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Gene Review

GPM6A  -  glycoprotein M6A

Homo sapiens

Synonyms: GPM6, M6A, M6a, Neuronal membrane glycoprotein M6-a
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Disease relevance of GPM6A

  • We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria [1].
  • Patients with this type of leukemia traditionally have been treated with a standard myeloid protocol, with a wide variation in prognosis between M6a, which has a similar prognosis to acute myelogenous leukemias, and M6b, with an extremely poor outcome despite aggressive therapy [2].
  • RESULTS: Fifty-three patients met the criteria of M6a subtype of the WHO classification, and 2 were classified as having pure erythremia (M6b); 7 cases could not be classified according to the WHO criteria [3].

High impact information on GPM6A

  • The genes for membrane glycoprotein (M6a) and chloride channel 3 (CLCN3) were analyzed by direct sequencing for mutations [4].
  • To date, three different gene products, DMalpha/DM-20/PLP, DMbeta/M6a, and DMgamma/M6b, have been isolated from certain primitive fish species, mouse, and human central nervous system (CNS) [5].
  • M6a appeared in post-mitotic neurons of the brain and spinal cord as early as E10, and later in the hippocampus, cerebral cortex, and the granule cells of the cerebellum [6].
  • These results support the idea that M6a implicates in neuronal differentiation as a novel Ca(2+) channel gated selectively by phosphorylation with PKC in the downstream of NGF signaling pathway [7].
  • Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia [8].

Biological context of GPM6A


Anatomical context of GPM6A


Associations of GPM6A with chemical compounds

  • Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to 4q33-->q34 [9].
  • The minor metabolites were identified, by LC-MS/MS comparison with synthetic standards or by NMR, as acyl glucuronide (M1), sulfoxide (M2), 25-hydroxy (a phenol, M3), 21-hydroxy (diastereomers of a benzylic alcohol, M5a and M5b), and 36-hydroxy (diastereomers of a methyl alcohol, M6a and M6b) analogs of montelukast [10].

Other interactions of GPM6A

  • Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group [1].

Analytical, diagnostic and therapeutic context of GPM6A


  1. Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis. Mazzella, F.M., Kowal-Vern, A., Shrit, M.A., Wibowo, A.L., Rector, J.T., Cotelingam, J.D., Collier, J., Mikhael, A., Cualing, H., Schumacher, H.R. Am. J. Clin. Pathol. (1998) [Pubmed]
  2. Effects of multidrug resistance gene expression in acute erythroleukemia. Mazzella, F.M., Kowal-Vern, A., Shrit, M.A., Rector, J.T., Cotelingam, J.D., Schumacher, H.R. Mod. Pathol. (2000) [Pubmed]
  3. Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Domingo-Claros, A., Larriba, I., Rozman, M., Irriguible, D., Vallespí, T., Aventin, A., Ayats, R., Millá, F., Solé, F., Florensa, L., Gallart, M., Tuset, E., Lopez, C., Woessner, S. Haematologica (2002) [Pubmed]
  4. A new locus for autosomal recessive RP (RP29) mapping to chromosome 4q32-q34 in a Pakistani family. Hameed, A., Khaliq, S., Ismail, M., Anwar, K., Mehdi, S.Q., Bessant, D., Payne, A.M., Bhattacharya, S.S. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  5. Conserved and divergent expression patterns of the proteolipid protein gene family in the amphibian central nervous system. Yoshida, M., Shan, W.S., Colman, D.R. J. Neurosci. Res. (1999) [Pubmed]
  6. Expression of members of the proteolipid protein gene family in the developing murine central nervous system. Yan, Y., Narayanan, V., Lagenaur, C. J. Comp. Neurol. (1996) [Pubmed]
  7. M6a acts as a nerve growth factor-gated Ca(2+) channel in neuronal differentiation. Mukobata, S., Hibino, T., Sugiyama, A., Urano, Y., Inatomi, A., Kanai, Y., Endo, H., Tashiro, F. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  8. Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases. Kowal-Vern, A., Mazzella, F.M., Cotelingam, J.D., Shrit, M.A., Rector, J.T., Schumacher, H.R. Am. J. Hematol. (2000) [Pubmed]
  9. Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to 4q33-->q34. Shimizu, F., Watanabe, T.K., Fujiwara, T., Takahashi, E., Nakamura, Y., Maekawa, H. Cytogenet. Cell Genet. (1996) [Pubmed]
  10. Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene1 receptor antagonist, in human plasma and bile. Balani, S.K., Xu, X., Pratha, V., Koss, M.A., Amin, R.D., Dufresne, C., Miller, R.R., Arison, B.H., Doss, G.A., Chiba, M., Freeman, A., Holland, S.D., Schwartz, J.I., Lasseter, K.C., Gertz, B.J., Isenberg, J.I., Rogers, J.D., Lin, J.H., Baillie, T.A. Drug Metab. Dispos. (1997) [Pubmed]
  11. Chromosomal mapping of the human M6 genes. Olinsky, S., Loop, B.T., DeKosky, A., Ripepi, B., Weng, W., Cummins, J., Wenger, S.L., Yan, Y., Lagenaur, C., Narayanan, V. Genomics (1996) [Pubmed]
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