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Gene Review

GNMT  -  glycine N-methyltransferase

Homo sapiens

Synonyms: Glycine N-methyltransferase
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Disease relevance of GNMT

  • Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer [1].
  • Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer [1].
  • Furthermore, the dose-dependent inhibition of BaP-7,8-diol 9,10-epoxide-DNA adduct formation by GNMT was observed in HepG2 cells infected with different multiplicities of infection of recombinant adenoviruses carrying GNMT cDNA [2].
  • GNMT cDNA, which was cloned into a pMAMneo vector containing the Rous sarcoma virus promoter and the neomycin resistance gene, was stably transfected into D422 Chinese hamster ovary (CHO) cells [3].
  • Three different preparations of rat GNMT were analyzed: (1) purified from liver by standard methods of protein purification, (2) prepared from isolated hepatocytes and from liver tissue by immunoprecipitation, and (3) recombinant protein expressed in Escherichia coli [4].
  • Our findings suggest that GNMT is a tumor susceptibility gene for prostate cancer [5].

High impact information on GNMT

  • The higher AdoMet levels in neurologically affected patients may result from inhibition of glycine N-methyltransferase by those patients' higher folate levels [6].
  • Ethanol feeding alone reduced the activities of methionine synthase (MS) and MATIII and increased the activity of GNMT [7].
  • According to an aryl hydrocarbon hydroxylase enzyme activity assay, GNMT inhibited BaP-induced cytochrome P450 1A1 enzyme activity [2].
  • Based on the identification of GNMT as a 4 S polyaromatic hydrocarbon-binding protein, we used liver cancer cell lines that expressed GNMT either transiently or stably in cDNA transfections to analyze the role of GNMT in the benzo(a)pyrene (BaP) detoxification pathway [2].
  • Results from an indirect immunofluorescent antibody assay showed that GNMT was expressed in cell cytoplasm before BaP treatment and translocated to cell nuclei after BaP treatment [2].

Biological context of GNMT


Anatomical context of GNMT

  • Immunohistochemical staining with rabbit anti-recombinant GNMT serum showed that GNMT protein almost completely disappeared in liver-cancer cells, while it was abundant in the non-tumorous liver cells [9].
  • Northern blot analysis of 16 tissues from different human organs showed that GNMT was expressed only in liver, pancreas, and prostate [10].
  • Western blot analysis indicated the expression of significant levels of the 4 S protein in the stably transfected CHO cells (CHO-GNMT) [3].
  • Polyclonal antibodies to GNMT immunoprecipitated PAH-binding activity from rat liver cytosol [11].

Associations of GNMT with chemical compounds


Other interactions of GNMT


Analytical, diagnostic and therapeutic context of GNMT


  1. Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Tseng, T.L., Shih, Y.P., Huang, Y.C., Wang, C.K., Chen, P.H., Chang, J.G., Yeh, K.T., Chen, Y.M., Buetow, K.H. Cancer Res. (2003) [Pubmed]
  2. Glycine N-methyltransferase tumor susceptibility gene in the benzo(a)pyrene-detoxification pathway. Chen, S.Y., Lin, J.R., Darbha, R., Lin, P., Liu, T.Y., Chen, Y.M. Cancer Res. (2004) [Pubmed]
  3. Glycine N-methyltransferase is an example of functional diversity. Role as a polycyclic aromatic hydrocarbon-binding receptor. Bhat, R., Bresnick, E. J. Biol. Chem. (1997) [Pubmed]
  4. Identification of phosphorylation sites in glycine N-methyltransferase from rat liver. Luka, Z., Ham, A.J., Norris, J.L., Yeo, E.J., Yermalitsky, V., Glenn, B., Caprioli, R.M., Liebler, D.C., Wagner, C. Protein Sci. (2006) [Pubmed]
  5. Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer. Huang, Y.C., Lee, C.M., Chen, M., Chung, M.Y., Chang, Y.H., Huang, W.J., Ho, D.M., Pan, C.C., Wu, T.T., Yang, S., Lin, M.W., Hsieh, J.T., Chen, Y.M. Clin. Cancer Res. (2007) [Pubmed]
  6. Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism. Carmel, R., Melnyk, S., James, S.J. Blood (2003) [Pubmed]
  7. Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Villanueva, J.A., Halsted, C.H. Hepatology (2004) [Pubmed]
  8. The glycine N-methyltransferase (GNMT) 1289 C->T variant influences plasma total homocysteine concentrations in young women after restricting folate intake. Beagle, B., Yang, T.L., Hung, J., Cogger, E.A., Moriarty, D.J., Caudill, M.A. J. Nutr. (2005) [Pubmed]
  9. Characterization of glycine-N-methyltransferase-gene expression in human hepatocellular carcinoma. Chen, Y.M., Shiu, J.Y., Tzeng, S.J., Shih, L.S., Chen, Y.J., Lui, W.Y., Chen, P.H. Int. J. Cancer (1998) [Pubmed]
  10. Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene. Chen, Y.M., Chen, L.Y., Wong, F.H., Lee, C.M., Chang, T.J., Yang-Feng, T.L. Genomics (2000) [Pubmed]
  11. Rat liver cytosolic 4 S polycyclic aromatic hydrocarbon-binding protein is glycine N-methyltransferase. Raha, A., Wagner, C., MacDonald, R.G., Bresnick, E. J. Biol. Chem. (1994) [Pubmed]
  12. Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Luka, Z., Cerone, R., Phillips, J.A., Mudd, H.S., Wagner, C. Hum. Genet. (2002) [Pubmed]
  13. Glycine N -methyltransferase deficiency: a new patient with a novel mutation. Augoustides-Savvopoulou, P., Luka, Z., Karyda, S., Stabler, S.P., Allen, R.H., Patsiaoura, K., Wagner, C., Mudd, S.H. J. Inherit. Metab. Dis. (2003) [Pubmed]
  14. SNP detection and genetic mapping of porcine genes encoding enzymes in hepatic metabolic pathways and evaluation of linkage with carcass traits. Ponsuksili, S., Chomdej, S., Murani, E., Bläser, U., Schreinemachers, H.J., Schellander, K., Wimmers, K. Anim. Genet. (2005) [Pubmed]
  15. Human glycine N-methyltransferase is unfolded by urea through a compact monomer state. Luka, Z., Wagner, C. Arch. Biochem. Biophys. (2003) [Pubmed]
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