Defective ALG9 does not add the last mannose to the N-glycan precursor

Stable Identifier
R-HSA-9035514
Type
Reaction [transition]
Species
Homo sapiens
Compartment
endoplasmic reticulum membrane, integral component of lumenal side of endoplasmic reticulum membrane
ReviewStatus
5/5
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Defective ALG9 does not add the last mannose to the N-glycan precursor
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Alpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. Defects in ALG9 are associated with congenital disorder of glycosylation 1l (ALG9-CDG, CDG1l; MIM:608776), a multisystem disorder caused by a defect in glycoprotein biosynthesis and 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 (Frank et al. 2004, Weinstein et al. 2005). The LLO profile showed accumulation of (GlcNAc)2 (Man)6 (PP-Dol)1 and (GlcNAc)2 (Man)8 (PP-Dol)1 fragments, suggesting a defect in ALG9 and correlating with the normal function of ALG9 in adding the 7th and 9th mannose moieties (Frank et al. 2004). Point mutations that can cause ALG9-CDG are E523K and Y286C (Frank et al. 2004, Weinstein et al. 2005).
Literature References
PubMed ID Title Journal Year
15148656 Identification and functional analysis of a defect in the human ALG9 gene: definition of congenital disorder of glycosylation type IL

Hennet, T, Eyaid, W, Frank, CG, Grubenmann, CE, Berger, EG, Aebi, M

Am J Hum Genet 2004
15945070 CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic features

Hennet, T, Clarke, JT, Frank, CG, Seargeant, L, Matthijs, G, Neupert, C, Grubenmann, CE, Weinstein, M, Poplawski, N, Schollen, E, Griffiths, A, Aebi, M

Am J Med Genet A 2005
Participants
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Catalyst Activity

alpha-1,2-mannosyltransferase activity of ALG9 mutants [endoplasmic reticulum membrane]

Physical Entity
ALG9 mutants [endoplasmic reticulum membrane] (Homo sapiens)
Activity
alpha-1,2-mannosyltransferase activity (GO:0000026)
Normal reaction
ALG9 transfers Man to N-glycan precursor (GlcNAc)2 (Man)8 (PP-Dol)1 (Homo sapiens)
Functional status

Loss of function of ALG9 mutants [endoplasmic reticulum membrane]

Normal Entity
Disease Entity
Status
Disease
Authored
Jassal, B  (2013-10-21)
Reviewed
Belaya, K  (2014-10-31)
Created
Jassal, B  (2013-10-21)
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