Protein / target

Gamma-aminobutyric acid receptor subunit gamma-3

GABRG3Q99928Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
57
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

GABA-gated chloride ion channel activity

Primary system

Nervous system

Strongest disease association

major depressive disorder

Clinical evidence · score 0.61

Therapeutic maturity

Clinically validated target

57 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

57 approved · 9 in clinical development

30 linked trials

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

Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (By similarity). 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) (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride across the cell membrane down their electrochemical gradient (By similarity)

Subcellular location

Postsynaptic cell membraneCell membrane
Domains and Gene Ontology detail (15)

Gene Ontology

  • Cchloride channel complex
  • Cdendrite membrane
  • CGABA-A receptor complex
  • CGABA-ergic synapse
  • Cplasma membrane
  • Cpostsynapse
  • Cpostsynaptic membrane
  • FGABA-A receptor activity
  • FGABA-gated chloride ion channel activity
  • Ftransmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
  • Pchloride transmembrane transport
  • Pgamma-aminobutyric acid signaling pathway

467 aa · 54 kDa · 2 isoforms

Biological roles

Reactome v97

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

Synaptic signallingUniProt · GOChloride transportUniProt · GOLigand-gated signallingUniProt · GOInhibitory neurotransmissionGOIon channel gatingGO
View supporting evidence

Synaptic signalling

  • ·Postsynaptic cell membrane
  • ·GABA-ergic synapse
  • ·postsynapse
  • ·postsynaptic membrane

Chloride transport

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

Ligand-gated signalling

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

Inhibitory neurotransmission

  • ·GABA-ergic synapse
  • ·inhibitory synapse assembly
  • ·synaptic transmission, GABAergic

Ion channel gating

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

PLCL1TRAK2HAP1NSFGABARAPGABRA1GABARA…GABARA…GABRQGABBR2GABRG3

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.

Drugs targeting this protein

4

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Midazolam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Appears in clinical studies involving epilepsy, status epilepticus, Irritability, post-traumatic stress disorder

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

Isoflurane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Appears in clinical studies involving kidney injury, Hydrocephalus, delirium, sedation

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

Halothane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Appears in clinical studies involving septic shock, Sepsis

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

sevoflurane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Appears in clinical studies involving endometrial cancer, myocardial infarction, sedation, delirium

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

migraine disorder1.00

Clinical · overall 0.61

insomnia1.00

Clinical · overall 0.61

epilepsy1.00

Clinical · overall 0.61

major depressive disorder0.99

Clinical · overall 0.61

panic disorder0.99

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Agitation0.60

Clinical

anxiety disorder0.60

Clinical

alcohol dependence0.60

Clinical

Anxiety0.59

Clinical

Seizure0.59

Clinical

Show all associations
major depressive disorder0.61
epilepsy0.61
migraine disorder0.61
insomnia0.61
panic disorder0.60
Agitation0.60
anxiety disorder0.60
alcohol dependence0.60
Anxiety0.59
Seizure0.59

Open Targets ranks 385 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 71 total

MIDAZOLAM HYDROCHLORIDEApproval

amnesia · Seizure · status epilepticus

TETRAZEPAMUnknown
CLOMETHIAZOLEPhase 3

Stroke

BREXANOLONEApproval

postpartum depression · depressive disorder · major depressive disorder

ETOMIDATEApproval

hypertensive disorder · ischemic stroke · sedation

CLONAZEPAMApproval

Seizure · panic disorder · epilepsy

PENTOBARBITAL SODIUMUnknown
HALAZEPAMApproval

anxiety disorder · Anxiety

PROPOFOLApproval

status epilepticus · brain injury · breast cancer

CLOBAZAMApproval

Lennox-Gastaut syndrome · Seizure · anxiety disorder

Tractability

SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Safety liabilities

decreased cardiac contractilitydecreased memorydecreased convulsionsdecreased locomotor activityincreased sleepincreased eatingincreased respiratory ratedecreased sleepmuscle relaxationdecreased body temperaturedecreased paindecreased blood pressure

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.

Show remaining trials (24)

COMPLETED · via Midazolam · NCT01173640

TERMINATED · via Midazolam · NCT00030004

WITHDRAWN · via Midazolam · NCT00938990

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

major depressive disorderWell supported
0.75
agreement 0.600.91
Clinical96%Literature4%

Open Targets aggregate 0.61 · 2 independent evidence families

epilepsyModerately supported
0.75
agreement 0.590.90
Clinical99%Literature1%

Open Targets aggregate 0.61 · 2 independent evidence families

migraine disorderModerately supported
0.75
agreement 0.580.91
Clinical100%

Open Targets aggregate 0.61 · 1 independent evidence family

insomniaModerately supported
0.75
agreement 0.580.91
Clinical100%

Open Targets aggregate 0.61 · 1 independent evidence family

panic disorderModerately supported
0.74
agreement 0.590.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 independent evidence families

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

13

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. 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

  2. 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

  3. New publication2024-01-17
    Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.

    The Journal of pharmacology and experimental therapeutics · 2024 · 14 citations · Europe PMC · via Midazolam

  4. New publication2024-01-17
    Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.

    The Journal of pharmacology and experimental therapeutics · 2024 · 12 citations · Europe PMC · via Midazolam

  5. New publication2019-09-26
    First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound.

    Nature communications · 2019 · 366 citations · Europe PMC · via Midazolam

  6. New publication2018-10-04
    Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy.

    Chest · 2019 · 220 citations · Europe PMC · via Midazolam

  7. New publication2018-04-30
    A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy.

    Gastrointestinal endoscopy · 2018 · 209 citations · Europe PMC · via Midazolam

  8. New publication2015-04-01
    A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy.

    Anesthesia and analgesia · 2015 · 151 citations · Europe PMC · via Midazolam

  9. New publication2011-10-01
    A randomized clinical trial comparing oral, aerosolized intranasal, and aerosolized buccal midazolam.

    Annals of emergency medicine · 2011 · 49 citations · Europe PMC · via Midazolam

  10. Regulatory approval2011-09-04

    Approval: Buccolam (EMA)

    ema · regulatory · ema · via Midazolam

  11. New publication2010-09-15
    A comparison of the effects of etomidate and midazolam on hospital length of stay in patients with suspected sepsis: a prospective, randomized study.

    Annals of emergency medicine · 2010 · 47 citations · Europe PMC · via Midazolam

  12. New publication2003-02-01
    Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003 · 1,387 citations · Europe PMC · via Midazolam

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.