Alt. symbols: G6PD1

Approved name: glucose-6-phosphate dehydrogenase
Alt. names: glucose6phosphate 1dehydrogenase

Location: Xq28: 154517825 - 154547572 (-)
Gene type: protein_coding, 24 transcripts.

Scores: LoFtool: 0.016900 | pLI: 0.96639145 | LOEUF: 0.318

HGNC: 4057

NCBI: 2539, RefSeq: NG_009015.2

Ensembl: ENSG00000160211.20

LRG_148 | Status: public

OMIM: 305900

Expression | ProteinAtlas

G6PD encodes the glucose-6-phosphate dehydrogenase enzyme, which plays a key role in the production of ribose 5-phosphate and catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which is the only NADPH-generation process in mature red cells. Thus, the main function of this enzyme is to provide reducing power (NADPH) for mature red cells, which lack the citric acid cycle, and to generate pentose phosphates for fatty acid and nucleic acid synthesis.

X-linked G6PD deficiency is the most common genetic cause of chronic and drug-, food-, or infection-induced hemolytic anemia [MIM:300908], affecting an estimated 400 million individuals worldwide (PMID: 8579052). Over 400 different genetic variants of G6PD deficiency have been reported, and the precise mutation is known for at leas 217 of these (PMID: 27941691). Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can also be life-threatening, especially in ne onates with hyperbilirubinemia that may be at risk for kernicterus. Affected individuals remain at risk for episodes of acute hemolytic anemia triggered by infection, an exogenous agent (i.e. primaquine or fava beans) or other forms of oxidative stress to erythrocytes, manifesting as fatigue, back pain, anemia, and jaundice, as well as increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria is endemic provided evidence that G6PD deficiency confers resistance against malaria {Resistance to malaria due to G6PD deficiency} [MIM:611162]. All G6PD mutations known, except G6PD A (N126D), are associated with more or less severe enzyme deficiency but never with complete loss of activity, which would be lethal (PMID: 27040960). Variants of G6PD deficiency have been classified by the WHO according to the level of enzyme activity (last revision in 1989): Class 1 - severe enzyme deficiency associated with chronic nonspherocytic hemolytic anemia (CNSHA); Class 2 - severe enzyme deficiency (less than 10% residual activity) associated with acute hemolytic anemia; Class 3 – mild to moderate enzyme deficiency (10-60% residual activity); Class 4 - very mild or no enzyme deficiency (60-150% activity); and Class 5 - increased enzyme activity (PMID: 2633878). More severe mutations associated with CNSHA tend to cluster near the C-terminus of the enzyme, while clinically milder mutations tend to cluster towards the N-terminal end. Additionally, because G6PD deficiency may lead to a shortage of NADPH, severe G6PD deficiency may also result in secondarily defective NADPH oxidase activity and induce CGD-like symptoms along with abnormal DHR or NBT testing (PMID: 10556177, 12130518, 27458052, 34175765). Some G6PD mutations that have been associated with CGD-like disease are c.180_182delTCT (p.Leu61del), c.477G>C (p.Met159Ile), c.496C>T (p.Arg166Cys), c.514C>T (p.Pro172Ser), c.563C>T (p.Ser188Phe), c.844G>C (p.Asp282His), and c.1361G>C (p.Arg454Pro) (PMID: 34175765). [Load More]