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Gene Review

GAD1  -  glutamate decarboxylase 1 (brain, 67kDa)

Homo sapiens

Synonyms: 67 kDa glutamic acid decarboxylase, CPSQ1, GAD, GAD-67, GAD67, ...
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Disease relevance of GAD1


Psychiatry related information on GAD1


High impact information on GAD1


Chemical compound and disease context of GAD1


Biological context of GAD1

  • Three adjacent SNPs in the 5' upstream region of GAD1 showed a positive pairwise association with illness in these families (P=0.022-0.057) [18].
  • In each family, the affected siblings exhibited different genotypes for the GAD2 gene; in two families the GAD1 genotype was disparate [19].
  • The GAD1 gene was mapped to human chromosome 2q31 and to mouse chromosome 2D in a known region of conservation between human and mouse [20].
  • Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genes [21].
  • We systematically screened GAD1 exons, flanking intronic sequences, and the promoter sequence for polymorphisms in 16 BPAD patients and five controls from Denmark [7].

Anatomical context of GAD1


Associations of GAD1 with chemical compounds


Physical interactions of GAD1

  • In this study we aimed to determine whether the substitution of GAD65 with GAD67 amino acids would affect the binding of conformation-dependent GAD65 autoantibodies [30].

Co-localisations of GAD1


Regulatory relationships of GAD1

  • In the human DLPFC, GAD65 mRNA was found to be expressed significantly less than the message for GAD67, approximately 16% of that observed for GAD67 [32].
  • To consolidate and expand on previous findings that, in the cortex of schizophrenia (SZ) brains, glutamic acid decarboxylase 67 (GAD67) expression is down-regulated whereas that of DNMT1 is up-regulated, we studied both parameters in Brodmann's area (BA) 9 from the McLean 66 Cohort Collection (Harvard Brain Tissue Resource Center, Belmont, MA) [33].
  • In the patients with newly diagnosed type 1 diabetes, anti-glutamate decarboxylase (GAD)-reactivity was found in the subpopulation of lymphocytes expressing gut-associated homing receptor alpha 4 beta 7 [34].

Other interactions of GAD1


Analytical, diagnostic and therapeutic context of GAD1

  • In this report, we determined the role of cysteine residues in the recombinant human 65-kDa GAD isoform (hGAD65) and 67-kDa GAD isoform (hGAD67), using a combination of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and site-directed mutagenesis [28].
  • In an effort to understand the molecular mechanism of gibberellin (GA) action, we have cloned and performed an initial characterization of three cDNAs (GAD1, 2, and 3) which correspond to RNAs that become less abundant by 2 h after treatment of tomato (Lycopersicon esculentum Mill.) shoot tissue with gibberellic acid (GA3) [37].
  • An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001) [3].
  • Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1 [40].
  • In 18 subjects with diabetic oral glucose tolerance test, GAD65 autoantibody concentrations were higher than in those with normal oral glucose tolerance test (p = 0.02) [4].


