression analysis Biochemistry and biophysics reports Medium 29124181

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 124 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 47 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 34 21919924
2013 A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration. Alcohol and alcoholism (Oxford, Oxfordshire) 32 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
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 27 29422393
2013 Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2. Behavior genetics 27 23974430
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 25 29124181
2021 Gabra2 is a genetic modifier of Dravet syndrome in mice. Mammalian genome : official journal of the International Mammalian Genome Society 22 34086081
2012 Gamma-aminobutyric acid A receptor, α-2 (GABRA2) variants as individual markers for alcoholism: a meta-analysis. Psychiatric genetics 22 22555154
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
2021 Exercise Reduces H3K9me3 and Regulates Brain Derived Neurotrophic Factor and GABRA2 in an Age Dependent Manner. Frontiers in aging neuroscience 10 34970138
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 10 29131352
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
2016 Beyond risk: Prospective effects of GABA Receptor Subunit Alpha-2 (GABRA2) × Positive Peer Involvement on adolescent behavior. Development and psychopathology 9 27581089
2021 A quantitative trait variant in Gabra2 underlies increased methamphetamine stimulant sensitivity. Genes, brain, and behavior 8 34677900
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
2015 Mechanisms in the relation between GABRA2 and adolescent externalizing problems. European child & adolescent psychiatry 7 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 3 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

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