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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GABBR1
gamma-aminobutyric acid type B receptor subunit 1
Chromosome 6 Β· 6p22.1
NCBI Gene: 2550Ensembl: ENSG00000204681.11HGNC: HGNC:4070UniProt: A0A0G2JKF9
152PubMed Papers
21Diseases
7Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingplasma membraneG protein-coupled GABA receptor activityG protein-coupled receptor heterodimeric complexneurodevelopmental disorder with language delay and variable cognitive abnormalitiesSpasticitymultiple sclerosisRigidity
✦AI Summary

GABBR1 encodes the gamma-aminobutyric acid type B receptor subunit 1, which forms obligatory heterodimers with GABBR2 to mediate prolonged neuronal inhibition in the central nervous system 1. The receptor functions through G protein-coupled signaling pathways, inhibiting adenylyl cyclase and modulating neurotransmitter release 2. GABBR1 plays critical roles beyond traditional neurotransmission, including regulation of hematopoietic stem and progenitor cell proliferation and function, with Gabbr1-knockout mice showing reduced HSPC numbers and diminished reconstitution capacity 3. The receptor also mediates neuro-immune interactions, as enteric GABAergic neuron-derived GABA inhibits IL-17A production in intestinal ILC3 cells through GABBR1/GABBR2-dependent pathways 4. Additionally, GABBR1 regulates specific neuronal subtypes controlling locomotion, with Gabbr1 knockdown in nigrostriatal dopaminergic neurons affecting movement termination 5. Clinically, de novo GABBR1 variants cause neurodevelopmental disorders with motor/language delays and epilepsy, with functional studies showing reduced GABA efficacy at variant receptors 1. Genetic variants in GABBR1 are also associated with methamphetamine dependence and nicotine dependence susceptibility 62.

Sources cited
1
GABBR1 forms obligatory heterodimers with GABBR2 for neuronal inhibition and de novo variants cause neurodevelopmental disorders
PMID: 36103875
2
GABBR1 modulates neurotransmitter release through G protein-coupled pathways and is associated with nicotine dependence
PMID: 19763258
3
GABBR1 regulates hematopoietic stem and progenitor cell proliferation and function
PMID: 32881992
4
GABBR1/GABBR2 pathways mediate GABA inhibition of IL-17A production in intestinal immune cells
PMID: 40033120
5
GABBR1 in dopaminergic neurons regulates locomotion termination through specific neuronal subtypes
PMID: 40108161
6
GABBR1 genetic variants are associated with methamphetamine dependence and relapse
PMID: 30143926
Disease Associationsβ“˜21
neurodevelopmental disorder with language delay and variable cognitive abnormalitiesOpen Targets
0.65Moderate
SpasticityOpen Targets
0.60Moderate
multiple sclerosisOpen Targets
0.57Moderate
RigidityOpen Targets
0.54Moderate
spinal cord injuryOpen Targets
0.53Moderate
cerebral palsyOpen Targets
0.53Moderate
neurodegenerative diseaseOpen Targets
0.52Moderate
narcolepsyOpen Targets
0.52Moderate
narcolepsy-cataplexy syndromeOpen Targets
0.49Moderate
fragile X syndromeOpen Targets
0.38Weak
Global developmental delayOpen Targets
0.38Weak
Intellectual disabilityOpen Targets
0.38Weak
Delayed speech and language developmentOpen Targets
0.38Weak
alcohol dependenceOpen Targets
0.38Weak
fibromyalgiaOpen Targets
0.37Weak
brain injuryOpen Targets
0.37Weak
autosomal dominant non-syndromic intellectual disabilityOpen Targets
0.37Weak
CataplexyOpen Targets
0.37Weak
spinal cord diseaseOpen Targets
0.37Weak
PainOpen Targets
0.34Weak
Neurodevelopmental disorder with language delay and variable cognitive abnormalitiesUniProt
Pathogenic Variants7
