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ยฉ 2026 GeneE
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GeneE
10 sources retrieved ยท Most recent: April 2026 ยท Index updated 15 days ago
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GABRA3
gamma-aminobutyric acid type A receptor subunit alpha3
Chromosome X ยท Xq28
NCBI Gene: 2556Ensembl: ENSG00000011677.14HGNC: HGNC:4077UniProt: P34903
62PubMed Papers
21Diseases
74Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
โœ“ Experimental GO Evidenceโœ“ Swiss-Prot Reviewed
protein bindingGABA-A receptor activityGABA-gated chloride ion channel activityplasma membranemigraine disorderepilepsymajor depressive disorderinsomnia
โœฆAI Summary

GABRA3 encodes the alpha3 subunit of the GABA type A receptor, a heteropentameric ligand-gated chloride channel fundamental to GABAergic inhibitory neurotransmission in the brain 12. The alpha3 subunit assembles with four other subunits around a central pore, with GABA binding sites located at alpha-beta subunit interfaces. GABA activation allows chloride anion influx across the postsynaptic membrane, hyperpolarizing neurons and reducing action potential generation, thereby suppressing nerve transmission 12. GABRA3 is located on chromosome X and is primarily expressed in adult brain tissue 3. Pathogenic GABRA3 variants cause X-linked epilepsy with variable phenotypes depending on functional consequence 4. Gain-of-function variants produce severe, treatment-resistant epilepsy with profound intellectual disability disproportionately affecting males, while loss-of-function variants yield milder behavioral and language phenotypes with minimal seizures 4. Beyond neurology, GABRA3 expression is aberrantly activated in breast cancer where it promotes AKT-mediated metastasis, though A-to-I mRNA editing suppresses this pro-invasive activity 5. GABRA3 also regulates social feeding behavior in C. elegans through conserved autism-associated pathways 6. Recent evidence suggests GABRA3 involvement in cardiovascular disease pathogenesis through phthalate-induced toxicity mechanisms 7.

Sources cited
1
GABRA3 forms part of the GABA-gated chloride channel and mediates chloride influx for neuronal inhibition
PMID: 16412217
2
GABRA3 is an alpha subunit of heteropentameric GABAR channels mediating inhibitory synaptic transmission
PMID: 29053855
3
GABRA3 is located on mouse X chromosome homologous to human Xq28
PMID: 1684949
4
Gain-of-function GABRA3 variants cause severe treatment-resistant epilepsy and intellectual disability in males; loss-of-function variants produce milder phenotypes
PMID: 41289009
5
GABRA3 activates AKT pathway to promote breast cancer metastasis; A-to-I editing suppresses invasion
PMID: 26869349
6
GABRA3 (avr-15 ortholog) regulates social feeding behavior in C. elegans through conserved autism-associated pathways
PMID: 39468047
7
GABRA3 is identified as a core target in phthalate-induced cardiovascular toxicity mechanisms
PMID: 40653100
Disease Associationsโ“˜21
migraine disorderOpen Targets
0.61Moderate
epilepsyOpen Targets
0.61Moderate
major depressive disorderOpen Targets
0.61Moderate
insomniaOpen Targets
0.61Moderate
panic disorderOpen Targets
0.60Moderate
AgitationOpen Targets
0.60Moderate
anxiety disorderOpen Targets
0.60Moderate
alcohol dependenceOpen Targets
0.59Moderate
SeizureOpen Targets
0.59Moderate
AnxietyOpen Targets
0.59Moderate
postpartum depressionOpen Targets
0.58Moderate
PainOpen Targets
0.57Moderate
status epilepticusOpen Targets
0.57Moderate
generalized anxiety disorderOpen Targets
0.56Moderate
HeadacheOpen Targets
0.55Moderate
Lennox-Gastaut syndromeOpen Targets
0.55Moderate
depressive disorderOpen Targets
0.53Moderate
Stiff-Person syndromeOpen Targets
0.53Moderate
partial epilepsyOpen Targets
0.51Moderate
sedationOpen Targets
0.51Moderate
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic featuresUniProt
Pathogenic Variants5
NM_000808.4(GABRA3):c.830A>G (p.Tyr277Cys)Likely pathogenic
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features
โ˜…โ˜†โ˜†โ˜†2023โ†’ Residue 277
