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Gamma-aminobutyric acid (GABA) A receptor, alpha 5
Symbols GABRA5; MGC138184
External IDs OMIM137142 MGI95617 HomoloGene20219 GeneCards: GABRA5 Gene
Species Human Mouse
Entrez 2558 110886
Ensembl n/a ENSMUSG00000055078
UniProt n/a O88964
RefSeq (mRNA) NM_000810 NM_176942
RefSeq (protein) NP_000801 NP_795916
Location (UCSC) n/a Chr 7:
57.28 - 57.38 Mb
PubMed search [1] [2]

Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.[1][2]



GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described.[1]

Subunit selective ligands

Recent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amnesia. Inverse agonists at this subunit have nootropic effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease.



Inverse agonists

See also


  1. ^ a b "Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5".  
  2. ^ Wingrove P, Hadingham K, Wafford K, Kemp JA, Ragan CI, Whiting P (February 1992). "Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit". Biochem. Soc. Trans. 20 (1): 18S. PMID 1321750.  
  3. ^ Ballard TM, Knoflach F, Prinssen E, et al. (2008). "RO4938581, a novel cognitive enhancer acting at GABA(A) alpha5 subunit-containing receptors". Psychopharmacology (Berl.) 202: 207. doi:10.1007/s00213-008-1357-7. PMID 18936916.  
  4. ^ van Niel MB, Wilson K, Adkins CH, et al. (2005). "A new pyridazine series of GABAA alpha5 ligands". J. Med. Chem. 48 (19): 6004–11. doi:10.1021/jm050249x. PMID 16162003.  
  5. ^ Chambers MS, Atack JR, Bromidge FA, et al. (2002). "6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists". J. Med. Chem. 45 (6): 1176–9. doi:10.1021/jm010471b. PMID 11881985.  
  6. ^ Chambers MS, Atack JR, Broughton HB, et al. (2003). "Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition". J. Med. Chem. 46 (11): 2227–40. doi:10.1021/jm020582q. PMID 12747794.  
  7. ^ Savić MM, Clayton T, Furtmüller R, et al. (2008). "PWZ-029, a compound with moderate inverse agonist functional selectivity at GABA(A) receptors containing alpha5 subunits, improves passive, but not active, avoidance learning in rats". Brain Res. 1208: 150–9. doi:10.1016/j.brainres.2008.02.020. PMID 18394590.  

Further reading

  • Delong R (2007). "GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder: a proposed endophenotype with parent-of-origin and gain-of-function features,with or without oculocutaneous albinism.". Autism : the international journal of research and practice 11 (2): 135–47. doi:10.1177/1362361307075705. PMID 17353214.  
  • Otani K, Ujike H, Tanaka Y, et al. (2005). "The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder.". Neurosci. Lett. 381 (1-2): 108–13. doi:10.1016/j.neulet.2005.02.010. PMID 15882799.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.  
  • Chou KC (2004). "Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5.". Biochem. Biophys. Res. Commun. 316 (3): 636–42. doi:10.1016/j.bbrc.2004.02.098. PMID 15033447.  
  • 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): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Ritchie RJ, Mattei MG, Lalande M (1998). "A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications.". Hum. Mol. Genet. 7 (8): 1253–60. doi:10.1093/hmg/7.8.1253. PMID 9668167.  
  • Kim Y, Glatt H, Xie W, et al. (1997). "Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region.". Genomics 42 (3): 378–87. doi:10.1006/geno.1997.4770. PMID 9205108.  
  • Glatt K, Glatt H, Lalande M (1997). "Structure and organization of GABRB3 and GABRA5.". Genomics 41 (1): 63–9. doi:10.1006/geno.1997.4639. PMID 9126483.  
  • Knoll JH, Sinnett D, Wagstaff J, et al. (1993). "FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions.". Hum. Mol. Genet. 2 (2): 183–9. doi:10.1093/hmg/2.2.183. PMID 8388764.  
  • Russek SJ, Farb DH (1995). "Mapping of the beta 2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABAA receptor isoform.". Genomics 23 (3): 528–33. doi:10.1006/geno.1994.1539. PMID 7851879.  
  • Glatt KA, Sinnett D, Lalande M (1993). "Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13.". Hum. Mol. Genet. 1 (5): 348. doi:10.1093/hmg/1.5.348. PMID 1338907.  
  • Wingrove P, Hadingham K, Wafford K, et al. (1992). "Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit.". Biochem. Soc. Trans. 20 (1): 18S. PMID 1321750.  

External links

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


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