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Gene Review

MPI  -  mannose phosphate isomerase

Homo sapiens

Synonyms: CDG1B, Mannose-6-phosphate isomerase, PMI, PMI1, Phosphohexomutase, ...
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Disease relevance of MPI


Psychiatry related information on MPI

  • This study provides psychometric data to support the use of the PMI and information about factors associated with use of active and passive coping strategies in pain sufferers [6].
  • Use of the PMI for career counseling/decisions in nursing is not recommended, however, its use as an organizational development tool is endorsed [7].

High impact information on MPI

  • An antiplatelet monoclonal antibody, PMI-1, reacts with glycoproteins (GP) GPIIb, free GPIIb, and the GPIIb-IIIa complex [8].
  • The PMI-1 epitope was found to be contained within a 9-kDa staphylococcal V8 protease fragment of GPIIb, and such a fragment was predicted within the putative heavy-chain sequence [9].
  • A cDNA clone that directs the synthesis of a fusion protein reactive with the PMI-1 antibody was isolated from a phage lambda gt11 expression library constructed with mRNA from an erythroleukemia (HEL) cell line [9].
  • The oxygen consumption obtained for PMIP compared with available cumulative data on normal subjects is significantly variable, suggesting the need for caution when prescribing exercise for the PMIP based on energy costs of standard exercise measurements in normals [5].
  • A relationship between the absence and presence of the heteropolymeric molecule, mannosephosphate isomerase (MPI), and pyruvate kinase (PK-3), assigned to chromosome 15, was established [10].

Chemical compound and disease context of MPI


Biological context of MPI

  • Furthermore, mutational analysis of the MPI gene revealed two missense mutations, 419 T --> C (I140T) and 636 G --> A (R219Q), a single base substitution in intron 5, 670 + 9G --> A, as well as a polymorphism 1131A --> C (V377V) in both sibs [16].
  • Phosphomannose isomerase catalyses the interconversion of fructose-6-P and mannose-6-P and has a critical role in the supply of D-mannose derivatives required for many eukaryotic glycosylation reactions [17].
  • Based on amino acid sequence identity we propose a classification system for enzymes with phosphomannose-isomerase activity [17].
  • Confirmation of the synteny of the human genes for mannose phosphate isomerase and pyruvate kinase and of their assignment to chromosome 15 [18].
  • Electrophoretic patterns in F1 hybrid heterozygotes confirmed the monomeric structures of MPI and the esterase and the tetrametric structure of LDH in these fishes [19].

Anatomical context of MPI


Associations of MPI with chemical compounds

  • These results suggest that the clinical manifestations of PMI deficiency, although serious in childhood, can improve with age, even without mannose therapy, and allow for a normal adult life [16].
  • In contrast to some other bacterial GDP-mannose pyrophosphorylases, the mycobacterial enzyme was not multifunctional and did not have phosphomannose isomerase or phosphoglucose isomerase activity [24].
  • Five enzymes, malate dehydrogenase, lactate dehydrogenase, mannose-phosphate isomerase, glucose-phosphate isomerase and phosphoglucomutase from seven putative species of Ostertagiinae were compared using starch-gel electrophoresis [25].
  • A selection system based on the phosphomannose-isomerase gene (pmi) as a selectable marker and mannose as the selective agent was evaluated for the transformation of apple (Malus domestica Borkh.). Mannose is an unusable carbon source for many plant species [2].
  • Furthermore, the binding of PMI-1 and anti-LIBS1 increased in response to GRGDSP, confirming a defect in agonist-mediated fibrinogen receptor activation rather than in fibrinogen binding or events distal to binding [26].

Physical interactions of MPI

  • The peptide-antibody complex has an approximate Kd of 1.2 microM, which compares to a Kd of 0.95 microM for PMI-1 binding to GPIIb [9].

Other interactions of MPI

  • New mutations were identified in MPI (Y129C) and ALG6 (G227E) [27].
  • We therefore compared the frequency of this variant in 301 controls and in 101 CDG patients who carry known mutations in other genes involved in CDG, i.e. PMM2 (CDG-Ia; 91 patients) and MPI (CDG-Ib; 10 patients) [28].
  • An abnormal serum transferrin isoelectric focusing (IEF) pattern and a reduced PMI activity confirmed the diagnosis of CDG-Ib [16].
  • Three patients, including the one with the normal transferrin profile, did not have a deficiency of phosphomannomutase or phosphomannose isomerase (CDGS 1b) [29].
  • The following syntenic groups were observed but could not be localized: GUK1-FH and MPI-PKM2 [30].

