Glucose-6-phosphate dehydrogenase (G6PD) (G6PD)

The Glucose-6-phosphate dehydrogenase (G6PD) genomic DNA locus, located at Xq28, encodes a fundamental metabolic enzyme responsible for the first step of the pentose phosphate pathway [1]. This enzyme is the sole source of NADPH in mature erythrocytes, which is vital for regenerating reduced glutathione to protect cells from oxidative stress [2]. Mutations within this genomic locus lead to G6PD deficiency, the most prevalent enzyme deficiency in humans, affecting approximately 400 million people worldwide [3]. While the enzyme is not a traditional drug target for inhibition, the locus is a critical pharmacogenomic marker; individuals with certain variants are at high risk for acute hemolytic anemia when exposed to oxidative medications like primaquine or rasburicase [4]. Consequently, the G6PD locus is a primary target for diagnostic screening and is being explored for gene-correction therapies using CRISPR/Cas9 technology to treat severe phenotypes [5]. Understanding the genetic landscape of this locus is essential for personalized medicine and safe prescribing of various antimalarial and uric acid-lowering therapies [6].

Other names

G6PDDGlucose-6-phosphate 1-dehydrogenaseMET1G6PD genomic locus

The G6PD enzyme catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconolactone, reducing NADP+ to NADPH in the process. NADPH is a crucial cofactor for glutathione reductase, which maintains reduced glutathione levels to neutralize reactive oxygen species. Drugs do not typically target G6PD for inhibition; rather, oxidative drugs increase the demand for NADPH, leading to hemolysis in G6PD-deficient cells.