Protein / target
Gamma-aminobutyric acid type B receptor subunit 1
Protein at a glance
Biological role
G protein-coupled GABA receptor
Strongest disease association
Neurodevelopmental disorder with language delay and variable cognitive abnormalities
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and GABBR2.
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Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:36103875, 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:10906333, PubMed:24305054, PubMed:9872744). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9844003). 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:9844003, 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). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:24305054, PubMed:9844003, PubMed:9872316)
Subcellular location
Domains and Gene Ontology detail (37)Hide
Domains & features
Gene Ontology
- Caxolemma
- Cdendritic shaft
- Cdendritic spine
- Cendoplasmic reticulum membrane
- Cextracellular space
- CG protein-coupled receptor heterodimeric complex
- CGABA receptor complex
- CGABA-ergic synapse
- Cglutamatergic synapse
- Cmitochondrial membrane
- Cneuronal cell body
- Cplasma membrane
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Inhibitory neurotransmission
- ·Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and G…
- ·GABA-ergic synapse
- ·synaptic transmission, GABAergic
Cell proliferation & survival
- ·negative regulation of cell population proliferation
Lipid & lipoprotein metabolism
- ·Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and G…
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
- ·G protein-coupled neurotransmitter receptor activity involved in regulation of postsynap…
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.
Approved medicines with mapped indications
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.
2 medicines meet Open Targets' target-level approved-medicine definition; the 1 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
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.
GABA-B receptor agonist
Indicated for Brain Injuries, Brain Injuries, Traumatic, Cerebral Palsy, Multiple Sclerosis
GABA-B receptor agonist
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
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 GABBR1
Gene-level evidence surfaced through the gene GABBR1that 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.
View evidence synthesis (5)Hide
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.
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Drug development
7 compounds recorded · 2 approved · 5 in clinical development
View all recorded compounds (7)Hide
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 molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (11)Hide
Raw Open Targets tractability assessment buckets, by modality.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets 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.
- 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.