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GeneE
25 sources retrieved ยท Most recent: April 2026 ยท Index updated 15 days ago
โ“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GABRA1
gamma-aminobutyric acid type A receptor subunit alpha1
Chromosome 5 ยท 5q34
NCBI Gene: 2554Ensembl: ENSG00000022355.19HGNC: HGNC:4075UniProt: A8K177
161PubMed Papers
24Diseases
76Drugs
74Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedIon ChannelReceptorTransporter
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
โœ“ Experimental GO Evidenceโœ“ Swiss-Prot Reviewed
GABA-A receptor complexgamma-aminobutyric acid signaling pathwayplasma membranesynaptic transmission, GABAergicdevelopmental and epileptic encephalopathy, 19juvenile myoclonic epilepsyepilepsymajor depressive disorder
โœฆAI Summary

GABRA1 encodes the alpha-1 subunit of gamma-aminobutyric acid type A receptors (GABAARs), heteropentameric ligand-gated chloride channels that mediate primary inhibitory neurotransmission in the brain 1. The alpha-1 subunit forms the GABA binding site at interfaces with beta subunits; GABA activation opens the channel, allowing selective chloride influx that hyperpolarizes neurons and reduces action potential generation 1. Alpha-1-containing GABAARs are predominantly synaptic and exhibit synaptogenic activity, contributing to inhibitory synapse assembly 1. GABRA1 mutations cause developmental and epileptic encephalopathies with variable phenotypes; de novo mutations in GABRA1 have been identified in infantile spasms, Lennox-Gastaut syndrome, and epilepsy of infancy with migrating focal seizures 23. Pathogenic variants predominantly localize to transmembrane domains and extracellular regions, with transmembrane mutations generally producing more severe phenotypes than N-terminal variants 45. All GABRA1 variants identified in large epilepsy cohorts (n>8500) were de novo, indicating dominant inheritance 6. Mutations impair receptor expression and reduce GABA-evoked current amplitudes 1. Additionally, petrosal GABRA1 neurons detect prostaglandins and mediate influenza-induced sickness behavior via an airway-to-brain sensory pathway 7.

Sources cited
1
GABRA1 encodes GABA receptor subunit; mutations reduce receptor expression and GABA-evoked potentials; associated with multiple epilepsy syndromes
PMID: 35850019
2
De novo GABRA1 mutations identified in infantile spasms and Lennox-Gastaut syndrome cohorts
PMID: 23934111
3
De novo GABRA1 mutations identified as novel causes of epilepsy of infancy with migrating focal seizures
PMID: 31618474
4
GABRA1 variants associated with variable epileptic phenotypes; transmembrane variants correlate with more severe phenotypes than N-terminal variants
PMID: 35718920
5
All GABRA1 variants in large epilepsy cohort (>8500 patients) were de novo, indicating dominant inheritance pattern
PMID: 29655203
6
Pathogenic GABRA1 variants in extracellular and transmembrane domains cause decreased surface expression or reduced current with variable epilepsy severity
PMID: 37809401
7
Petrosal GABRA1 neurons detect prostaglandins and mediate influenza-induced sickness behavior via airway-to-brain sensory pathway
PMID: 36890237
Disease Associationsโ“˜24
developmental and epileptic encephalopathy, 19Open Targets
0.77Strong
juvenile myoclonic epilepsyOpen Targets
0.74Strong
epilepsyOpen Targets
0.74Strong
major depressive disorderOpen Targets
0.68Moderate
SeizureOpen Targets
0.63Moderate
insomniaOpen Targets
0.61Moderate
