Mannose-1-phosphate guanylyltransferase (GMPPB)

Mannose-1-phosphate guanylyltransferase, specifically the beta subunit (GMPPB), is a cytoplasmic enzyme essential for the biosynthesis of GDP-mannose, which serves as a critical sugar donor for various glycosylation reactions (UniProt, Q9Y5P6). It catalyzes the conversion of mannose-1-phosphate and GTP into GDP-mannose and diphosphate, a step that is vital for the O-mannosylation of alpha-dystroglycan, a protein necessary for muscle membrane stability and brain development (PubMed, 23913003). Mutations in the GMPPB gene lead to a spectrum of clinical disorders known as dystroglycanopathies, ranging from severe congenital muscular dystrophy with brain and eye involvement to milder adult-onset limb-girdle muscular dystrophy (OMIM, 615320). While there are currently no approved small-molecule inhibitors for this enzyme, it is a primary focus for therapeutic research involving gene replacement and metabolic supplementation strategies aimed at restoring glycosylation levels (PubMed, 30103144). Monitoring the glycosylation patterns of alpha-dystroglycan in muscle biopsies remains a key diagnostic and efficacy biomarker for assessing the functional impact of this target (PubMed, 26338921).

Other names

GDP-mannose pyrophosphorylase BGMPPMannose-1-phosphate guanylyltransferase betaGDP-Man PP

Catalysis of GDP-mannose synthesis to provide substrates for mannosyltransferases in the endoplasmic reticulum and Golgi apparatus