Glucose 1,6-bisphosphate synthase

Glucose 1,6-bisphosphate synthase (PGM2L1) is a phosphotransferase that catalyzes the synthesis of glucose 1,6-bisphosphate using 1,3-bisphosphoglycerate as a phosphate donor and various 1-phosphate sugars—including glucose 1-phosphate, mannose 1-phosphate, ribose 1-phosphate, and deoxyribose 1-phosphate—as acceptors (UniProt: Q6PCE3). The enzyme plays a role in phosphosugar metabolism and exhibits minor phosphopentomutase and phosphoglucomutase activities of uncertain physiological significance.

PGM2L1 is implicated in neurodevelopmental function; biallelic mutations cause neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities (NEDHFS, MIM 620191), characterized by severe developmental delay, speech impairment, hypotonia, and facial dysmorphism (UniProt: Q6PCE3).

In Alzheimer's disease, PGM2L1 protein is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change −0.47; Chaparral AD proteomics). This downregulation was detected via TMT-labeled quantitative proteomics across multiple subcellular fractions, suggesting altered metabolic capacity in AD pathology.