migraine disorderOpen Targets
0.61Moderate
panic disorderOpen Targets
0.60Moderate
AgitationOpen Targets
0.60Moderate
anxiety disorderOpen Targets
0.60Moderate
alcohol dependenceOpen Targets
0.60Moderate
AnxietyOpen Targets
0.59Moderate
generalised epilepsyOpen Targets
0.58Moderate
postpartum depressionOpen Targets
0.58Moderate
PainOpen Targets
0.57Moderate
childhood absence epilepsyOpen Targets
0.57Moderate
status epilepticusOpen Targets
0.57Moderate
Lennox-Gastaut syndromeOpen Targets
0.57Moderate
generalized anxiety disorderOpen Targets
0.56Moderate
HeadacheOpen Targets
0.55Moderate
Developmental and epileptic encephalopathy 19UniProt
Epilepsy, childhood absence 4UniProt
Epilepsy, idiopathic generalized 13UniProt
Juvenile myoclonic epilepsy 5UniProt
Pathogenic Variants74
NM_001127644.2(GABRA1):c.884C>T (p.Thr295Ile)Likely pathogenic
not provided|Developmental and epileptic encephalopathy, 19|Idiopathic generalized epilepsy;Epilepsy, childhood absence 4;Epilepsy, idiopathic generalized, susceptibility to, 13
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 295
NM_001127644.2(GABRA1):c.641G>A (p.Arg214His)Pathogenic
not provided|Developmental and epileptic encephalopathy, 19|Epilepsy, idiopathic generalized, susceptibility to, 13;Idiopathic generalized epilepsy;Epilepsy, childhood absence 4|Epilepsy, idiopathic generalized, susceptibility to, 13;Developmental and epileptic encephalopathy, 19
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 214
NM_001127644.2(GABRA1):c.256-2A>GLikely pathogenic
not provided|Idiopathic generalized epilepsy;Epilepsy, idiopathic generalized, susceptibility to, 13;Epilepsy, childhood absence 4
โ˜…โ˜…โ˜†โ˜†2025
NM_001127644.2(GABRA1):c.922G>A (p.Ala308Thr)Likely pathogenic
Intellectual disability|Developmental and epileptic encephalopathy, 19
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 308
NM_001127644.2(GABRA1):c.166C>T (p.Arg56Cys)Likely pathogenic
Inborn genetic diseases|not provided
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 56
NM_001127644.2(GABRA1):c.440G>A (p.Arg147Gln)Pathogenic
Developmental and epileptic encephalopathy, 19|Epilepsy, childhood absence 4;Epilepsy, idiopathic generalized, susceptibility to, 13;Idiopathic generalized epilepsy
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 147
NM_001127644.2(GABRA1):c.640C>T (p.Arg214Cys)Pathogenic
not provided|Intractable seizure|Idiopathic generalized epilepsy;Epilepsy, childhood absence 4;Epilepsy, idiopathic generalized, susceptibility to, 13|Developmental and epileptic encephalopathy, 19;Epilepsy, idiopathic generalized, susceptibility to, 13|Developmental and epileptic encephalopathy, 19
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 214
NM_001127644.2(GABRA1):c.839C>T (p.Pro280Leu)Likely pathogenic
Developmental and epileptic encephalopathy, 19
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 280
NM_001127644.2(GABRA1):c.865A>G (p.Thr289Ala)Pathogenic
Epilepsy, idiopathic generalized, susceptibility to, 13;Epilepsy, childhood absence 4;Idiopathic generalized epilepsy|not provided
โ˜…โ˜…โ˜†โ˜†2023โ†’ Residue 289
NM_001127644.2(GABRA1):c.869_888del (p.Val290fs)Pathogenic
Idiopathic generalized epilepsy;Epilepsy, idiopathic generalized, susceptibility to, 13;Epilepsy, childhood absence 4|Developmental and epileptic encephalopathy, 19
โ˜…โ˜…โ˜†โ˜†2023โ†’ Residue 290
NM_001127644.2(GABRA1):c.859G>T (p.Val287Leu)Pathogenic
not provided|Developmental and epileptic encephalopathy, 19
โ˜…โ˜…โ˜†โ˜†2022โ†’ Residue 287
