Gene Symbol: GABRA4
Description: gamma-aminobutyric acid type A receptor alpha4 subunit
Alias: gamma-aminobutyric acid receptor subunit alpha-4, GABA(A) receptor, alpha 4, gamma-aminobutyric acid (GABA) A receptor, alpha 4, gamma-aminobutyric acid A receptor alpha 4
Species: human
Products:     GABRA4

Top Publications

  1. Ma D, Whitehead P, Menold M, Martin E, Ashley Koch A, Mei H, et al. Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism. Am J Hum Genet. 2005;77:377-88 pubmed
    ..Single-nucleotide polymorphisms (SNPs) were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35...
  2. Gupta G, Sharma L. Bacopa monnieri abrogates alcohol abstinence-induced anxiety-like behavior by regulating biochemical and Gabra1, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats. Biomed Pharmacother. 2019;111:1417-1428 pubmed publisher
    ..The expression of Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 genes of the GABAA receptors subunits in the hippocampus as well as amygdala were also examined ..
  3. Jimenez Jimenez F, Esguevillas G, Alonso Navarro H, Zurdo M, Turpín Fenoll L, Millán Pascual J, et al. Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome. Pharmacogenomics J. 2018;18:565-577 pubmed publisher
    ..polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS...
  4. Chang L, Jamain S, Lin C, Rujescu D, Tseng G, Sibille E. A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies. PLoS ONE. 2014;9:e90980 pubmed publisher
    ..neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]...
  5. Yang J, Hu Y, Xiao K, Liu X, Tan C, Wang B, et al. Transcriptome profiling reveals candidate cleft palate-related genes in cultured Chinese sturgeons (Acipenser sinensis). Gene. 2018;666:1-8 pubmed publisher
    ..In these two signal pathways, six genes (GABRA4, GS, GNS, S6K, PITX2, and BMP8) were found as candidate cleft-palate genes in Chinese sturgeon...
  6. Mo J, Kim C, Lee D, Sun W, Lee H, Kim H. Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus. J Neurochem. 2015;133:489-500 pubmed publisher
    ..with in vivo chromatin immunoprecipitation, and reveals that GABAA receptor subunit, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes, are transcriptional targets of Egr-1...
  7. Green E, Grozeva D, Moskvina V, Hamshere M, Jones I, Jones L, et al. Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:1347-9 pubmed publisher
    ..Research Diagnostic Criteria (RDC) schizoaffective disorder, bipolar type) with gene-wide significance at GABRB1, GABRA4, GABRB3, GABRA5, and GABRR3...
  8. García Martín E, Esguevillas G, Serrador M, Alonso Navarro H, Navacerrada F, Amo G, et al. Gamma-aminobutyric acid (GABA) receptors GABRA4, GABRE, and GABRQ gene polymorphisms and risk for migraine. J Neural Transm (Vienna). 2018;125:689-698 pubmed publisher
    ..the possible association of the most common single nucleotide polymorphisms (SNPs) in the GABA receptor alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) genes with the risk for migraine...
  9. Lieberman R, Kranzler H, Joshi P, Shin D, Covault J. GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures. Alcohol Clin Exp Res. 2015;39:1654-64 pubmed publisher
    ..We examined mRNA expression of chromosome 4p12 GABAA subunit genes (GABRG1, GABRA2, GABRA4, and GABRB1) in 36 human neural cell lines differentiated from iPSCs using quantitative polymerase chain reaction ..

More Information


  1. Pérez Rubio G, Pérez Rodríguez M, Fernandez Lopez J, Ramirez Venegas A, García Colunga J, Avila Moreno F, et al. SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways. Pharmacogenomics. 2016;17:1145-1158 pubmed
    ..a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA ..
  2. Deprez F, Vogt F, Floriou Servou A, Lafourcade C, Rudolph U, Tyagarajan S, et al. Partial inactivation of GABAA receptors containing the α5 subunit affects the development of adult-born dentate gyrus granule cells. Eur J Neurosci. 2016;44:2258-71 pubmed publisher
    ..transmission, as shown by deficits in proliferation, migration and dendritic development of adult-born neurons in Gabra4-null mice...