NM_000808.4(GABRA3):c.1421A>G (p.Tyr474Cys)Pathogenic
Inborn genetic diseases|Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features
โ˜…โ˜†โ˜†โ˜†2018โ†’ Residue 474
NM_000808.4(GABRA3):c.497C>T (p.Thr166Met)Pathogenic
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features
โ˜†โ˜†โ˜†โ˜†2022โ†’ Residue 166
NC_000023.11:g.152277607_152451201dupPathogenic
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features
โ˜†โ˜†โ˜†โ˜†2022
NM_000808.4(GABRA3):c.725A>T (p.Gln242Leu)Pathogenic
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features
โ˜†โ˜†โ˜†โ˜†2022โ†’ Residue 242
View on ClinVar โ†—
Drug Targets74
ABP-700Phase II
GABA-A receptor; anion channel agonist
ACAMPROSATEApproved
Glutamate [NMDA] receptor antagonist
alcohol dependence
ACAMPROSATE CALCIUMApproved
Glutamate [NMDA] receptor antagonist
alcohol dependence
ADIPIPLONPhase II
GABA-A receptor; anion channel partial agonist
sleep-wake disorder
ALPRAZOLAMApproved
GABA-A receptor; anion channel positive allosteric modulator
panic disorder
AZD6280Phase I
GABA receptor alpha-2 subunit positive allosteric modulator
anxiety disorder
AZD7325Phase II
GABA receptor alpha-2 subunit positive allosteric modulator
anxiety disorder
BREXANOLONEApproved
GABA-A receptor; anion channel positive allosteric modulator
BUTABARBITALApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
BUTALBITALApproved
GABA-A receptor; anion channel positive allosteric modulator
migraine disorder
CENOBAMATEApproved
Sodium channel alpha subunit inhibitor
Seizure
CHLORDIAZEPOXIDEApproved
GABA-A receptor; anion channel positive allosteric modulator
anxiety disorder
CHLORDIAZEPOXIDE HYDROCHLORIDEApproved
GABA-A receptor; anion channel positive allosteric modulator
CIPEPOFOLPhase III
GABA-A receptor; anion channel agonist
CLOBAZAMApproved
GABA-A receptor; anion channel positive allosteric modulator
CLOMETHIAZOLEPhase III
GABA-A receptor; anion channel positive allosteric modulator
stroke
CLONAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
CLORAZEPATE DIPOTASSIUMApproved
GABA-A receptor; anion channel positive allosteric modulator
CLORAZEPIC ACIDApproved
GABA-A receptor; anion channel positive allosteric modulator
anxiety disorder
CLOTIAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
anxiety disorder
DARIGABATPhase II
GABA-A receptor; anion channel agonist
Chronic pain
DESFLURANEApproved
Potassium channel subfamily K member 10 opener
DIAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
Agitation
ENFLURANEApproved
Potassium channel subfamily K member 10 opener
ESTAZOLAMApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
ESZOPICLONEApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
ETHCHLORVYNOLApproved
GABA-A receptor; anion channel positive modulator
insomnia
ETIFOXINEApproved
GABA-A receptor; anion channel antagonist
Anxiety
ETOMIDATEApproved
GABA-A receptor; anion channel positive modulator
FLUMAZENILApproved
GABA-A receptor; anion channel allosteric antagonist
FLUNITRAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
FLURAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
FLURAZEPAM HYDROCHLORIDEApproved
GABA-A receptor; anion channel positive allosteric modulator
GANAXOLONEApproved
GABA-A receptor; anion channel positive allosteric modulator
epilepsy
GLUTETHIMIDEApproved
GABA-A receptor; anion channel positive modulator
insomnia
HALAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
anxiety disorder
HALOTHANEApproved
Potassium channel subfamily K member 10 opener
ISOFLURANEApproved
Potassium channel subfamily K member 2 opener
LORAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
major depressive disorder
MEPROBAMATEApproved
GABA-A receptor; anion channel agonist
anxiety disorder
METHAQUALONEUNKNOWN
GABA-A receptor; anion channel positive allosteric modulator
insomnia
METHAQUALONE HYDROCHLORIDEUNKNOWN
GABA-A receptor; anion channel positive allosteric modulator
METHARBITALApproved
GABA-A receptor; anion channel positive allosteric modulator
epilepsy
METHOHEXITALApproved
GABA-A receptor; anion channel positive allosteric modulator
