{"gene":{"symbol":"G6PD","name":"Glucose-6-Phosphate Dehydrogenase","protein":"Glucose-6-phosphate dehydrogenase","ncbi_gene_id":"2539","locus":"Xq28","summary":"G6PD encodes the enzyme that protects red blood cells from oxidative damage. Inherited deficiency is the most common enzyme defect in humans, carried by roughly 400 million people, and usually causes no symptoms until a trigger appears: fava beans, an infection, or certain medications such as rasburicase and primaquine, after which red cells can break down (hemolysis). Because the gene is on the X chromosome, deficiency affects men more often than women.","function":"G6PD runs the first step of the pentose phosphate pathway, generating NADPH, the molecule red blood cells rely on to keep their antioxidant defences (glutathione) charged. Red cells have no nucleus and cannot make new proteins, so they depend almost entirely on G6PD to survive oxidative stress. When G6PD activity is low, an oxidative challenge overwhelms the cell, hemoglobin precipitates and the red cell is destroyed: acute hemolytic anemia. The three classic trigger categories are certain drugs, fava beans (favism) and infection; deficiency can also cause prolonged newborn jaundice. Inheritance is X-linked: males have a single copy and are either deficient or not; females have two copies and can be normal, deficient, or a heterozygous carrier whose red cells are a mosaic, with activity that can range from normal to deficient, which can make enzyme testing in women harder to interpret.","category":"pharmacogene","key_variants":[{"rsid":null,"name":"G6PD B (reference)","alleles":"Wild-type allele","effect":"Normal enzyme activity; used as the reference.","frequency_note":null},{"rsid":"rs5030868","name":"G6PD Mediterranean (c.563C>T, S188F)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): G reference, A variant. G6PD is on the minus strand, so A here is the T of c.563C>T, the Mediterranean variant. G6PD is on the X chromosome: men have one copy, so counting needs the person's sex.","effect":"Deficient allele (CPIC 2023 groups it with the class II–III deficient alleles). Higher risk of favism and drug-triggered hemolysis.","frequency_note":"Frequent around the Mediterranean, Middle East and South Asia."},{"rsid":"rs1050828","name":"G6PD A- (component 1 of 2)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): C reference, T variant. G6PD is on the minus strand, so T here is the A of c.202G>A (Val68Met), the change that makes G6PD A- together with c.376A>G (rs1050829). G6PD is on the X chromosome: counting needs the person's sex.","effect":"Moderately reduced activity. Milder than Mediterranean: older red cells are most affected, so hemolysis is often self-limiting, but drug and infection triggers still matter.","frequency_note":"The common African-ancestry variant."},{"rsid":"rs1050829","name":"G6PD A- (component 2 of 2)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): T reference, C variant. G6PD is on the minus strand, so C here is the G of c.376A>G (Asn126Asp). C is carried by G6PD A, which is not deficient, and also by A- and other alleles: read it together with rs1050828. G6PD is on the X chromosome.","effect":"Together with rs1050828 defines the G6PD A- allele (moderately reduced activity).","frequency_note":"The common African-ancestry variant."},{"rsid":null,"name":"Other regional variants (Canton, Kaiping, Viangchan and others)","alleles":null,"effect":"Variable severity. Common in East and Southeast Asia and elsewhere; consumer arrays rarely cover all of them.","frequency_note":null}],"phenotypes":["Normal","Deficient","Deficient with CNSHA (chronic non-spherocytic hemolytic anemia)","Variable: one deficient and one non-deficient allele in people with more than one X chromosome; activity can range from normal to deficient, so enzyme activity must be measured","Indeterminate","Alleles grouped by historical WHO classes, from Class I (severe, with CNSHA) to Class IV (normal activity)"],"clinical_relevance":"G6PD deficiency has a CPIC guideline and appears on multiple drug labels; the practical message is avoidance. Rasburicase (used in tumor lysis syndrome) is contraindicated in G6PD deficiency because it can cause severe acute hemolysis and methemoglobinemia, and the FDA label recommends screening higher-risk patients first. The FDA labels for the antimalarials primaquine and tafenoquine require G6PD testing before use. CPIC 2023 classifies dapsone and methylene blue as high risk (avoid in deficiency), nitrofurantoin as medium risk (use with caution), and the common sulfonamides as low-to-no risk at standard doses. Deficient individuals are advised to avoid fava beans, and clinicians watch for hemolysis during infections. Clinically, what matters is the resulting enzyme activity, which is why a quantitative enzyme assay, not a single SNP, is the diagnostic standard.","consumer_array_caveat":"Consumer raw data gives partial, ancestry-dependent information. rs5030868 (Mediterranean) and