  3. Stankiewicz A, Goscik J, Dyr W, Juszczak G, Ryglewicz D, Swiergiel A, et al. Novel candidate genes for alcoholism--transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats. Pharmacol Biochem Behav. 2015;139:27-38 pubmed publisher
    ..Identified genes and processes included known mediators of ethanol response (Mx2, Fam111a, Itpr1, Gabra4, Agtr1a, LTP/LTD, renin-angiotensin signaling pathway), toxicity (Sult1c2a, Ces1, inflammatory response), as well ..
  4. Pan M, Zhou Y, Wang Y, Li L, Song Y, Hou L, et al. Screening and Identification of the Host Proteins Interacting with Toxoplasma gondii Rhoptry Protein ROP16. Front Microbiol. 2017;8:2408 pubmed publisher
    ..Two mouse proteins, Dnaja1 (DnaJ heat shock protein family member A1) and Gabra4 (gamma-aminobutyric acid A receptor, subunit alpha 4) were identified to interact with ROP16 from this screen...
  5. Fiatal S, Tóth R, Moravcsik Kornyicki Ã, Kósa Z, Sándor J, McKee M, et al. High Prevalence of Smoking in the Roma Population Seems to Have No Genetic Background. Nicotine Tob Res. 2016;18:2260-2267 pubmed publisher
    ..nucleotide polymorphisms in genes COMT, CHRNA3/4/5, CYP2A6, CTNNA3, DRD2, MAOA, KCNJ6, AGPHD1, ANKK1, TRPC7, GABRA4, and NRXN1. The distribution of scores in study populations was compared...
  6. Osechkina N, Ivanov M, Nazarov G, Batotsyrenova E, Lapina N, Babkin A, et al. Assessment of Expression of Genes Coding GABAA Receptors during Chronic and Acute Intoxication of Laboratory Rats with Ethanol. Bull Exp Biol Med. 2016;160:452-4 pubmed publisher
    ..Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times...
  7. Bekdash R, Harrison N. Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons. Brain Behav. 2015;5:e00355 pubmed publisher
    ..b>Gabra4, which encodes the α4 subunit of GABAA receptors (GABAARs), is one of a number of ARGs that show remarkable ..
  8. Iwata H, Yamamuro Y. Subregional Expression of Hippocampal Glutamatergic and GABAergic Genes in F344 Rats with Social Isolation after Weaning. Comp Med. 2016;66:4-9 pubmed
    ..In contrast, pwSI tended to decrease the expression of GABAA receptor subunit genes, and Gabra1, Gabra2, Gabra4, Gabra5, Gabrb2, Gabrg1, and Gabrg2 were all significantly decreased in expression compared with the levels in the ..
  9. Liu M, Fitzgibbon M, Wang Y, Reilly J, Qian X, O BRIEN T, et al. Ulk4 regulates GABAergic signaling and anxiety-related behavior. Transl Psychiatry. 2018;8:43 pubmed publisher
    ..Pvalb, Sst, Cck, Npy, and Nos3, as well as significant upregulation of GABA receptors, including Gabra1, Gabra3, Gabra4, Gabra5, and Gabrb3...
  10. Whiting P, Bonnert T, McKernan R, Farrar S, Le Bourdelles B, Heavens R, et al. Molecular and functional diversity of the expanding GABA-A receptor gene family. Ann N Y Acad Sci. 1999;868:645-53 pubmed
    ..The structure, function, and distribution of theta-containing receptors, and receptors containing the recently reported epsilon subunit, are described. ..
  11. Agrawal A, Pergadia M, Balasubramanian S, Saccone S, Hinrichs A, Saccone N, et al. Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerström Test for Nicotine Dependence. Addiction. 2009;104:471-7 pubmed publisher
    A previous association analysis identified polymorphisms in gamma-aminobutyric acid receptor A, subunit 4 (GABRA4) and GABRA2 to be associated with nicotine dependence, as assessed by a score of 4 or more on the Fagerström Test for ..