  1. Molecular characterization of a disease associated conformational epitope on GAD65 recognised by a human monoclonal antibody b96.11. Fenalti, G., Hampe, C.S., O'connor, K., Banga, J.P., Mackay, I.R., Rowley, M.J., El-Kabbani, O. Mol. Immunol. (2007) [Pubmed]
  2. Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders. Lynex, C.N., Carr, I.M., Leek, J.P., Achuthan, R., Mitchell, S., Maher, E.R., Woods, C.G., Bonthon, D.T., Markham, A.F. BMC neurology [electronic resource]. (2004) [Pubmed]
  3. Prevalence of autoantibodies to the 65- and 67-kD isoforms of glutamate decarboxylase in insulin-dependent diabetes mellitus. Seissler, J., Amann, J., Mauch, L., Haubruck, H., Wolfahrt, S., Bieg, S., Richter, W., Holl, R., Heinze, E., Northemann, W. J. Clin. Invest. (1993) [Pubmed]
  4. Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index. Rolandsson, O., Hägg, E., Hampe, C., Sullivan, E.P., Nilsson, M., Jansson, G., Hallmans, G., Lernmark, A. Diabetologia (1999) [Pubmed]
  5. Association between nonsyndromic cleft lip with or without cleft palate and the glutamic acid decarboxylase 67 gene in the Japanese population. Kanno, K., Suzuki, Y., Yamada, A., Aoki, Y., Kure, S., Matsubara, Y. Am. J. Med. Genet. A (2004) [Pubmed]
  6. Association between glutamic acid decarboxylase genes and anxiety disorders, major depression, and neuroticism. Hettema, J.M., An, S.S., Neale, M.C., Bukszar, J., van den Oord, E.J., Kendler, K.S., Chen, X. Mol. Psychiatry (2006) [Pubmed]
  7. Mutational screening and association study of glutamate decarboxylase 1 as a candidate susceptibility gene for bipolar affective disorder and schizophrenia. Lundorf, M.D., Buttenschøn, H.N., Foldager, L., Blackwood, D.H., Muir, W.J., Murray, V., Pelosi, A.J., Kruse, T.A., Ewald, H., Mors, O. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2005) [Pubmed]
  8. Mutation screen of the glutamate decarboxylase-67 gene and haplotype association to unipolar depression. Lappalainen, J., Sanacora, G., Kranzler, H.R., Malison, R., Hibbard, E.S., Price, L.H., Krystal, J., Gelernter, J. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  9. S-adenosyl methionine and DNA methyltransferase-1 mRNA overexpression in psychosis. Guidotti, A., Ruzicka, W., Grayson, D.R., Veldic, M., Pinna, G., Davis, J.M., Costa, E. Neuroreport (2007) [Pubmed]
  10. Differential effects of agonal status on measurements of GABA and glutamate decarboxylase in human post-mortem brain tissue from control and Huntington's chorea subjects. Spokes, E.G., Garrett, N.J., Iversen, L.L. J. Neurochem. (1979) [Pubmed]
  11. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Kaufman, D.L., Clare-Salzler, M., Tian, J., Forsthuber, T., Ting, G.S., Robinson, P., Atkinson, M.A., Sercarz, E.E., Tobin, A.J., Lehmann, P.V. Nature (1993) [Pubmed]
  12. Brain glutamate decarboxylase cloned in lambda gt-11: fusion protein produces gamma-aminobutyric acid. Kaufman, D.L., McGinnis, J.F., Krieger, N.R., Tobin, A.J. Science (1986) [Pubmed]
  13. High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Okada, Y., Taniguchi, H., Schimada, C. Science (1976) [Pubmed]
  14. Replacement of methionine-161 with threonine eliminates a major by-product of human glutamate decarboxylase 65-kDa variant expression in Escherichia coli. Santos, J., Antón, E.A., Buslje, C.M., Valdez, S.N., Villanueva, A.L., Sica, M., Iacono, R., Maffia, P., Poskus, E., Ermácora, M.R. Biotechnol. Appl. Biochem. (2000) [Pubmed]
  15. Characterization of the rat GAD67 gene promoter reveals elements important for basal transcription and glucose responsiveness. Pedersen, A.A., Videbaek, N., Skak, K., Petersen, H.V., Michelsen, B.K. DNA Seq. (2001) [Pubmed]
  16. A glutamate decarboxylase system protects Listeria monocytogenes in gastric fluid. Cotter, P.D., Gahan, C.G., Hill, C. Mol. Microbiol. (2001) [Pubmed]
  17. Effects of nigrostriatal denervation and L-dopa therapy on the GABAergic neurons in the striatum in MPTP-treated monkeys and Parkinson's disease: an in situ hybridization study of GAD67 mRNA. Levy, R., Herrero, M.T., Ruberg, M., Villares, J., Faucheux, B., Guridi, J., Guillen, J., Luquin, M.R., Javoy-Agid, F., Obeso, J.A. Eur. J. Neurosci. (1995) [Pubmed]
  18. GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Addington, A.M., Gornick, M., Duckworth, J., Sporn, A., Gogtay, N., Bobb, A., Greenstein, D., Lenane, M., Gochman, P., Baker, N., Balkissoon, R., Vakkalanka, R.K., Weinberger, D.R., Rapoport, J.L., Straub, R.E. Mol. Psychiatry (2005) [Pubmed]
  19. Glutamate decarboxylase is not genetically linked to pyridoxine-dependent seizures. Battaglioli, G., Rosen, D.R., Gospe, S.M., Martin, D.L. Neurology (2000) [Pubmed]
