Defective DPAGT1 does not transfer GlcNAc to DOLP

Stable Identifier
R-HSA-4549334
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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In the first committed step of N-glycan precursor (LLO) synthesis, UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) normally catalyses the transfer of N-acetylglucosamine (GlcNAc), via an alpha-1,3 linkage, to a molecule of dolichyl phosphate (DOLP). Defects in DPAGT1 can cause congenital disorder of glycosylation, type 1j (DPAGT1-CDG, previously called CDG1j; MIM:608093), a multisystem disorder characterised by under-glycosylated serum glycoproteins. Clinical features include defective nervous system development, psychomotor retardation, coagulation diorders and immunodeficiency. Mutations causing DPAGT1-CDG include Y170C, I69N and a G-A transition in intron 1 (not shown here) which results in degradation of the mutant mRNA (Wu et al. 2003, Timal et al. 2012). Defects in DPAGT1 can also cause myasthenic syndrome, congenital, with tubular aggregates, 2 (CMSTA2; MIM:614750 a syndrome that arises from impaired neuromuscular transmission and characterised by muscle weakness, especially of the limb-girdle. Mutations causing CMSTA2 include V117I, M108I, L120M, T234Hfs*116 and V264G (Belaya et al. 2012).

Literature References
PubMed ID Title Journal Year
22742743 Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates

Belaya, K, Finlayson, S, Slater, CR, Cossins, J, Liu, WW, Maxwell, S, McGowan, SJ, Maslau, S, Twigg, SR, Walls, TJ, Pascual Pascual, SI, Palace, J, Beeson, D

Am. J. Hum. Genet. 2012
22492991 Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing

Timal, S, Hoischen, A, Lehle, L, Adamowicz, M, Huijben, K, Sykut-Cegielska, J, Paprocka, J, Jamroz, E, van Spronsen, FJ, K├Ârner, C, Gilissen, C, Rodenburg, RJ, Eidhof, I, Van den Heuvel, L, Thiel, C, Wevers, RA, Morava, E, Veltman, J, Lefeber, DJ

Hum. Mol. Genet. 2012
12872255 Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij

Wu, X, Rush, JS, Karaoglu, D, Krasnewich, D, Lubinsky, MS, Waechter, CJ, Gilmore, R, Freeze, HH

Hum Mutat 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity of DPAGT1 mutants [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
congenital disorder of glycosylation type I 0050570
Authored
Reviewed
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