METHOXYFLURANEApproved
GABA-A receptor; anion channel positive modulator
METHYPRYLONApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
MIDAZOLAMApproved
GABA-A receptor; anion channel positive allosteric modulator
epilepsy
MIDAZOLAM HYDROCHLORIDEApproved
GABA-A receptor; anion channel positive allosteric modulator
amnesia
OXAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
Agitation
PADSEVONILPhase II/III
GABA-A receptor; anion channel partial agonist
epilepsy
PAGOCLONEPhase II/III
GABA-A receptor; anion channel positive allosteric modulator
anxiety disorder
PENTOBARBITALApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
PENTOBARBITAL SODIUMUNKNOWN
GABA-A receptor; anion channel positive allosteric modulator
PRAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
anxiety disorder
PRIMIDONEApproved
GABA-A receptor; anion channel positive allosteric modulator
epilepsy
PROPOFOLApproved
GABA-A receptor; anion channel positive allosteric modulator
QUAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
REMIMAZOLAMApproved
GABA-A receptor; anion channel positive allosteric modulator
REMIMAZOLAM BESYLATEApproved
GABA-A receptor; anion channel positive allosteric modulator
RESEQUINILPhase II
GABA-A receptor; anion channel inverse agonist
epilepsy
SECOBARBITALApproved
GABA-A receptor; anion channel positive allosteric modulator
SECOBARBITAL SODIUMUNKNOWN
GABA-A receptor; anion channel positive allosteric modulator
SEVOFLURANEApproved
Glycine receptor (alpha-1/beta) positive modulator
TALBUTALApproved
GABA-A receptor; anion channel positive allosteric modulator
Irritability
TEMAZEPAMApproved
GABA-A receptor; anion channel positive allosteric modulator
insomnia
TETRAZEPAMUNKNOWN
GABA-A receptor; anion channel positive allosteric modulator
THIAMYLALApproved
GABA-A receptor; anion channel positive allosteric modulator
THIOPENTALApproved
GABA-A receptor; anion channel positive allosteric modulator
THIOPENTAL SODIUMPhase I
GABA-A receptor; anion channel positive allosteric modulator
amnesia
TOPIRAMATEApproved
Glutamate receptor ionotropic AMPA antagonist
epilepsy
TRIAZOLAMApproved
GABA-A receptor; anion channel positive allosteric modulator
TRICLOFOS SODIUMApproved
GABA-A receptor; anion channel positive modulator
insomnia
ZOPICLONEApproved
GABA-A receptor; agonist GABA site positive allosteric modulator
insomnia
ZURANOLONEApproved
GABA-A receptor; anion channel positive allosteric modulator
postpartum depression
Related Genes
TRAK2Protein interaction97%GABARAPProtein interaction96%GABARAPL1Protein interaction95%HAP1Protein interaction94%GABRB3Protein interaction93%PLCL1Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
1%
Heart
0%
Ovary
0%
Lung
0%
Liver
0%
Gene Interaction Network
Click a node to explore
GABRA3TRAK2GABARAPGABARAPL1HAP1GABRB3PLCL1
PROTEIN STRUCTURE
Preparing viewerโ€ฆ
PDB9CTP ยท 3.62 ร… ยท EM
View on RCSB โ†—
Constraintโ“˜
LOEUFโ“˜
0.56Moderately Constrained
pLIโ“˜
0.89Intermediate
Observed/Expected LoF0.33 [0.20โ€“0.56]
RankingsWhere GABRA3 stands among ~20K protein-coding genes
  • #7,459of 20,598
    Most Researched62
  • #28of 1,025
    FDA-Approved Drug Targets58 ยท top 5%
  • #3,563of 5,498
    Most Pathogenic Variants5
  • #3,669of 17,882
    Most Constrained (LOEUF)0.56 ยท top quartile
Genes detectedGABRA3
Sources retrieved10 papers
Response timeโ€”
๐Ÿ“„ Sources
10โ–ผ
1
Activation of nuclear receptor pregnane-X-receptor protects against abdominal aortic aneurysm by inhibiting oxidative stress.
PMID: 39427444
Redox Biol ยท 2024
1.00
2
Epigenetic Coactivation of MAGEA6 and CT-GABRA3 Defines Orientation of a Segmental Duplication in the Human X Chromosome.
PMID: 31593956
Cytogenet Genome Res ยท 2019
0.90
3
Association of genetic variants in GABRA3 gene and thyrotoxic hypokalaemic periodic paralysis in Thai population.
PMID: 17970773
Clin Endocrinol (Oxf) ยท 2008
0.80
4
The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis.
PMID: 26869349
Nat Commun ยท 2016
0.70
5
Conserved autism-associated genes tune social feeding behavior in C. elegans.
PMID: 39468047
Nat Commun ยท 2024
0.60