Protein / target
Gamma-aminobutyric acid receptor subunit gamma-2
Protein at a glance
Biological role
GABA-gated chloride ion channel activity
Primary system
Nervous system
Strongest disease association
Generalized epilepsy with febrile seizures-plus
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
60 approved · 9 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
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 (PubMed:14993607, PubMed:16412217, PubMed:23909897, PubMed:2538761, PubMed:25489750, PubMed:27864268, 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:14993607, PubMed:16412217, PubMed:2538761, PubMed:27864268, PubMed:29950725, PubMed:30602789). Gamma-2/GABRG2-containing GABAARs are found at both synaptic and extrasynaptic sites (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). Extrasynaptic gamma-2-containing receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response in a gamma-2 subunit-controlled manner (By similarity)
Subcellular location
Domains and Gene Ontology detail (23)Hide
Gene Ontology
- Caxon
- Cchloride channel complex
- Ccytoplasmic vesicle membrane
- Cdendrite membrane
- Cdendritic spine
- CGABA-A receptor complex
- CGABA-ergic synapse
- Cplasma membrane
- Cpostsynapse
- Cpostsynaptic membrane
- Cpostsynaptic specialization membrane
- Fbenzodiazepine receptor activity
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Inhibitory neurotransmission
- ·Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
- ·GABA-ergic synapse
- ·inhibitory synapse assembly
- ·negative regulation of synaptic transmission, GABAergic
Synaptic signalling
- ·Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
- ·Postsynaptic cell membrane
- ·GABA-ergic synapse
- ·postsynapse
Chloride transport
- ·Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
- ·chloride channel complex
- ·chloride channel activity
- ·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…
Ion channel gating
- ·GABA-gated chloride ion channel activity
- ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
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.
GABA-A receptor; anion channel positive allosteric modulator
Appears in clinical studies involving epilepsy, status epilepticus, Irritability, post-traumatic stress disorder
GABA-A receptor; anion channel positive allosteric modulator
Appears in clinical studies involving kidney injury, Hydrocephalus, delirium, sedation
GABA-A receptor; anion channel positive allosteric modulator
Appears in clinical studies involving septic shock, Sepsis
GABA-A receptor; anion channel positive allosteric modulator
Appears in clinical studies involving endometrial cancer, myocardial infarction, sedation, delirium
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 1,386 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 · 74 total
anxiety disorder · Anxiety
kidney injury · Hydrocephalus · delirium
insomnia · Parkinson disease · insomnia
insomnia
alcohol dependence · Tourette syndrome
insomnia
anxiety disorder
insomnia
Tractability
Safety liabilities
Clinical trials
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)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
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.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
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.
- Trial status changed
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
- New publicationNeonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.
- New publicationNeuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.
- New publicationSex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.
- New publicationFirst-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound.
- New publicationSafety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy.
- New publicationA phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy.
- New publicationA Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy.
- New publicationA randomized clinical trial comparing oral, aerosolized intranasal, and aerosolized buccal midazolam.
- Regulatory approval
Approval: Buccolam (EMA)
- New publicationA comparison of the effects of etomidate and midazolam on hospital length of stay in patients with suspected sepsis: a prospective, randomized study.
- New publicationEarly exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.
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.