Aliases: GABABR1-3, GB1, GPRC3A,GABBR1
Chromosome No: 6
Chromosome Band: 6p22.1
Genetic Category: Functional-Rare single gene variant-Genetic association-Rare single gene variant/Functional
ASD Reports: 10
Recent Reports: 2
Annotated variants: 8
Associated CNVs: 4
Evidence score: 3
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Relevance to Autism
A potentially deleterious de novo missense variant in the GABBR1 gene was identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020. FENRIR prioritization of a brain-specific enhancer network in Chen et al., 2021 concluded that a de novo ASD-associated intronic variant in the GABBR1 gene (originally identified in Zhou et al., 2019) resided within an ASD-associated enhancer for which GABBR1 was the most likely target gene; experimental validation of the allele-specific regulatory effects of the enhancer for this gene by dual-luciferase assays demonstrated that the proband-specific allele resulted in significantly reduced luciferase activity compared to the sibling-specific allele (p<0.0001). A cross-trait meta-analysis of genome-wide association study on schizophrenia, bipolar disorder, autism spectrum disorder, attention deficit hyperactivity disorder, and depression samples in Wu et al., 2020 implicated GABBR1 in schizophrenia, depression, and ASD [odds ratio (OR)=464.8, Fishers P=0.002]. Previous studies had reported reduced levels of GABBR1 in post-mortem brain samples from ASD probands (Fatemi et al., 2009; Fatemi et al., 2010), as well as in subjects with schizophrenia, bipolar disorder and major depression (Fatemi et al., 2011), when compared with controls. Cediel et al., 2022 identified four individuals through GeneMatcher with de novo non-synonymous variants in the GABBR1 gene presenting with developmental delay and variable additional phenotypes, including autism spectrum disorder in one individual; functional analyses of GABBR1 variants in this study demonstrated effects on surface expression and/or GABA efficacy in transfected HEK293 cells.
Molecular Function
This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy.
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