Alternative titles; symbols
HGNC Approved Gene Symbol: GABRG3
Cytogenetic location: 15q12 Genomic coordinates (GRCh38): 15:26,971,181-27,541,984 (from NCBI)
Gamma-aminobutyric acid (GABA) receptors are a family of proteins involved in the GABAergic neurotransmission of the mammalian central nervous system. GABRG3 is a member of the GABA-A receptor gene family of heteromeric pentameric ligand-gated ion channels through which GABA, the major inhibitory neurotransmitter in the mammalian brain, acts. GABA-A receptors are the site of action of a number of important pharmacologic agents including barbiturates, benzodiazepines, and ethanol (summary by Whiting et al., 1999).
For additional general information about the GABA-A receptor gene family, see GABRA1 (137160).
Greger et al. (1995) cloned the gene for the gamma-3 subunit.
Russek and Farb (1994) stated that the GABRG3 is located on 15q11-q13 in a cluster with GABRA5 (137142) and GABRB3 (137192). Thus, there is an alpha/beta/gamma cluster of GABA receptor subunit subtype genes on 3 chromosomes, 15, 5, and 3. Russek and Farb (1994) suggested that these may have originated from chromosome 15 because the centromere of that chromosome is associated with increased amounts of satellite DNA and translocations occur more frequently around such centromeres. Thus, it can be speculated that the ancestral GABA-A receptor gene cluster formed on chromosome 15 and thereafter spawned the clusters on chromosomes 4 and 5.
Greger et al. (1995) showed that the GABRG3 gene is 35 kb from the alpha-5 subunit gene which, in turn, is about 100 kb from the beta-3 subunit locus. The latter is located at the centromeric end of the cluster and is transcribed in the opposite direction of GABRG3 and GABRA5. This orientation of the cluster is opposite that reported by Russek and Farb (1994). Greger et al. (1995) confirmed that the GABRG3 gene maps to 15q11-q13 and they verified the order of the genes by fluorescence in situ hybridization.
Using coding SNPs within the GABA receptor gene cluster on chromosome 15q11-q13, Hogart et al. (2007) demonstrated that the GABRG3, GABRB3, and GABRA5 genes were biallelically expressed in the cerebral cortex of 21 postmortem human brain samples.
Greger, V., Knoll, J. H. M., Woolf, E., Glatt, K., Tyndale, R. F., DeLorey, T. M., Olsen, R. W., Tobin, A. J., Sikela, J. M., Nakatsu, Y., Brilliant, M. H., Whiting, P. J., Lalande, M. The gamma-aminobutyric acid receptor gamma-3 subunit gene (GABRG3) is tightly linked to the alpha-5 subunit gene (GABRA5) on human chromosome 15q11-q13 and is transcribed in the same orientation. Genomics 26: 258-264, 1995. [PubMed: 7601451] [Full Text: https://doi.org/10.1016/0888-7543(95)80209-5]
Hogart, A., Nagarajan, R. P., Patzel, K. A., Yasui, D. H., Lasalle, J. M. 15q11-13 GABA(A) receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum. Molec. Genet. 16: 691-703, 2007. [PubMed: 17339270] [Full Text: https://doi.org/10.1093/hmg/ddm014]
Russek, S. J., Farb, D. H. Mapping of the beta-2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABA-A receptor isoform. Genomics 23: 528-533, 1994. [PubMed: 7851879] [Full Text: https://doi.org/10.1006/geno.1994.1539]
Whiting, P. J., Bonnert, T. P., McKernan, R. M., Farrar, S., le Bourdelles, B., Heavens, R. P., Smith, D. W., Hewson, L., Rigby, M. R., Sirinathsinghji, D. J. S., Thompson, S. A., Wafford, K. A. Molecular and functional diversity of the expanding GABA-A receptor gene family. Ann. N.Y. Acad. Sci. 868: 645-653, 1999. [PubMed: 10414349] [Full Text: https://doi.org/10.1111/j.1749-6632.1999.tb11341.x]