MOGS Gene: Function, Mutations, and Associated Disorders (CDG-IIb)

The MOGS gene encodes the catalytic subunit of glucosidase I, an enzyme located in the endoplasmic reticulum (ER) that removes the terminal alpha-1,2-linked glucose residue from the N-linked oligosaccharide precursor Glc3Man9GlcNAc2. This trimming step is essential for proper glycoprotein folding, quality control, and subsequent trafficking. Loss-of-function mutations in MOGS cause congenital disorder of glycosylation type IIb (CDG-IIb), a severe multisystem disorder characterized by dysmorphic features, hypotonia, seizures, and developmental delay.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• N-glycan biosynthesis (Reactome R-HSA-446203)

• Asparagine N-linked glycosylation (Reactome R-HSA-446219)

• ER quality control and ERAD (Reactome R-HSA-901623)

Glucosidase I (EC 3.2.1.106) is a 92 kDa transmembrane protein localized to the ER membrane. It catalyzes the first trimming step of the N-linked glycan precursor, removing the terminal alpha-1,2-linked glucose. This action is required for proper interaction with calnexin/calreticulin chaperone cycle. The enzyme is a homodimer; each subunit contains a catalytic domain facing the ER lumen. Deficiency leads to accumulation of triglucosylated oligosaccharides and severe glycosylation defects.