TGM6
TGM6 encodes transglutaminase 6 (TG6), a transglutaminase-family enzyme that catalyzes post-translational modification of glutamine residues, including isopeptide-bond formation, esterification, and deamidation[1]. Mechanistically, TG6 is regulated by Ca2+ and guanine nucleotides, and mouse studies show abundant TG6 mRNA and protein expression in the central nervous system[1]. In disease models, exome sequencing and linkage analysis identified TGM6 variants that cosegregated with spinocerebellar ataxia in affected families[2]. Cellular studies further showed that different TGM6 mutations can reduce TG6 activity or induce unfolded protein response, supporting variant-specific mechanisms in SCA35[3]. Compared with related transglutaminase isoforms, TG6 is emphasized as the neuronal-specific isoform, whereas TG2 is the better-characterized tissue transglutaminase[3]. In gluten ataxia, TG6 antibodies are gluten-dependent and were reported as sensitive and specific diagnostic markers, supporting TG6 as a practical target for neuroimmune biomarker research[4]. Because published evidence does not establish validated TG6-selective agonists or inhibitors, current research applications focus on genetic variants, enzymatic activity assays, CNS expression, and TG6 autoantibody detection[1][3][4].
References:
- [1]. Thomas H, et al. Transglutaminase 6: a protein associated with central nervous system development and motor function. Amino Acids. 2013 Jan;44(1):161-77. [Content Brief]
- [2]. Wang JL, et al. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain. 2010 Dec;133(Pt 12):3510-8. [Content Brief]
- [3]. Tripathy D, et al. Mutations in TGM6 induce the unfolded protein response in SCA35. Hum Mol Genet. 2017 Oct 1;26(19):3749-3762. [Content Brief]
- [4]. Hadjivassiliou M, et al. Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology. 2013 May 7;80(19):1740-5. [Content Brief]