Analytical, diagnostic and therapeutic context of MPI

  • The successful treatment of CDG Ib patients with oral mannose emphasises the paramount importance of early diagnosis of PMI deficiency [31].
  • However, the brief screening version of MPI showed acceptable validity and reliability, except for rather low alpha values in sections 3 and 4 [32].
  • CONCLUSION: Attenuation maps from CCS allow accurate AC of SPECT MPI images [33].
  • The relationship between RV MPI and the end point of all-cause mortality, transplantation, or ventricular assist device placement was evaluated [34].
  • METHODS: The MPI was measured in 63 consecutive patients (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex-matched controls [4].


  1. Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy. Niehues, R., Hasilik, M., Alton, G., Körner, C., Schiebe-Sukumar, M., Koch, H.G., Zimmer, K.P., Wu, R., Harms, E., Reiter, K., von Figura, K., Freeze, H.H., Harms, H.K., Marquardt, T. J. Clin. Invest. (1998) [Pubmed]
  2. The use of the phosphomannose-isomerase/mannose selection system to recover transgenic apple plants. Degenhardt, J., Poppe, A., Montag, J., Szankowski, I. Plant Cell Rep. (2006) [Pubmed]
  3. Role of exercise tolerance test (ETT) and gated single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) in predicting severity of ischemia in patients with chest pain. Banerjee, S.K., Haque, K.M., Sharma, A.K., Ahmed, C.M., Iqbal, A.T., Nisa, L. Bangladesh Medical Research Council bulletin. (2005) [Pubmed]
  4. The Myocardial Performance Index detects chronic cardiac allograft dysfunction sooner than other methods. Frea, S., Morello, M., Bobbio, M., Saviolo, R., Mangiardi, L., Trevi, G.P. The Journal of cardiovascular surgery. (2006) [Pubmed]
  5. Oxygen consumption and hemodynamic response of exercises used in training of patients with recent myocardial infarction. Fletcher, G.F., Cantwell, J.D., Watt, E.W. Circulation (1979) [Pubmed]
  6. Coping with neck and low back pain in the general population. Mercado, A.C., Carroll, L.J., Cassidy, J.D., Côté, P. Health psychology : official journal of the Division of Health Psychology, American Psychological Association. (2000) [Pubmed]
  7. Measuring managerial motivation: the Power Management Inventory. Henderson, M.C. Journal of nursing measurement. (1993) [Pubmed]
  8. Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia. Ginsberg, M.H., Lightsey, A., Kunicki, T.J., Kaufmann, A., Marguerie, G., Plow, E.F. J. Clin. Invest. (1986) [Pubmed]
  9. Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb involved in adhesive function. Loftus, J.C., Plow, E.F., Frelinger, A.L., D'Souza, S.E., Dixon, D., Lacy, J., Sorge, J., Ginsberg, M.H. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  10. Characterization of beta-D-N-acetylhexosaminidase isoenzymes in man-Chinese hamster somatic cell hybrids. Hoeksema, H.L., Reuser, A.J., Hoogeveen, A., Westerveld, A., Braidman, I., Robinson, D. Am. J. Hum. Genet. (1977) [Pubmed]
  11. Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation. Jaeken, J., Matthijs, G., Saudubray, J.M., Dionisi-Vici, C., Bertini, E., de Lonlay, P., Henri, H., Carchon, H., Schollen, E., Van Schaftingen, E. Am. J. Hum. Genet. (1998) [Pubmed]
  12. Selenomethionine labelling of phosphomannose isomerase changes its kinetic properties. Bernard, A.R., Wells, T.N., Cleasby, A., Borlat, F., Payton, M.A., Proudfoot, A.E. Eur. J. Biochem. (1995) [Pubmed]
  13. Therapy of symptomatic pericarditis after myocardial infarction: retrospective and prospective studies of aspirin, indomethacin, prednisone, and spontaneous resolution. Berman, J., Haffajee, C.I., Alpert, J.S. Am. Heart J. (1981) [Pubmed]
  14. The Burkholderia cepacia bceA gene encodes a protein with phosphomannose isomerase and GDP-d-mannose pyrophosphorylase activities. Sousa, S.A., Moreira, L.M., Wopperer, J., Eberl, L., S??-Correia, I., Leit??o, J.H. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  15. Changes in serum biochemical responses during cardiac rehabilitation. Brodie, D.A., Liu, X., Jackson, M. Medicine and science in sports and exercise. (2003) [Pubmed]
