UDP-N-acetylglucosamine transferase subunit ALG14 (ALG14)

UDP-N-acetylglucosamine transferase subunit ALG14 (ALG14) is an endoplasmic reticulum membrane-bound protein, acting as a key subunit of the UDP-N-acetylglucosamine (UDP-GlcNAc) transferase complex, along with ALG13. This complex catalyzes the addition of the second N-acetylglucosamine (GlcNAc) to the growing lipid-linked oligosaccharide precursor during the initial steps of protein N-linked glycosylation. ALG14 functions as a protein-membrane adapter, recruiting ALG13, and allowing the enzymatic transfer of GlcNAc. Defects in ALG14 impair N-glycosylation, leading to under-glycosylated proteins. Mutations cause congenital disorders such as ALG14-CDG (a type of congenital disorder of glycosylation) and congenital myasthenic syndrome (CMS), which manifest as neuromuscular and multi-systemic symptoms. ALG14 is not currently a direct pharmacologic target but is symptomatic in disease contexts, with some CMS patients responding to acetylcholinesterase inhibitors such as pyridostigmine. Given ALG14’s essential role in glycoprotein biosynthesis, it is not considered a typical drug target due to the toxicity risk associated with its inhibition[1][3][4][7].

Other names

ALG14UDP-N-acetylglucosaminyltransferase subunitAsparagine-linked glycosylation 14 homologCMS15IDDEBFMEPCAUDP-N-acetylglucosamine transferase subunit ALG14 homologMGC19780

Genetic deficiency treated symptomatically by acetylcholinesterase inhibitors (such as pyridostigmine), which increase acetylcholine availability at the neuromuscular junction in CMS