  20. Mapping of glutamic acid decarboxylase (GAD) genes. Edelhoff, S., Grubin, C.E., Karlsen, A.E., Alder, D.A., Foster, D., Disteche, C.M., Lernmark, A. Genomics (1993) [Pubmed]
  21. Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genes. Rabionet, R., Jaworski, J.M., Ashley-Koch, A.E., Martin, E.R., Sutcliffe, J.S., Haines, J.L., Delong, G.R., Abramson, R.K., Wright, H.H., Cuccaro, M.L., Gilbert, J.R., Pericak-Vance, M.A. Neurosci. Lett. (2004) [Pubmed]
  22. Increased expression of GAD65 and GABA in pancreatic beta-cells impairs first-phase insulin secretion. Shi, Y., Kanaani, J., Menard-Rose, V., Ma, Y.H., Chang, P.Y., Hanahan, D., Tobin, A., Grodsky, G., Baekkeskov, S. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  23. Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase. Kelly, C.D., Edwards, Y., Johnstone, A.P., Harfst, E., Nógrádi, A., Nussey, S.S., Povey, S., Carter, N.D. Ann. Hum. Genet. (1992) [Pubmed]
  24. Demonstration of GAD-65 as the main immunogenic isoform of glutamate decarboxylase in type 1 diabetes and determination of autoantibodies using a radioligand produced by eukaryotic expression. Velloso, L.A., Kämpe, O., Hallberg, A., Christmanson, L., Betsholtz, C., Karlsson, F.A. J. Clin. Invest. (1993) [Pubmed]
  25. Two isoforms of glutamate decarboxylase: why? Soghomonian, J.J., Martin, D.L. Trends Pharmacol. Sci. (1998) [Pubmed]
  26. Autoreactive epitopes defined by diabetes-associated human monoclonal antibodies are localized in the middle and C-terminal domains of the smaller form of glutamate decarboxylase. Richter, W., Shi, Y., Baekkeskov, S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  27. Linkage disequilibrium between GABRB3 gene and nonsyndromic familial cleft lip with or without cleft palate. Scapoli, L., Martinelli, M., Pezzetti, F., Carinci, F., Bodo, M., Tognon, M., Carinci, P. Hum. Genet. (2002) [Pubmed]
  28. Structural and functional analysis of cysteine residues in human glutamate decarboxylase 65 (GAD65) and GAD67. Wei, J., Wu, J.Y. J. Neurochem. (2005) [Pubmed]
  29. A novel method for expression and large-scale production of human brain l-glutamate decarboxylase. Davis, K.M., Foos, T., Bates, C.S., Tucker, E., Hsu, C.C., Chen, W., Jin, H., Tyburski, J.B., Schloss, J.V., Tobin, A.J., Wu, J.Y. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  30. Conformation-dependent GAD65 autoantibodies in diabetes. Luo, D., Gilliam, L.K., Greenbaum, C., Bekris, L., Hampe, C.S., Daniels, T., Richter, W., Marcovina, S.M., Rolandsson, O., Landin-Olsson, M., Kockum, I., Lernmark, A. Diabetologia (2004) [Pubmed]
  31. Targeting of the 67-kDa isoform of glutamic acid decarboxylase to intracellular organelles is mediated by its interaction with the NH2-terminal region of the 65-kDa isoform of glutamic acid decarboxylase. Dirkx, R., Thomas, A., Li, L., Lernmark, A., Sherwin, R.S., De Camilli, P., Solimena, M. J. Biol. Chem. (1995) [Pubmed]
  32. GAD67 and GAD65 mRNA and protein expression in cerebrocortical regions of elderly patients with schizophrenia. Dracheva, S., Elhakem, S.L., McGurk, S.R., Davis, K.L., Haroutunian, V. J. Neurosci. Res. (2004) [Pubmed]
  33. In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Veldic, M., Guidotti, A., Maloku, E., Davis, J.M., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  34. The role of the gut in beta-cell autoimmunity and type 1 diabetes: a hypothesis. Vaarala, O. Pediatric diabetes. (2000) [Pubmed]
  35. A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31. Cormier-Daire, V., Dagoneau, N., Nabbout, R., Burglen, L., Penet, C., Soufflet, C., Desguerre, I., Munnich, A., Dulac, O. Am. J. Hum. Genet. (2000) [Pubmed]
  36. Estrogen produced in cultured hippocampal neurons is a functional regulator of a GABAergic machinery. Ikeda, T., Matsuki, N., Yamada, M.K. J. Neurosci. Res. (2006) [Pubmed]
  37. Gibberellins regulate the abundance of RNAs with sequence similarity to proteinase inhibitors, dioxygenases and dehydrogenases. Jacobsen, S.E., Olszewski, N.E. Planta (1996) [Pubmed]
  38. Oxygen-induced seizures and inhibition of human glutamate decarboxylase and porcine cysteine sulfinic acid decarboxylase by oxygen and nitric oxide. Davis, K., Foos, T., Wu, J.Y., Schloss, J.V. J. Biomed. Sci. (2001) [Pubmed]
  39. Mutation and polymorphic marker analyses of 65K- and 67K-glutamate decarboxylase genes in two families with pyridoxine-dependent epilepsy. Kure, S., Sakata, Y., Miyabayashi, S., Takahashi, K., Shinka, T., Matsubara, Y., Hoshino, H., Narisawa, K. J. Hum. Genet. (1998) [Pubmed]
  40. Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Karlsen, A.E., Hagopian, W.A., Grubin, C.E., Dube, S., Disteche, C.M., Adler, D.A., Bärmeier, H., Mathewes, S., Grant, F.J., Foster, D. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
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