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Protein / target

Gamma-aminobutyric acid receptor subunit alpha-1

Encoded byGABRA1P14867Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
62
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

GABA-gated chloride ion channel

Strongest disease association

Developmental and epileptic encephalopathy, 19

Via encoding gene GABRA1 · Genetic evidence · score 0.91

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

View complete UniProt function annotation

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, PubMed:30602789). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity)

Subcellular location

Postsynaptic cell membraneCell membraneCytoplasmic vesicle membrane
Domains and Gene Ontology detail (18)

Gene Ontology

  • Cchloride channel complex
  • Ccytoplasmic vesicle membrane
  • Cdendrite membrane
  • Cdendritic spine
  • CGABA receptor complex
  • CGABA-A receptor complex
  • CGABA-ergic synapse
  • Cplasma membrane
  • Cpostsynapse
  • Cpostsynaptic specialization membrane
  • FGABA-A receptor activity
  • FGABA-gated chloride ion channel activity

456 aa · 52 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Inhibitory neurotransmissionUniProt · GOChloride transportUniProt · GOLigand-gated signallingUniProt · GOIon channel gatingGOReceptor tyrosine kinase signallingReactome
View supporting evidence

Inhibitory neurotransmission

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-amino…
  • ·GABA-ergic synapse
  • ·inhibitory synapse assembly
  • ·synaptic transmission, GABAergic

Chloride transport

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-amino…
  • ·chloride channel complex
  • ·GABA-gated chloride ion channel activity

Ligand-gated signalling

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-amino…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

  • ·GABA-gated chloride ion channel activity
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Receptor tyrosine kinase signalling

  • ·Signaling by ERBB4
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GABRG2GABRB2GABRB3GABRB1TRAK2HAP1NSFPLCL1GABBR2CLCN2GABRA1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

9 medicines · 6 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Anxiety Disorders3 medicines
Status Epilepticus2 medicines
Epileptic Syndromes1 medicine
Migraine Disorders1 medicine

62 medicines meet Open Targets' target-level approved-medicine definition; the 9 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

13

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Midazolam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Status Epilepticus

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

Isoflurane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

Halothane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

sevoflurane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

propofol
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

clobazam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

View all 13 targeting drugs
clonazepam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

lorazepam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Anxiety Disorders, Status Epilepticus

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

meprobamate
ApprovedAgonist

GABA-A receptor; anion channel agonist

Indicated for Anxiety Disorders

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

topiramate
ApprovedPositive modulator

GABA-A receptor; anion channel positive modulator

Indicated for Epilepsy, Migraine Disorders, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 37 recorded protein targets — broad pharmacology

cenobamate
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 26 recorded protein targets — broad pharmacology

ganaxolone
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Epileptic Syndromes, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

alprazolam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Anxiety Disorders

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GABRA1

Gene-level evidence surfaced through the gene GABRA1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Juvenile myoclonic epilepsy
0.94Well supported

Genetic evidence dominant · Open Targets 0.74

Developmental and epileptic encephalopathy, 19
0.93Well supported

Genetic evidence dominant · Open Targets 0.76

Epilepsy
0.90Well supported

Clinical evidence dominant · Open Targets 0.74

Major depressive disorder
0.85Well supported

Clinical evidence dominant · Open Targets 0.67

Sleep Initiation and Maintenance Disorders
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

View evidence synthesis (5)
Juvenile myoclonic epilepsyWell supported
0.94
agreement 0.821.00
Genetic73%Animal model24%Literature3%Genetic literaturedup

Open Targets aggregate 0.74 · 3 independent evidence families · 1 not counted as duplicate

Developmental and epileptic encephalopathy, 19Well supported
0.93
agreement 0.811.00
Genetic83%Animal model16%Literature1%Genetic literaturedup

Open Targets aggregate 0.76 · 3 independent evidence families · 1 not counted as duplicate

EpilepsyWell supported
0.90
agreement 0.791.00
Clinical54%Genetic40%Literature6%Genetic literaturedup

Open Targets aggregate 0.74 · 3 independent evidence families · 1 not counted as duplicate

Major depressive disorderWell supported
0.85
agreement 0.750.96
Clinical63%Genetic34%Literature3%

Open Targets aggregate 0.67 · 3 independent evidence families

Sleep Initiation and Maintenance DisordersWell supported
0.75
agreement 0.600.91
Clinical98%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Developmental and epileptic encephalopathy, 190.76
Juvenile myoclonic epilepsy0.74
Epilepsy0.74
Major depressive disorder0.67
Sleep Initiation and Maintenance Disorders0.61
Migraine Disorders0.61
Panic disorder0.60

Drug development

76 compounds recorded · 62 approved · 9 in clinical development · 5 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 13 drugs that target this protein in Forefront's canonical graph (9 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
HALAZEPAMApproval
QUAZEPAMApproval
THIOPENTALApproval
CLONAZEPAMApproval
PROPOFOLApproval
MEPROBAMATEApproval
METHAQUALONE HYDROCHLORIDEUnknown
PENTOBARBITAL SODIUMUnknown
METHOXYFLURANEApproval
FLUNITRAZEPAMApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

increased eatingLynch et al. (2017)seizure (when used as a BZD antidote)Bowes et al. (2012)decreased body temperatureLynch et al. (2017)muscle relaxationBowes et al. (2012)decreased painLynch et al. (2017)decreased blood pressureLynch et al. (2017)dizzinessBowes et al. (2012)drug abuse/dependenceLynch et al. (2017)Occurrence, Epileptic seizureAOP-WikiconvulsionsLynch et al. (2017)anterograde amnesiaBowes et al. (2012)ataxiaLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

UNKNOWN · via topiramate · NCT06089356

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 7 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-08-13

    NMDAR Modulation As a Therapeutic Target and Probe of Neural Dysfunction in OCD

    Status changed to Completed · ClinicalTrials.gov · via Midazolam

  2. Regulatory approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  3. Trial status changed2026-07-22

    A Phase 1, 3-part, Open-label Study to Evaluate the Effects of KarXT Administration on the Pharmacokinetics of Midazolam, Fexofenadine, and Digoxin in Healthy Adult Participants

    Status changed to Completed · ClinicalTrials.gov · via Midazolam

  4. Trial status changed2026-07-20

    A Phase 1 Study to Evaluate the Effect of Multiple Doses of ABBV-722 on the Pharmacokinetics of Cocktail Probe Substrates of CYP3A and Select Transporters in Healthy Adult Subjects

    Status changed to Active, not recruiting · ClinicalTrials.gov · via Midazolam

  5. Regulatory approval2026-07-14

    Approval: PROPOFOL (ANDA220857)

    fda · regulatory · fda · via propofol

  6. Regulatory approval2026-07-13

    Approval: ALPRAZOLAM (ANDA213204)

    fda · regulatory · fda · via alprazolam

  7. Trial status changed2026-07-13

    Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder

    Status changed to Completed · ClinicalTrials.gov · via lorazepam

  8. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  9. Supplemental approval2026-06-29

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  10. New publication2025-02-08
    Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.

    Journal of advanced research · 2025 · 9 citations · Europe PMC · via sevoflurane

  11. Product recall2024-11-18

    Recall (Class I): CLONAZEPAM

    fda · safety · fda · via clonazepam

  12. Safety communication2024-06-20

    Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

    mhra · safety · mhra · via topiramate

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.