Most inherited iron overload is explained by haemochromatosis caused by C282Y homozygosity in the HFE gene. Rarely, iron overload may be caused by private variants in HFE, variants in a number of non-HFE genes or through digenic inheritance.

Hereditary haemochromatosis is an autosomal recessive condition leading to increased iron absorption, its accumulation in the body (biochemical penetrance) and resulting in multiorgan damage (clinical penetrance).