GMDS Gene - GDP-Mannose 4,6-Dehydratase | Function, Mutations & Disease

The GMDS gene encodes GDP-mannose 4,6-dehydratase, a key enzyme in the de novo synthesis of GDP-fucose, which is essential for fucosylation of glycoproteins and glycolipids. Fucosylation plays critical roles in cell adhesion, immune response, and development. Mutations in GMDS cause congenital disorder of glycosylation type IIc (CDG IIc, also known as leukocyte adhesion deficiency type II), and altered expression is associated with cancer progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GDP-fucose biosynthesis (de novo pathway)

• Fucosylation of glycoproteins and glycolipids

• Metabolism of carbohydrates

GDP-mannose 4,6-dehydratase (GMDS) is a 42 kDa cytosolic enzyme that catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first committed step in the de novo synthesis of GDP-fucose. The enzyme belongs to the short-chain dehydrogenase/reductase (SDR) family. GDP-fucose is the donor substrate for fucosyltransferases, which add fucose residues to glycans. Proper fucosylation is critical for selectin-mediated leukocyte adhesion, immune surveillance, and cell signaling. Loss of GMDS function leads to CDG IIc, while reduced expression in cancers correlates with metastatic potential.