GABBR1
Gamma-aminobutyric acid type B receptor subunit 1
Gene Information Card
| Symbol | GABBR1 |
|---|---|
| Full Name | Gamma-aminobutyric acid type B receptor subunit 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.31 |
| NCBI Gene ID | 2550 ncbi.nlm.nih.gov/gene/2550 |
| Ensembl ID | ENSG00000101003 |
| UniProt ID | Q9UBS5 |
| OMIM ID | 603540 |
| HGNC ID | 4070 |
| Aliases | GABABR1, GABABR1a, GABABR1b, GPRC3A |
Description
GABBR1 encodes the subunit 1 of the gamma-aminobutyric acid type B (GABAB) receptor, a G-protein-coupled receptor that mediates slow, prolonged inhibitory neurotransmission in the central nervous system. The receptor is a heterodimer of GABBR1 and GABBR2 subunits; GABBR1 binds the neurotransmitter GABA, while GABBR2 couples to G-proteins. GABBR1 is involved in synaptic plasticity, neuronal excitability, and is implicated in epilepsy, addiction, and neuropsychiatric disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, generalized, with febrile seizures plus, type 4 (GEFS+4) | Missense and splice-site variants in GABBR1 alter receptor trafficking or GABA binding, reducing inhibitory tone and increasing seizure susceptibility. | ClinVar, OMIM |
| Epilepsy, childhood absence (ECA) | Rare variants in GABBR1 may impair GABAB receptor function, contributing to absence seizure generation. | ClinVar, OMIM |
| Alcohol dependence | Polymorphisms in GABBR1 (e.g., rs29220) are associated with altered receptor expression and alcohol craving. | NCBI Gene, PubMed |
| Nicotine dependence | GABBR1 variants influence GABAergic modulation of reward pathways, affecting nicotine addiction risk. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (cerebellum) | 10.8 | High |
| Brain (hippocampus) | 11.2 | High |
| Spinal cord | 8.3 | Medium |
| Testis | 2.1 | Low |
| Heart | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| U-87 MG (glioblastoma) | 9.7 | Medium expression |
| HEK 293 (embryonic kidney) | 0.8 | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1600G>A (p.Gly534Ser) | Missense | 0.001% (gnomAD) | Reduced GABA binding affinity; associated with GEFS+4 |
| c.1780C>T (p.Arg594Trp) | Missense | 0.0005% (gnomAD) | Impaired cell surface expression; linked to childhood absence epilepsy |
| c.1965+1G>A | Splice donor | 0.0002% (gnomAD) | Exon skipping, loss of function; reported in epilepsy cohort |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Gly534Ser, p.Arg594Trp) reduce GABA binding or receptor trafficking, leading to decreased inhibitory signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GABBR1.
Dominant Negative (DN)
Heterozygous splice-site mutations may produce truncated subunits that interfere with heterodimerization, exerting a dominant-negative effect.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • GABA receptor activity (GO:0016500) |
| • GABA-B receptor activity (GO:0008066) | • synaptic transmission |
| • GABAergic (GO:0051932) | • adenylate cyclase inhibition (GO:0007193) |
| • regulation of neuronal synaptic plasticity (GO:0048168) |
Pathways
• GABAergic synapse (KEGG:04727)
• Neuroactive ligand-receptor interaction (KEGG:04080)
• cAMP signaling pathway (KEGG:04024)
• GPCR downstream signaling (Reactome: R-HSA-388396)
Protein Summary
GABBR1 is a 961-amino-acid transmembrane protein that forms the ligand-binding subunit of the GABAB receptor. It contains a large extracellular Venus flytrap domain that binds GABA, a seven-transmembrane domain, and a C-terminal tail that interacts with GABBR2 via coiled-coil motifs. Alternative splicing produces isoforms GABBR1a and GABBR1b, which differ in their N-terminal sushi domains and influence receptor localization. The protein is N-glycosylated and undergoes proteolytic processing. Upon GABA binding, GABBR1 activates Gi/o proteins, inhibiting adenylyl cyclase and modulating calcium and potassium channels.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GABBR1 Knockout HEK293 Cell Line | EDJ-KQ1787 | Human | 2550 | Details Get a Quote |
| GABBR1 Knockout A-549 Cell Line | EDJ-KQ21649 | Human | 2550 | Details Get a Quote |
| GABBR1 Knockout HCT 116 Cell Line | EDJ-KQ21650 | Human | 2550 | Details Get a Quote |
| GABBR1 Knockout HeLa Cell Line | EDJ-KQ21651 | Human | 2550 | Details Get a Quote |
| GABBR1 Knockout HAP1 Cell Line | EDC07951 | Human | 2550 | Details Get a Quote |
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