HFE and Tangier disease: The HFE gene (homeostatic iron regulator, chromosome 6p23.1) [1] that encodes HFE, a negative upstream regulator of hepcidin [2], and two common non-ancestral HFE alleles p.C282Y (c.845G>A; rs1800562) and p.H63D (c.187C>G; rs1799545) were discovered in referred white patients with hemochromatosis and iron overload (IO) in 1996 [1].