Protein / target
Gamma-aminobutyric acid type B receptor subunit 2
Protein at a glance
Biological role
Transmembrane signaling receptor activity
Primary system
Nervous system
Strongest disease association
developmental and epileptic encephalopathy, 59
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
2 approved · 5 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
Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:9872316, PubMed:9872744). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644, PubMed:10773016, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:9872744). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:22660477, PubMed:9872744). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644, PubMed:22660477, PubMed:9872316, PubMed:9872744). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable)
Subcellular location
Domains and Gene Ontology detail (16)Hide
Gene Ontology
- Ccytoplasm
- CG protein-coupled receptor heterodimeric complex
- CGABA receptor complex
- Cneuron projection
- Cplasma membrane
- Cpostsynaptic membrane
- FG protein-coupled GABA receptor activity
- Fprotein heterodimerization activity
- Ftransmembrane signaling receptor activity
- Padenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- Pchemical synaptic transmission
- PG protein-coupled receptor signaling pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Synaptic signalling
- ·Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and G…
- ·Postsynaptic cell membrane
- ·postsynaptic membrane
- ·chemical synaptic transmission
G protein-coupled signalling
- ·Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and G…
- ·G protein-coupled receptor heterodimeric complex
- ·G protein-coupled GABA receptor activity
- ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Inhibitory neurotransmission
- ·Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and G…
- ·synaptic transmission, GABAergic
View underlying pathways (5)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-B receptor agonist
Appears in clinical studies involving Spasticity, cerebral palsy, multiple sclerosis, Rigidity
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.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 270 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 · 7 total
fragile X syndrome · Spasticity · multiple sclerosis
schizophrenia · Alzheimer disease · succinic semialdehyde dehydrogenase deficiency
Spasticity · cerebral palsy · multiple sclerosis
gastroesophageal reflux disease
fragile X syndrome · autism spectrum disorder · Spasticity
idiopathic hypersomnia · Sleep disturbance · narcolepsy
narcolepsy-cataplexy syndrome · narcolepsy · Cataplexy
Tractability
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.
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 a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationFORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study.
- New publicationBiobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study.
- New publicationPrevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.
- New publicationA human laboratory pilot study with baclofen in alcoholic individuals.
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.