NM_001470.4(GABBR1):c.1591G>A (p.Gly531Ser)Pathogenic
GABBR1-related neurodevelopmental disorder|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 531
NM_001470.4(GABBR1):c.2546T>C (p.Leu849Pro)Likely pathogenic
Neurodevelopmental disorder with language delay and variable cognitive abnormalities
β˜…β˜†β˜†β˜†2024β†’ Residue 849
NM_001470.4(GABBR1):c.1190C>T (p.Ala397Val)Likely pathogenic
Intellectual disability;Motor delay;Atypical behavior;Delayed speech and language development;Global developmental delay|Neurodevelopmental disorder with language delay and variable cognitive abnormalities
β˜…β˜†β˜†β˜†2024β†’ Residue 397
NM_001470.4(GABBR1):c.1042G>C (p.Ala348Pro)Likely pathogenic
Neurofibromatosis, type 1
β˜…β˜†β˜†β˜†2023β†’ Residue 348
NM_001470.4(GABBR1):c.2018G>A (p.Gly673Asp)Likely pathogenic
Intellectual disability;Delayed speech and language development;Global developmental delay|Neurodevelopmental disorder with language delay and variable cognitive abnormalities
β˜…β˜†β˜†β˜†2022β†’ Residue 673
NM_001470.4(GABBR1):c.1603G>A (p.Ala535Thr)Likely pathogenic
Intellectual disability;Delayed speech and language development;Global developmental delay|Neurodevelopmental disorder with language delay and variable cognitive abnormalities
β˜…β˜†β˜†β˜†2022β†’ Residue 535
NM_001470.4(GABBR1):c.1104G>C (p.Glu368Asp)Likely pathogenic
Intellectual disability;Delayed speech and language development;Global developmental delay|Neurodevelopmental disorder with language delay and variable cognitive abnormalities
β˜…β˜†β˜†β˜†2022β†’ Residue 368
View on ClinVar β†—
Drug Targets7
ARBACLOFENPhase III
GABA-B receptor agonist
fragile X syndrome
ARBACLOFEN PLACARBILPhase III
GABA-B receptor agonist
fragile X syndrome
BACLOFENApproved
GABA-B receptor agonist
Spasticity
LESOGABERANPhase II
GABA-B receptor 2 agonist
gastroesophageal reflux disease
OXYBATEPhase II
GABA-B receptor agonist
opioid dependence
SGS-742Phase II
GABA-B receptor antagonist
schizophrenia
SODIUM OXYBATEApproved
GABA-B receptor agonist
Related Genes
CALCRLProtein interaction100%GNAI1Protein interaction99%RAMP2Protein interaction99%RAMP1Protein interaction96%KCNJ6Protein interaction96%KCNJ3Protein interaction96%
Tissue Expression6 tissues
Brain
100%
Ovary
98%
Bone Marrow
83%
Lung
35%
Heart
31%
Liver
10%
Gene Interaction Network
Click a node to explore
GABBR1CALCRLGNAI1RAMP2RAMP1KCNJ6KCNJ3
PROTEIN STRUCTURE
Preparing viewer…
PDB4PAS Β· 1.62 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.38Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.28 [0.21–0.38]
RankingsWhere GABBR1 stands among ~20K protein-coding genes
  • #2,971of 20,598
    Most Researched152 Β· top quartile
  • #576of 1,025
    FDA-Approved Drug Targets2
  • #3,168of 5,498
    Most Pathogenic Variants7
  • #1,806of 17,882
    Most Constrained (LOEUF)0.38 Β· top quartile
Genes detectedGABBR1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Enteric GABAergic neuron-derived Ξ³-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis.
PMID: 40033120
Nat Immunol Β· 2025
1.00
2
Variants in GABBR1 Gene Are Associated with Methamphetamine Dependence and Two Years' Relapse after Drug Rehabilitation.
PMID: 30143926
J Neuroimmune Pharmacol Β· 2018
0.90
3
The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.
PMID: 41055971
J Clin Invest Β· 2025
0.84
4
Organ-specific proteomic aging clocks predict disease and longevity across diverse populations.
PMID: 41299092
Nat Aging Β· 2026
0.80
5
Bisphenol A promotes OSCC progression via GABBR1-mediated MAPK signaling and macrophage polarization: A network toxicology based study.
PMID: 40779845
Ecotoxicol Environ Saf Β· 2025
0.70