rs1050828 (part of A-) are sometimes genotyped; many regional variants (Canton, Kaiping, Viangchan and others) are usually not on consumer chips, so a 'normal' raw-data readout can miss real deficiency. The gene is X-linked, so a heterozygous woman has mosaic activity that can range from normal to deficient, which genotype alone does not capture. The clinical standard is a quantitative enzyme test, not DNA; a raw-data variant is a reason to ask for an enzyme test before any at-risk medication, not a diagnosis.","drugs":[{"drug":"rasburicase","guideline":"CPIC; FDA label","level":"CPIC A","summary":"Contraindicated in G6PD deficiency: can cause severe acute hemolysis and methemoglobinemia. The FDA label recommends screening higher-risk patients before use."},{"drug":"primaquine","guideline":"CPIC","level":"CPIC A","summary":"The FDA label requires G6PD testing before use and contraindicates primaquine in severe deficiency. CPIC 2023 rates risk by dose: standard daily regimens (0.25–0.5 mg/kg for 14 days) are high risk and avoided in deficient phenotypes; the weekly 8-week regimen for P. vivax is medium risk, with close hemolysis monitoring; a single low dose (0.25 mg/kg) for P. falciparum is low-to-no risk."},{"drug":"tafenoquine","guideline":"CPIC","level":"CPIC A","summary":"The FDA label requires G6PD testing before prescribing and contraindicates tafenoquine in G6PD deficiency or unknown G6PD status. CPIC 2023 classifies it as high risk: avoid in deficient phenotypes (strong); its safety was established for G6PD activity ≥70% of normal."},{"drug":"dapsone","guideline":"CPIC","level":"CPIC A","summary":"CPIC 2023 classifies dapsone as high risk for hemolysis: avoid in G6PD-deficient phenotypes (strong recommendation); for the variable phenotype, enzyme activity must be measured."},{"drug":"nitrofurantoin","guideline":"CPIC","level":"CPIC A","summary":"CPIC 2023 (Gammal et al.) classifies nitrofurantoin as medium risk: for G6PD-deficient patients, use at standard doses with caution and close monitoring for anemia (optional); avoid in deficiency with chronic nonspherocytic hemolytic anemia (moderate); when the phenotype is variable or indeterminate, measure enzyme activity."},{"drug":"methylene blue","guideline":"CPIC","level":"CPIC A","summary":"CPIC 2023 classifies methylene blue as high risk for hemolysis: avoid in G6PD-deficient phenotypes (moderate recommendation; strong with CNSHA); for the variable phenotype, enzyme activity must be measured."},{"drug":"sulfonamides","guideline":"CPIC","level":"CPIC C","summary":"CPIC 2023 classifies sulfamethoxazole, sulfadiazine, sulfadimidine, sulfanilamide, sulfasalazine and sulfisoxazole as low-to-no risk: no reason to avoid them at standard doses in G6PD deficiency (optional, as some regulators still advise caution); with CNSHA, cautious use with monitoring."},{"drug":"pegloticase","guideline":"CPIC","level":"CPIC A","summary":"CPIC 2023 classifies pegloticase as high risk for hemolysis: avoid in G6PD-deficient phenotypes, including deficiency with CNSHA (strong recommendation); for the variable or indeterminate phenotype, enzyme activity must be measured."},{"drug":"toluidine blue","guideline":"CPIC","level":"CPIC A","summary":"CPIC 2023 classifies toluidine blue as high risk for hemolysis: avoid in G6PD-deficient phenotypes (moderate recommendation; strong with CNSHA), with strength extrapolated from methylene blue data; for the variable or indeterminate phenotype, enzyme activity must be measured."}],"sources":[{"label":"CPIC — G6PD gene page","url":"https://cpicpgx.org/gene/g6pd/"},{"label":"PharmGKB G6PD (PA28469)","url":"https://www.pharmgkb.org/gene/PA28469"},{"label":"StatPearls — G6PD deficiency","url":"https://www.ncbi.nlm.nih.gov/books/NBK470315/"},{"label":"NCBI Gene 2539","url":"https://www.ncbi.nlm.nih.gov/gene/2539"},{"label":"Gammal et al., Clin Pharmacol Ther 2023 (CPIC G6PD guideline)","url":"https://pubmed.ncbi.nlm.nih.gov/36049896/"},{"label":"Elitek (rasburicase) prescribing information, FDA/DailyMed (boxed warning: hemolysis in G6PD deficiency)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0ae10bc4-6b65-402f-9db5-2d7753054922"},{"label":"Primaquine phosphate prescribing information, FDA/DailyMed (G6PD testing required; contraindicated in severe deficiency)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8c2bc6-428b-40b6-8114-6df80290878d"},{"label":"Krintafel (tafenoquine) prescribing information, FDA/DailyMed (G6PD testing required; contraindicated in deficiency or unknown status)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cf989d5-36f5-4561-a30b-9fcb9deb6b6a"}],"related_blog":"/blog/pharmacogenomics-europe-guide/","disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information."},"meta":{"disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information.","api_version":"2026-09-20","docs":"https://deepdna.ai/docs/","status":"live","data_as_of":"2026-10-25T21:32:19.251Z","freshness":"https://deepdna.ai/api/v1/freshness"}}