Human Gene Module / Chromosome 15 / GABRG3

GABRG3gamma-aminobutyric acid type A receptor gamma3 subunit

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
8 / 9
Rare Variants / Common Variants
5 / 4
Aliases
-
Associated Syndromes
-
Genetic Category
Genetic Association
Chromosome Band
15q12
Associated Disorders
-
Relevance to Autism

Nominal association between the GABRG3 gene and ASD has been observed in a Caucasian cohort (Menold et al., 2001) and, more recently, a Chinese ASD cohort (Wang et al., 2018); however, other studies have failed to show association between this gene and ASD (McCauley et al., 2004; Ma et al., 2005; Tochigi et al., 2007; Kelemenova et al., 2010; Mahdavi et al., 2018). Yang et al., 2017 found association between the GABRG3 SNP rs208129 and symptom-based phenotypes, as evaluated by CARS and ABC, in a cohort of 99 Chinese Han children and adolescents with ASD. Wang et al., identified a rare missense variant that was predicted to be deleterious (p.Val233Met) that was statistically enriched in Han Chinese ASD cases compared to controls (9/512 ASD cases vs. 2/575 controls; p = 0.020).

Molecular Function

This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site.

Reports related to GABRG3 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. Menold MM , et al. (2002) Yes -
2 Negative Association A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism. McCauley JL , et al. (2004) Yes -
3 Negative Association Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism. Ma DQ , et al. (2005) Yes -
4 Support An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as ris... Ashley-Koch AE , et al. (2006) No -
5 Negative Association No evidence for significant association between GABA receptor genes in chromosome 15q11-q13 and autism in a Japanese population. Tochigi M , et al. (2007) Yes -
6 Negative Association Polymorphisms of candidate genes in Slovak autistic patients. Kelemenova S , et al. (2010) Yes -
7 Positive Association GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic sp... Yang S , et al. (2017) Yes -
8 Negative Association Meta-Analysis of the Association between GABA Receptor Polymorphisms and Autism Spectrum Disorder (ASD). Mahdavi M , et al. (2018) Yes -
9 Positive Association Association study and mutation sequencing of genes on chromosome 15q11-q13 identified GABRG3 as a susceptibility gene for autism in Chinese Han pop... Wang L , et al. (2018) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.381C>T p.Pro365Ser missense_variant De novo - - 30108208 Wang L , et al. (2018)
c.697G>A p.Val233Met missense_variant De novo - - 30108208 Wang L , et al. (2018)
c.381C>T p.Pro365Ser missense_variant Familial Paternal - 30108208 Wang L , et al. (2018)
c.697G>A p.Val233Met missense_variant Familial Maternal - 30108208 Wang L , et al. (2018)
c.697G>A p.Val233Met missense_variant Familial Paternal - 30108208 Wang L , et al. (2018)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.203-18722C>A - intron_variant - - - 30108208 Wang L , et al. (2018)
c.574+81T>C - intron_variant - - - 12092907 Menold MM , et al. (2002)
c.271-147049A>T - intron_variant - - - 28607477 Yang S , et al. (2017)
c.507T>C p.(=) synonymous_variant - - - 12092907 Menold MM , et al. (2002)
CNVs associated with GABRG3(1 CNVs)
15q12 9 Deletion-Duplication 16  /  18
Submit New Gene

Report an Error