  12. Yocum G, Turner D, Danielsson J, Barajas M, Zhang Y, Xu D, et al. GABAA receptor ?4-subunit knockout enhances lung inflammation and airway reactivity in a murine asthma model. Am J Physiol Lung Cell Mol Physiol. 2017;313:L406-L415 pubmed publisher
    ..of a murine allergic asthma model utilizing GABAAR ?4-subunit global knockout (KO; Gabra40/0 ) mice...
  13. Sesarini C, Costa L, Grañana N, Coto M, Pallia R, Argibay P. Association between GABA(A) receptor subunit polymorphisms and autism spectrum disorder (ASD). Psychiatry Res. 2015;229:580-2 pubmed publisher
    ..significant differences in allele and genotype frequencies observed between cases and controls (rs1912960, GABRA4). Haplotype analysis: rs1912960 (GABRA4) and rs211037 (GABRG2) overrepresented in cases...
  14. Tögel M, Mossier B, Fuchs K, Sieghart W. 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. 1994;269:12993-8 pubmed
    ..These data indicate that gamma 3-subunits can combine with most alpha-subunits to form a multiplicity of GABAA receptors with distinct pharmacology. ..
  15. Lagrange A, Botzolakis E, Macdonald R. Enhanced macroscopic desensitization shapes the response of alpha4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA. J Physiol. 2007;578:655-76 pubmed
  16. Dick D, Aliev F, Latendresse S, Porjesz B, Schuckit M, Rangaswamy M, et al. How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity. Twin Res Hum Genet. 2013;16:661-9 pubmed publisher
  17. Garcia Martin E, Martinez C, Alonso Navarro H, Benito Leon J, Lorenzo Betancor O, Pastor P, et al. Gamma-aminobutyric acid GABRA4, GABRE, and GABRQ receptor polymorphisms and risk for essential tremor. Pharmacogenet Genomics. 2011;21:436-9 pubmed publisher
    ..We studied the allelic and genotype frequencies of the single nucleotide polymorphisms, such as GABRA4-L26M (Leu26Met, rs2229940), GABRE-S102A (Ser26Ala, rs1139916), and GABRQ-I478F (Ile26Phe, rs3810651), in 200 ..
  18. Inada T, Koga M, Ishiguro H, Horiuchi Y, Syu A, Yoshio T, et al. Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia. Pharmacogenet Genomics. 2008;18:317-23 pubmed publisher
    ..Redwood City, California, USA). Eight genes (ABAT, ALDH9A1, GABRA3, GABRA4, GABRB2, GABRAG3, GPHN, and SLC6A11) contained polymorphisms with gene-based corrected allelic P values of less ..
  19. Craddock N, Jones L, Jones I, Kirov G, Green E, Grozeva D, et al. Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype. Mol Psychiatry. 2010;15:146-53 pubmed publisher
    ..6 x 10(-5)) with association signals also at GABRA4, GABRB3, GABRA5 and GABRR3...
  20. Collins A, Ma D, Whitehead P, Martin E, Wright H, Abramson R, et al. Investigation of autism and GABA receptor subunit genes in multiple ethnic groups. Neurogenetics. 2006;7:167-74 pubmed
    ..of noncoding single nucleotide polymorphisms (SNPs) within a GABA receptor subunit gene on chromosome 4, GABRA4, and interaction between SNPs in GABRA4 and GABRB1 (also on chromosome 4), within Caucasian autism patients...
  21. Mu W, Cheng Q, Yang J, Burt D. Alternative splicing of the GABA(A) receptor alpha 4 subunit creates a severely truncated mRNA. Brain Res Bull. 2002;58:447-54 pubmed
    ..Thus, the truncated alpha 4 N-terminus may play a post-translational regulatory role in intracellular folding/glycosylation/assembly of the alpha 4 subunit. ..
  22. Kwon W, Kim H, Jeong J, Sung Y, Choi M, Park S, et al. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice. FASEB J. 2018;32:390-403 pubmed publisher
    ..The expression of GABA receptor subunits (Gabra2 and Gabra4) fluctuated in the prefrontal cortex and hippocampus...
