Phosphoglucomutase 3 (PGM3)

Phosphoglucomutase 3 (PGM3) is an enzyme critical for the hexosamine biosynthesis pathway, catalyzing the reversible conversion of N-acetylglucosamine-6-phosphate to N-acetylglucosamine-1-phosphate, a necessary step for generating UDP-N-acetylglucosamine (UDP-GlcNAc)[1][3][7][9]. UDP-GlcNAc is a key sugar donor for N- and O-glycosylation, which modifies a vast range of proteins and lipids critical for diverse cellular processes. PGM3 deficiency results in impaired glycosylation, leading to severe combined immunodeficiencies, increased susceptibility to infections (notably due to reduced CD4+ T cell numbers and function), skeletal, and neurological abnormalities. Mutations in PGM3 cause Immunodeficiency 23 (IMD23) and are associated with a spectrum of congenital disorders of glycosylation and Hyper IgE syndrome-like phenotypes[5][7][9]. PGM3 has emerged as an important molecular node in immune regulation and metabolism but remains an experimental or discovery-stage therapeutic target, with no established or clinically approved drugs.

Other names

AGM1PAGMIMD23Acetylglucosamine phosphomutasePhosphoacetylglucosamine mutaseN-acetylglucosamine-phosphate mutase

Experimental inhibition: Reduces UDP-GlcNAc synthesis, impairs glycan branching and O-GlcNAcylation, alters T cell metabolism and proliferation. No therapeutic drugs/mechanisms documented for clinical use.