Defective PMM2 does not isomerise Man6P to Man1P

Stable Identifier
Reaction [transition]
Homo sapiens
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Phosphomannomutase 2 (PMM2) catalyses the isomerisation of mannose 6-phosphate (Man6P) to mannose 1-phosphate (Man1P) in the cytosol of cells. Man1P is a precursor in the synthesis of GDP-mannose and dolichol-phosphate-mannose, required for critical mannosyl transfer reactions in the N-glycosylation of proteins. Mutations in the PMM2 gene are one of the causes of Jaeken syndrome, a congenital disorder of glycosylation type 1a (PMM2-CDG, previously CDG-1a) (Matthijs et al. 1997). PMM2-CDG was first described in Belgian identical twin sisters, characterised by psychomotor retardation and multiple serum glycoprotein abnormalities. Serum and CSF transferrin were found to be deficient in sialic acid (Jaeken et al. 1984). The most common mutations with no detectable activity and causing a severe phenotype are R141H, D65Y, D188G, G117R and T237R (Matthijs et al. 1997, Matthijs et al. 1998, Kjaergaard et al. 1999, Vuillaumier-Barrot et al. 2000). The R141H mutation is never observed in the homozygous state. Mutations with residual activity producing a milder, less severe phenotype include F119L, C241S, C9Y, L32R and T226S (not annotated here; Vuillaumier-Barrot et al. 2000, Grunewald et al. 2001).

Literature References
PubMed ID Title Journal Year
10602363 Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli

Kjaergaard, S, Skovby, F, Schwartz, M

Eur. J. Hum. Genet. 1999
11156536 High residual activity of PMM2 in patients' fibroblasts: possible pitfall in the diagnosis of CDG-Ia (phosphomannomutase deficiency)

Schollen, E, Grünewald, S, Matthijs, G, Van Schaftingen, E, Jaeken, J

Am. J. Hum. Genet. 2001
10922383 Identification of four novel PMM2 mutations in congenital disorders of glycosylation (CDG) Ia French patients

Seta, N, Cuer, M, Grandchamp, B, Durand, G, Dupré, T, Vuillaumier-Barrot, S, Barnier, A, Hetet, G, Cormier-Daire, V, de Lonlay, P

J. Med. Genet. 2000
9140401 Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome)

Cassiman, JJ, Matthijs, G, Veiga-da-Cunha, M, Schollen, E, Jaeken, J, Van Schaftingen, E, Pardon, E

Nat Genet 1997
6543331 Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome

Eeckels, R, Corbeel, L, van der Heul, C, Eggermont, E, van Eijk, HG, Jaeken, J

Clin. Chim. Acta 1984
9497260 Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A

Schollen, E, Cassiman, JJ, Van Schaftingen, E, Matthijs, G, Jaeken, J

Am. J. Hum. Genet. 1998
Catalyst Activity

phosphomannomutase activity of PMM2 mutants [cytosol]

Normal reaction
Functional status

Loss of function of PMM2 mutants [cytosol]

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