  16. Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. Westphal, V., Kjaergaard, S., Davis, J.A., Peterson, S.M., Skovby, F., Freeze, H.H. Mol. Genet. Metab. (2001) [Pubmed]
  17. Purification, cDNA cloning and heterologous expression of human phosphomannose isomerase. Proudfoot, A.E., Turcatti, G., Wells, T.N., Payton, M.A., Smith, D.J. Eur. J. Biochem. (1994) [Pubmed]
  18. Confirmation of the synteny of the human genes for mannose phosphate isomerase and pyruvate kinase and of their assignment to chromosome 15. Chern, C.J., Croce, C.M. Cytogenet. Cell Genet. (1975) [Pubmed]
  19. Polymorphisms, linkage and mapping of four enzyme loci in the fish genus Xiphophorus (Poeciliidae). Morizot, D.C., Siciliano, M.J. Genetics (1979) [Pubmed]
  20. Establishment and characterization of a new continuous cell line from Lutzomyia longipalpis (Diptera: psychodidae) and its susceptibility to infections with arboviruses and Leishmania chagasi. Rey, G.J., Ferro, C., Bello, F.J. Mem. Inst. Oswaldo Cruz (2000) [Pubmed]
  21. Synteny relationship between the human loci for hexosaminidase-a, mannose phosphate isomerase, and pyruvate kinase-3 studied in man-Chinese hamster somatic cell hybrids. Westerfeld, A., van Someren, H., Beyersbergen van Henegouwen, H.M., Oosterbaan, R.A. Cytogenet. Cell Genet. (1975) [Pubmed]
  22. Inhibitory effect of mannose on erythrocyte defense against oxidants. Lachant, N.A., Zerez, C.R. Biochim. Biophys. Acta (1988) [Pubmed]
  23. Agglutination of isolated platelet membranes. Gawaz, M., Ott, I., Reininger, A.J., Heinzmann, U., Neumann, F.J. Arterioscler. Thromb. Vasc. Biol. (1996) [Pubmed]
  24. Purification and properties of mycobacterial GDP-mannose pyrophosphorylase. Ning, B., Elbein, A.D. Arch. Biochem. Biophys. (1999) [Pubmed]
  25. Species and morphs in the Ostertagiinae: an allozyme study of seven species. Gasnier, N., Cabaret, J., Suarez, V. Int. J. Parasitol. (1993) [Pubmed]
  26. Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies. Ginsberg, M.H., Frelinger, A.L., Lam, S.C., Forsyth, J., McMillan, R., Plow, E.F., Shattil, S.J. Blood (1990) [Pubmed]
  27. DHPLC analysis as a platform for molecular diagnosis of congenital disorders of glycosylation (CDG). Schollen, E., Martens, K., Geuzens, E., Matthijs, G. Eur. J. Hum. Genet. (2002) [Pubmed]
  28. A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency. Westphal, V., Kjaergaard, S., Schollen, E., Martens, K., Grunewald, S., Schwartz, M., Matthijs, G., Freeze, H.H. Hum. Mol. Genet. (2002) [Pubmed]
  29. Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1. Imtiaz, F., Worthington, V., Champion, M., Beesley, C., Charlwood, J., Clayton, P., Keir, G., Mian, N., Winchester, B. J. Inherit. Metab. Dis. (2000) [Pubmed]
  30. Comparative gene mapping of man and Cebus capucinus: a study of 23 enzymatic markers. Créau-Goldberg, N., Cochet, C., Turleau, C., de Grouchy, J. Cytogenet. Cell Genet. (1981) [Pubmed]
  31. A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases. de Lonlay, P., Seta, N., Barrot, S., Chabrol, B., Drouin, V., Gabriel, B.M., Journel, H., Kretz, M., Laurent, J., Le Merrer, M., Leroy, A., Pedespan, D., Sarda, P., Villeneuve, N., Schmitz, J., van Schaftingen, E., Matthijs, G., Jaeken, J., Korner, C., Munnich, A., Saudubray, J.M., Cormier-Daire, V. J. Med. Genet. (2001) [Pubmed]
  32. Psychometric evaluation of multidimensional pain inventory (Swedish version) in a sample of elderly people. Jakobsson, U., Horstmann, V. European journal of pain (London, England) (2006) [Pubmed]
  33. Use of coronary calcium score scans from stand-alone multislice computed tomography for attenuation correction of myocardial perfusion SPECT. Schepis, T., Gaemperli, O., Koepfli, P., R??egg, C., Burger, C., Leschka, S., Desbiolles, L., Husmann, L., Alkadhi, H., Kaufmann, P.A. Eur. J. Nucl. Med. Mol. Imaging (2007) [Pubmed]
  34. Right ventricular dysfunction and adverse outcome in patients with advanced heart failure. Field, M.E., Solomon, S.D., Lewis, E.F., Kramer, D.B., Baughman, K.L., Stevenson, L.W., Tedrow, U.B. J. Card. Fail. (2006) [Pubmed]
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