  23. Saccone S, Hinrichs A, Saccone N, Chase G, Konvicka K, Madden P, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet. 2007;16:36-49 pubmed
    ..Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found ..
  24. Abramian A, Comenencia Ortiz E, Modgil A, Vien T, Nakamura Y, Moore Y, et al. Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Proc Natl Acad Sci U S A. 2014;111:7132-7 pubmed publisher
  25. Agrawal A, Pergadia M, Saccone S, Hinrichs A, Lessov Schlaggar C, Saccone N, et al. Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case-control study. Addiction. 2008;103:1027-38 pubmed publisher
    ..We found evidence for association between four SNPs in GABRA4, two SNPs in GABRA2 and one SNP in GABRE with nicotine dependence...
  26. Maldonado Avilés J, Curley A, Hashimoto T, Morrow A, Ramsey A, O DONNELL P, et al. Altered markers of tonic inhibition in the dorsolateral prefrontal cortex of subjects with schizophrenia. Am J Psychiatry. 2009;166:450-9 pubmed publisher
  27. Yang W, Drewe J, Lan N. Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site. Eur J Pharmacol. 1995;291:319-25 pubmed
    ..Our study thus suggests that this subpopulation of diazepam-insensitive GABAA receptors may be composed of alpha 4 beta 2 gamma 2L subunits. ..
  28. Ren H, Guan L, Zhao L, Lin Y, Wang Y, Yang Z, et al. Contribution of genes in the GABAergic pathway to bipolar disorder and its executive function deficit in the Chinese Han population. Am J Med Genet B Neuropsychiatr Genet. 2017;: pubmed publisher
    ..For three SNPs, rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, their allele frequencies were significantly different between patients and ..
  29. Maguire E, Macpherson T, Swinny J, Dixon C, Herd M, Belelli D, et al. Tonic inhibition of accumbal spiny neurons by extrasynaptic ?4?? GABAA receptors modulates the actions of psychostimulants. J Neurosci. 2014;34:823-38 pubmed publisher
    ..Therefore, ?4?? GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors. ..
  30. Kumar S, Sieghart W, Morrow A. 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. 2002;82:110-7 pubmed
    ..These results suggest that PKCgamma may be involved in GABA(A) receptor adaptations following chronic ethanol consumption. ..
  31. Kumar R, Lumsden A, Ciclitira P, Ellis H, Laurie G. Human genome search in celiac disease using gliadin cDNA as probe. J Mol Biol. 2000;300:1155-67 pubmed
    ..Glutamine to glutamic acid or other mutation within such epitopes followed by injury or infection-related release could explain enhanced disease susceptibility in affected families. ..
  32. Al Safar H, Cordell H, Jafer O, Anderson D, Jamieson S, Fakiola M, et al. A genome-wide search for type 2 diabetes susceptibility genes in an extended Arab family. Ann Hum Genet. 2013;77:488-503 pubmed publisher
    ..030) and rs2055942 (Padj-agesex=0.022) at COX7B2/GABRA4 did, in addition to a trend distally at KCTD8 (rs4695718: Padj-agesex=0.096)...
  33. McLean P, Farb D, Russek S. 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. 1995;26:580-6 pubmed
    ..Here, we report that the alpha 4 gene (GABRA4) maps to human chromosome 4p14-q12, defining a cluster comprising the alpha 2, alpha 4, beta 1, and gamma 1 genes...
  34. Griswold A, van Booven D, Cuccaro M, Haines J, Gilbert J, Pericak Vance M. Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder. Neurogenetics. 2018;19:17-26 pubmed publisher
    ..Genetic associations of common variants in GABA receptor subunits, in particular GABRA4 on chromosome 4p12, with ASD have been replicated by several studies...
  35. Adams M, McCrone S. SRD5A1 genotype frequency differences in women with mild versus severe premenstrual symptoms. Issues Ment Health Nurs. 2012;33:101-8 pubmed publisher
    ..steroid-5-alpha-reductase, alpha polypeptide 1 (SRD5A1) and gamma-aminobutyric acid receptor subunit alpha-4 (GABRA4)...