NM_001127644.2(GABRA1):c.881C>T (p.Thr294Ile)Pathogenic
not provided
โ˜…โ˜…โ˜†โ˜†2019โ†’ Residue 294
NM_001127644.2(GABRA1):c.637T>A (p.Ser213Thr)Likely pathogenic
Epilepsy, childhood absence 4;Epilepsy, idiopathic generalized, susceptibility to, 13;Idiopathic generalized epilepsy
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 213
NM_001127644.2(GABRA1):c.226A>T (p.Ser76Cys)Likely pathogenic
Developmental and epileptic encephalopathy, 19
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 76
NM_001127644.2(GABRA1):c.255+1G>APathogenic
Inborn genetic diseases
โ˜…โ˜†โ˜†โ˜†2025
NM_001127644.2(GABRA1):c.825C>A (p.Asn275Lys)Pathogenic
Idiopathic generalized epilepsy;Epilepsy, idiopathic generalized, susceptibility to, 13;Epilepsy, childhood absence 4
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 275
NM_001127644.2(GABRA1):c.944G>A (p.Trp315Ter)Pathogenic
Epilepsy, childhood absence 4;Epilepsy, idiopathic generalized, susceptibility to, 13;Idiopathic generalized epilepsy
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 315
NM_001127644.2(GABRA1):c.256-1G>ALikely pathogenic
Epilepsy, childhood absence 4;Epilepsy, idiopathic generalized, susceptibility to, 13;Idiopathic generalized epilepsy
โ˜…โ˜†โ˜†โ˜†2025
NM_001127644.2(GABRA1):c.199G>T (p.Glu67Ter)Pathogenic
Inborn genetic diseases
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 67
NM_001127644.2(GABRA1):c.853T>C (p.Phe285Leu)Pathogenic
not provided
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 285
View on ClinVar โ†—
Drug Targets76
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
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
INDIPLONApproved
GABA receptor alpha-1 subunit positive allosteric modulator
fibromyalgia
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
ZALEPLONApproved
GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator
ZOLPIDEMApproved
GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric modulator
insomnia
ZOLPIDEM TARTRATEApproved
GABA A receptor alpha-1/beta-1/gamma-2 positive allosteric 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
GABARAPProtein interaction96%GABARAPL1Protein interaction95%EFHC1Protein interaction92%PLCL1Protein interaction91%NSFProtein interaction91%HAP1Protein interaction90%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
0%
Liver
0%
Ovary
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
GABRA1GABARAPGABARAPL1EFHC1PLCL1NSFHAP1
PROTEIN STRUCTURE
Preparing viewerโ€ฆ
PDB9EQG ยท 2.40 ร… ยท EM
View on RCSB โ†—
Constraintโ“˜
LOEUFโ“˜
0.28Highly Constrained
pLIโ“˜
1.00Intolerant
Observed/Expected LoF0.13 [0.07โ€“0.28]
RankingsWhere GABRA1 stands among ~20K protein-coding genes
  • #2,792of 20,598
    Most Researched161 ยท top quartile
  • #9of 1,025
    FDA-Approved Drug Targets62 ยท top 1%
  • #992of 5,498
    Most Pathogenic Variants74 ยท top quartile
  • #1,003of 17,882
    Most Constrained (LOEUF)0.28 ยท top 10%
Genes detectedGABRA1
Sources retrieved25 papers
Response timeโ€”
๐Ÿ“„ Sources
25โ–ผ
1
De novo mutations in epileptic encephalopathies.
PMID: 23934111
Nature ยท 2013
1.00
2
Molecular and clinical descriptions of patients with GABA
PMID: 35718920
Epilepsia ยท 2022
0.90
3
Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.
PMID: 29655203
Epilepsia ยท 2018
0.80
4
Genetic variations in GABA metabolism and epilepsy.
PMID: 35850019
Seizure ยท 2022
0.70
5
Understanding paralogous epilepsy-associated GABA
PMID: 39642202
Proc Natl Acad Sci U S A ยท 2024
0.68