GFUS Gene: GDP-L-fucose synthase – Function, Mutations, and Disease Associations

The GFUS gene encodes GDP-L-fucose synthase, a NADP-dependent epimerase/reductase that catalyzes the conversion of GDP-4-keto-6-deoxy-D-mannose to GDP-L-fucose. This is the final step in the de novo pathway for GDP-L-fucose biosynthesis. GDP-L-fucose is the essential donor substrate for fucosyltransferases, which add fucose residues to glycoproteins and glycolipids, influencing cell adhesion, immune response, and development. Mutations in GFUS cause congenital disorder of glycosylation type IIc (also known as leukocyte adhesion deficiency type II), characterized by severe infections, growth delay, and neurological deficits.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• De novo GDP-L-fucose biosynthesis (Reactome: R-HSA-6783589)

• Fucosylation of glycoproteins (Reactome: R-HSA-6783588)

• Metabolism of carbohydrates (Reactome: R-HSA-71387)

GDP-L-fucose synthase (UniProt Q13630) is a 321-amino acid protein that functions as a homodimer. It belongs to the short-chain dehydrogenase/reductase (SDR) family and uses NADP(H) as a cofactor. The enzyme catalyzes the epimerization and reduction of GDP-4-keto-6-deoxy-D-mannose to GDP-L-fucose. This protein is localized in the cytosol and is essential for the production of fucose donors used by fucosyltransferases in the Golgi. Deficiency leads to global fucosylation defects.