Defective DPAGT1 does not transfer GlcNAc to DOLP

Stable Identifier
Reaction [transition]
Homo sapiens
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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
22492991 Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing

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

Hum. Mol. Genet. 2012
22742743 Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates

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

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

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

Hum Mutat 2003
Catalyst Activity

UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity of DPAGT1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of DPAGT1 mutants [endoplasmic reticulum membrane]

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