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| Symbol | GABBR1 |
| Full Name | Gamma-Aminobutyric Acid Type B Receptor Subunit 1 |
| Chromosome | 6p21.31 |
| NCBI Gene | 2550 |
| Ensembl | ENSG00000204681 |
| OMIM | 603540 |
| UniProt | Q9UBS5 |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Epilepsy |
| Expression | Cerebral [cortex](/brain-regions/cortex), [Hippocampus](/brain-regions/hippocampus), Cerebellum, Thalamus, Basal ganglia |
|
S867G (associated with temporal lobe epilepsy)
A204T (reduced receptor function)
Various splice variants affecting ligand binding |
GABBR1 (Gamma-Aminobutyric Acid Type B Receptor Subunit 1) encodes the GABA-B1 subunit of the metabotropic GABA receptor. GABA-B receptors are the principal inhibitory G-protein coupled receptors in the central nervous system, mediating slow synaptic inhibition through activation of inwardly rectifying potassium channels and inhibition of voltage-gated calcium channels. The GABBR1 subunit contains the orthosteric ligand-binding domain that recognizes GABA and the drug baclofen.
GABBR1 is obligately heterodimerized with GABBR2 to form functional GABA-B receptors. The GABBR1 subunit contributes the ligand-binding venus flytrap domain while GABBR2 provides the G-protein coupling interface. Dysfunction of GABAergic inhibitory signaling through GABA-B receptors has been implicated in multiple neurodegenerative conditions, including Alzheimer's disease and Parkinson's disease.
The protein encoded by GABBR1 is GABA-B Receptor Subunit 1. See the protein page for detailed structural and functional information.
GABBR1 encodes a 960-amino acid transmembrane protein that serves as the ligand-binding subunit of the heterodimeric GABA-B receptor complex. Key functions include:
- Ligand recognition: The N-terminal venus flytrap domain (VFT) binds GABA and pharmacological agonists (baclofen) with high affinity
- Receptor assembly: The coiled-coil domain at the C-terminus mediates obligate heterodimerization with GABBR2
- Synaptic localization: Contains an ER retention signal (RSRR) that is masked upon GABBR2 binding, enabling surface trafficking
- Alternative splicing: Produces two major isoforms — GABBR1a (with two sushi domains for axonal targeting) and GABBR1b (predominantly somatodendritic)
GABA-B receptors couple to Gi/o proteins to mediate:
- Presynaptic inhibition: Inhibition of P/Q-type and N-type calcium channels, reducing neurotransmitter release
- Postsynaptic inhibition: Activation of Kir3/GIRK potassium channels, generating slow inhibitory postsynaptic potentials (sIPSPs)
- Adenylyl cyclase inhibition: Reduction of cAMP levels, affecting CREB-dependent gene transcription
- MAPK modulation: Regulation of ERK1/2 signaling pathways relevant to neuronal survival
GABAergic dysfunction is increasingly recognized in Alzheimer's disease:
- GABBR1 expression is reduced in the hippocampus and temporal cortex of AD patients
- Loss of GABA-B receptor-mediated inhibition contributes to neuronal hyperexcitability, a feature observed in early AD
- Amyloid-beta oligomers disrupt GABA-B receptor trafficking and surface expression
- GABA-B receptor activation has shown neuroprotective effects against amyloid-beta toxicity in experimental models
- APOE4 carriers show accelerated decline in GABAergic interneuron function
In Parkinson's disease, GABA-B receptors play roles in basal ganglia circuitry:
- Altered GABBR1 expression in the striatum and globus pallidus of PD patients
- GABA-B receptors on striatopallidal neurons modulate indirect pathway activity
- Baclofen (GABA-B agonist) affects motor function through basal ganglia circuits
- Alpha-synuclein pathology affects GABAergic interneurons in the substantia nigra
- GABBR1 variants (S867G, A204T) are associated with temporal lobe epilepsy and generalized epilepsy syndromes
- GABBR1 knockout mice exhibit spontaneous epileptiform activity and seizures
- Absence epilepsy models show altered GABA-B receptor function in thalamocortical circuits
GABBR1 is broadly expressed throughout the central nervous system with highest levels in:
- Hippocampus: CA1 and CA3 pyramidal neurons, dentate gyrus granule cells
- Cerebral cortex: Layers II/III and V, particularly in GABAergic interneurons
- Cerebellum: Purkinje cells and granule cells
- Thalamus: Relay neurons and reticular nucleus
- Basal ganglia: Medium spiny neurons of the striatum, globus pallidus
- Substantia nigra: Pars reticulata GABAergic neurons
Expression data from the Allen Brain Atlas confirms widespread distribution with regional variation in isoform ratios (GABBR1a vs GABBR1b).