GABRA4

Protein-coding gene in the species Homo sapiens
GABRA4
Identifiers
AliasesGABRA4, gamma-aminobutyric acid type A receptor alpha4 subunit, gamma-aminobutyric acid type A receptor subunit alpha4
External IDsOMIM: 137141 MGI: 95616 HomoloGene: 631 GeneCards: GABRA4
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for GABRA4
Genomic location for GABRA4
Band4p12Start46,918,900 bp[1]
End46,993,581 bp[1]
Gene location (Mouse)
Chromosome 5 (mouse)
Chr.Chromosome 5 (mouse)[2]
Chromosome 5 (mouse)
Genomic location for GABRA4
Genomic location for GABRA4
Band5|5 C3.1-C3.2Start71,569,749 bp[2]
End71,658,308 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • postcentral gyrus

  • entorhinal cortex

  • superior frontal gyrus

  • middle temporal gyrus

  • Brodmann area 23

  • nucleus accumbens

  • endothelial cell

  • caudate nucleus

  • putamen

  • prefrontal cortex
Top expressed in
  • lateral geniculate nucleus

  • medial dorsal nucleus

  • medial geniculate nucleus

  • olfactory tubercle

  • primary motor cortex

  • cingulate gyrus

  • piriform cortex

  • nucleus accumbens

  • globus pallidus

  • Region I of hippocampus proper
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
SpeciesHumanMouse
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 MbChr 5: 71.57 – 71.66 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

A research study compared wild-type to knockout GABRA4 gene in mice. It was determined that the elimination of the GABRA4 gene displayed characteristics that are associated with autism spectrum disorder (ASD). These include increased spatial cognition and decreased social engagement, unlike the wild-type mice. A hippocampal transcriptome analysis was profiled on knockout mice, showing the increased activity of N-methyl-D-aspartate receptors. This plays a role in consciousness and learning resulting in those characteristics.[7]

See also

  • GABAA receptor

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109158 – Ensembl, May 2017
  2. ^ a b c 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 (Aug 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. ^ a b "Entrez Gene: GABRA4 gamma-aminobutyric acid (GABA) A receptor, alpha 4".
  7. ^ Fan C, Gao Y, Liang G, Huang L, Wang J, Yang X, Shi Y, Dräger UC, Zhong M, Gao TM, Yang X (December 2020). "Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy | Molecular Autism". Molecular Autism. 11 (1): 13. doi:10.1186/s13229-020-0318-9. PMC 7007694. PMID 32033586. Retrieved 2022-05-12.

Further reading

  • Tögel M, Mossier B, Fuchs K, Sieghart W (1994). "gamma-Aminobutyric acidA receptors displaying association of gamma 3-subunits with beta 2/3 and different alpha-subunits exhibit unique pharmacological properties". J. Biol. Chem. 269 (17): 12993–12998. doi:10.1016/S0021-9258(18)99974-6. PMID 8175718.
  • Yang W, Drewe JA, Lan NC (1996). "Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site". Eur. J. Pharmacol. 291 (3): 319–325. doi:10.1016/0922-4106(95)90072-1. PMID 8719416.
  • Kumar R, Lumsden A, Ciclitira PJ, et al. (2000). "Human genome search in celiac disease using gliadin cDNA as probe". J. Mol. Biol. 300 (5): 1155–1167. doi:10.1006/jmbi.2000.3927. PMID 10903861.
  • Kumar S, Sieghart W, Morrow AL (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". J. Neurochem. 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 (2002). "Alternative splicing of the GABA(A) receptor alpha 4 subunit creates a severely truncated mRNA". Brain Res. Bull. 58 (5): 447–454. doi:10.1016/S0361-9230(02)00816-X. PMID 12242096. S2CID 140209801.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
  • Ma DQ, Whitehead PL, Menold MM, et al. (2006). "Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism". Am. J. Hum. Genet. 77 (3): 377–388. doi:10.1086/433195. PMC 1226204. PMID 16080114.
  • Collins AL, Ma D, Whitehead PL, et al. (2007). "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 (2007). "Enhanced macroscopic desensitization shapes the response of alpha4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA". J. Physiol. 578 (Pt 3): 655–676. doi:10.1113/jphysiol.2006.122135. PMC 2151343. PMID 17124266.

External links

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

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GABA receptor modulators
Ionotropic
GABAATooltip γ-Aminobutyric acid A receptor
GABAA-ρTooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABABTooltip γ-Aminobutyric acid B receptor
See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators
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