G6PD
G6PD is the enzyme that shields your red blood cells from oxidative damage. Inherited deficiency is the most common enzyme defect in humans — roughly 400 million people carry it — and it usually causes no symptoms until a trigger appears: fava beans, an infection, or certain medications. Then red cells can break down (hemolysis), sometimes seriously. Because the gene is on the X chromosome, it affects men more often than women.
The antioxidant shield for red blood cells.
G6PD runs the first step of the pentose phosphate pathway, generating NADPH — the molecule red blood cells rely on to keep their antioxidant defenses (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 deficiency is not a daily problem; most people never know they have it until a specific trigger appears. The three classic categories of trigger are certain drugs, fava beans (giving the condition its old name, favism), and infection. G6PD deficiency can also cause prolonged newborn jaundice.
The gene sits on the X chromosome, so 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 an intermediate "carrier" whose red cells are a mosaic — which can make enzyme testing in women harder to interpret.
Hundreds of variants, a few that matter most.
More than 200 G6PD variants are known, graded by the World Health Organization from severe (Class I) to normal activity. Two are common enough to dominate the global picture:
Clinically, what matters is the resulting enzyme activity — normal, deficient, or deficient with chronic hemolysis — which is why a quantitative enzyme assay, not a single SNP, is the diagnostic standard.
A genotype that changes what is safe to take.
G6PD deficiency has a CPIC guideline and appears on multiple drug labels. The practical message is about avoidance:
- Rasburicase (used in tumor lysis syndrome) is contraindicated in G6PD deficiency — it can cause severe acute hemolysis and methemoglobinemia. The FDA label recommends screening higher-risk patients first.
- Antimalarials primaquine and tafenoquine require documented G6PD status before use, because they can trigger serious hemolysis in deficient patients.
- Other oxidant drugs — dapsone, nitrofurantoin, methylene blue, and some sulfonamides — carry hemolysis risk and are used with caution.
- Fava beans and oxidative stress — deficient individuals are advised to avoid fava beans, and clinicians watch for hemolysis during infections.
"G6PD deficiency is usually silent. Its value as a genetic result is preventive: knowing it before a doctor prescribes rasburicase or primaquine — not after a hemolytic crisis."
Primary sources: CPIC — G6PD gene page; Gammal et al., Clin Pharmacol Ther 2023 (CPIC G6PD guideline); StatPearls — G6PD deficiency; PharmGKB G6PD.
What consumer arrays do — and don't — tell you about G6PD.
G6PD is a gene where consumer raw data gives partial, ancestry-dependent information:
- rs5030868 (G6PD Mediterranean) — sometimes genotyped; a key variant in Mediterranean, Middle Eastern, and South Asian ancestry.
- rs1050828 (part of G6PD A−) — sometimes genotyped; the common African-ancestry variant.
- Many regional variants (Canton, Kaiping, Viangchan and others) are usually not on consumer chips, so a "normal" raw-data readout can miss real deficiency.
Two extra cautions make this gene special. First, it is X-linked: a heterozygous woman can have intermediate, mosaic activity that genotype alone does not capture. Second, the clinical standard is a quantitative enzyme test, not DNA — genotype is supporting context. If your ancestry or a raw-data variant suggests possible deficiency, that is a reason to ask for an enzyme test before any at-risk medication — not a diagnosis on its own.