endoplasmic reticulum membrane,
integral component of cytoplasmic side of endoplasmic reticulum membrane
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).