GABRA4

GABRA4
Identifiers
Aliases	GABRA4 , gamma-aminobutyric acid type A receptor alpha4 subunit, gamma-aminobutyric acid type A receptor subunit alpha4
External IDs	OMIM: 137141; MGI: 95616; HomoloGene: 631; GeneCards: GABRA4; OMA:GABRA4 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4p12 Start 46,918,900 bp [1] End 46,993,581 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 C3.1-C3.2 Start 71,569,749 bp [2] End 71,658,308 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in postcentral gyrus entorhinal cortex buccal mucosa cell superior frontal gyrus middle temporal gyrus Brodmann area 23 lateral nuclear group of thalamus nucleus accumbens endothelial cell caudate nucleus Top expressed in lateral geniculate nucleus medial dorsal nucleus medial geniculate nucleus olfactory tubercle primary motor cortex cingulate gyrus piriform cortex anterior amygdaloid area nucleus accumbens globus pallidus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ion channel activity benzodiazepine receptor activity chloride channel activity extracellular ligand-gated ion channel activity GABA-A receptor activity transmembrane signaling receptor activity inhibitory extracellular ligand-gated ion channel activity GABA-gated chloride ion channel activity transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential Cellular component integral component of membrane GABA-A receptor complex postsynaptic membrane membrane synapse integral component of plasma membrane chloride channel complex cell junction plasma membrane GABA-ergic synapse integral component of postsynaptic specialization membrane dendrite membrane neuron projection postsynapse Biological process gamma-aminobutyric acid signaling pathway chloride transmembrane transport ion transport regulation of response to drug central nervous system development chloride transport ion transmembrane transport signal transduction chemical synaptic transmission regulation of membrane potential nervous system process synaptic transmission, GABAergic regulation of postsynaptic membrane potential Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2557 14397 Ensembl ENSG00000109158 ENSMUSG00000029211 UniProt P48169 Q9D6F4 RefSeq (mRNA) NM_000809 NM_001204266 NM_001204267 NM_010251 RefSeq (protein) NP_000800 NP_001191195 NP_001191196 NP_034381 NP_001345970 NP_001345972 NP_001345973 NP_001345974 NP_001345975 NP_001345976 NP_001345977 NP_001345979 Location (UCSC) Chr 4: 46.92 – 46.99 Mb Chr 5: 71.57 – 71.66 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Gamma-aminobutyric acid receptor subunit alpha-4 is a protein that in humans is encoded by the GABRA4 gene. ^{[5] [6]}

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. At least 16 distinct subunits of GABA-A receptors have been identified. ^[6]

Research

A study in mice compared wild-type animals with those lacking the Gabra4 gene. Gabra4 knockout mice exhibited behavioral alterations relative to wild-type controls, including enhanced performance in spatial learning tasks and reduced social interaction, features that have been described as relevant to autism spectrum disorder–associated phenotypes in animal models. Transcriptomic analysis of hippocampal tissue from knockout mice identified altered gene expression consistent with increased activity of N-methyl-D-aspartate (NMDA) receptor–related signaling pathways, which are involved in synaptic plasticity, learning, and neuronal excitability. ^[7]

See also

• GABA_A receptor

References

1. GRCh38: Ensembl release 89: ENSG00000109158 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029211 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. McLean PJ, Farb DH, Russek SJ (April 1995). "Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster". Genomics. 26 (3): 580–586. doi: 10.1016/0888-7543(95)80178-O . PMID   7607683.
6. "Entrez Gene: GABRA4 gamma-aminobutyric acid (GABA) A receptor, alpha 4".
7. Fan C, Gao Y, Liang G, Huang L, Wang J, Yang X, et al. (February 2020). "Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy". Molecular Autism. 11 (1) 13. doi: 10.1186/s13229-020-0318-9 . PMC   7007694 . PMID   32033586.

Further reading

• Tögel M, Mossier B, Fuchs K, Sieghart W (April 1994). "gamma-Aminobutyric acidA receptors displaying association of gamma 3-subunits with beta 2/3 and different alpha-subunits exhibit unique pharmacological properties". The Journal of Biological Chemistry. 269 (17): 12993–12998. doi: 10.1016/S0021-9258(18)99974-6 . PMID   8175718.
• Yang W, Drewe JA, Lan NC (November 1995). "Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site". European Journal of Pharmacology. 291 (3): 319–325. doi:10.1016/0922-4106(95)90072-1. PMID   8719416.
• Kumar R, Lumsden A, Ciclitira PJ, Ellis HJ, Laurie GW (July 2000). "Human genome search in celiac disease using gliadin cDNA as probe". Journal of Molecular Biology. 300 (5): 1155–1167. doi:10.1006/jmbi.2000.3927. PMID   10903861.
• Kumar S, Sieghart W, Morrow AL (July 2002). "Association of protein kinase C with GABA(A) receptors containing alpha1 and alpha4 subunits in the cerebral cortex: selective effects of chronic ethanol consumption". Journal of Neurochemistry. 82 (1): 110–117. doi:10.1046/j.1471-4159.2002.00943.x. PMID   12091471. S2CID   82745932.
• Mu W, Cheng Q, Yang J, Burt DR (September 2002). "Alternative splicing of the GABA(A) receptor alpha 4 subunit creates a severely truncated mRNA". Brain Research Bulletin. 58 (5): 447–454. doi:10.1016/S0361-9230(02)00816-X. PMID   12242096. S2CID   140209801.
• Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley-Koch AE, Mei H, et al. (September 2005). "Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism". American Journal of Human Genetics. 77 (3): 377–388. doi:10.1086/433195. PMC   1226204 . PMID   16080114.
• Collins AL, Ma D, Whitehead PL, Martin ER, Wright HH, Abramson RK, et al. (July 2006). "Investigation of autism and GABA receptor subunit genes in multiple ethnic groups". Neurogenetics. 7 (3): 167–174. doi:10.1007/s10048-006-0045-1. PMC   1513515 . PMID   16770606.
• Lagrange AH, Botzolakis EJ, Macdonald RL (February 2007). "Enhanced macroscopic desensitization shapes the response of alpha4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA". The Journal of Physiology. 578 (Pt 3): 655–676. doi:10.1113/jphysiol.2006.122135. PMC   2151343 . PMID   17124266.

External links

• GABRA4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.