Functional and structural analysis of double and triple mutants reveals the contribution of protein instability to clinical manifestations of G6PD variants.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. Over 200 point mutations have been identified in g6pd and the molecular mechanisms underlying the severity of G6PD variants differ. We report the detailed functional and structural characterization of 11 recombinant human G6PD variants: G6PD Asahi, G6PD A, G6PD Guadalajara, G6PD Acrokorinthos, G6PD Ananindeua, G6PD A, G6PD Sierra Leone, G6PD A, G6PD A, G6PD Mount Sinai and G6PD No name.

A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown.