Defective ALG3 does not add mannose to the N-glycan precursor

Stable Identifier
Reaction [transition]
Homo sapiens
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Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase (ALG3) adds the sixth mannose (although the first to be derived from dolichyl-phosphate-mannose, DOLPman) to the lipid-linked oligosaccharide intermediate GlcNAc(2) Man(5) (PPDol)1 (Korner et al. 1999). Defects in ALG3 are associated with congenital disorder of glycosylation 1d (ALG3-CDG, CDG1d; MIM:601110), 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. (Sun et al. 2005). Point mutations that cause ALG3-CDG are G118D, R171Q, W71R and M157K (Korner et al. 1999, Sun et al. 2005, Kranz et al. 2007).
Literature References
PubMed ID Title Journal Year
10581255 Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase

K├Ârner, C, Lehle, L, von Figura, K, Marquardt, T, Stephani, U, Knauer, R

EMBO J. 1999
17551933 CDG-Id in two siblings with partially different phenotypes

Krasnewich, D, Freeze, HH, Sun, L, Casey, JR, Eklund, EA, Kranz, C

Am. J. Med. Genet. A 2007
15840742 Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia

Cohen, J, Chung, WK, Freeze, HH, Wang, C, Eklund, EA, Sun, L

J Clin Endocrinol Metab 2005
Catalyst Activity

alpha-1,3-mannosyltransferase activity of ALG3 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of ALG3 mutants [endoplasmic reticulum membrane]

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