Phosphoglucomutase 1 (PGM1)

Phosphoglucomutase 1 is an evolutionarily conserved cytosolic enzyme of 562 amino acids, predominant in most human tissues except red blood cells, where PGM2 prevails. It catalyzes the reversible transfer of a phosphate group between glucose's 1 and 6 positions, which is essential for normal carbohydrate handling. Mutations in the *PGM1* gene cause rare but clinically significant metabolic diseases, including congenital disorders of glycosylation and glycogen storage disease type XIV, typically resulting in defects in energy metabolism and glycoprotein synthesis. The enzyme structure features four domains with a central active site containing a key phosphoserine residue, a metal-binding loop (usually interacting with magnesium or other divalent cations), a sugar-binding loop, and a phosphate-binding site—all of which are highly conserved across species. PGM1 is also used as a genetic and biochemical marker for isozyme polymorphism and, through its role in core metabolic processes, could become a future therapeutic target for inherited metabolic disorders.

Other names

PGM1CDG1TGlycogen storage disease type XIV protein (formerly)

No current drugs approved; potential future drugs may act as enzyme activators, stabilizers, or substrate analogs to restore PGM1 function or compensate for metabolic block