Defective ALG1 does not transfer the first Man to the N-glycan precursor

Stable Identifier
Reaction [transition]
Homo sapiens
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Chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) normally tranfers a mannose moiety to the lipid-linked oligosaccharide (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins. Defects in ALG1 can cause congenital disorder of glycosylation 1k (ALG1-CDG, previously known as CDG1k; MIM:608540), a multisystem disorder characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Compared to other CDGs, ALG1-CDG has a very severe phenotype, which can result in an early death. Mutations in ALG1 causing ALG1-CDG include S258L, G342P, S150R, M377V, G145D, C396* and R276W (Schwarz et al. 2004, Kranz et al. 2004, Grubenmann et al. 2004, Dupre et al. 2010).
Literature References
PubMed ID Title Journal Year
14709599 Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik

Hennet, T, Mayatepek, E, Frank, CG, Matthijs, G, Grubenmann, CE, Schollen, E, Berger, EG, Hülsmeier, AJ, Aebi, M

Hum Mol Genet 2004
14973782 Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I

Denecke, J, Gudowius, S, Sohlbach, K, Rossi, R, Meinhardt, F, Lehle, L, Jeske, S, Marquardt, T, Kranz, C

Am J Hum Genet 2004
20679665 Guanosine diphosphate-mannose:GlcNAc2-PP-dolichol mannosyltransferase deficiency (congenital disorders of glycosylation type Ik): five new patients and seven novel mutations

Seta, N, Afenjar, A, Barnérias, C, Napuri, S, Dupré, T, Moore, SE, Le Bizec, C, Feillet, F, de Lonlay, P, Chantret, I, Yayé, HS, Altuzarra, C, Burglen, L, Vuillaumier-Barrot, S

J. Med. Genet. 2010
14973778 Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik

Lübbehusen, J, Körner, C, Dorland, B, Lehle, L, von Figura, K, Thiel, C, Schwarz, M, de Koning, T

Am J Hum Genet 2004
Catalyst Activity

chitobiosyldiphosphodolichol beta-mannosyltransferase activity of ALG1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of ALG1 mutants [endoplasmic reticulum membrane]

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