SLC40A1

Researchers have identified more than 37 mutations in the SLC40A1 gene that cause a form of hereditary hemochromatosis called ferroportin disease, which is also sometimes referred to as type 4 hemochromatosis. This form of the disorder usually begins during adulthood. Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron accumulates in, and eventually damages, the body's tissues and organs.

Almost all SLC40A1 gene mutations change a single protein building block (amino acid) in ferroportin. Abnormal ferroportin proteins cannot transport and release iron from intestinal or reticuloendothelial cells. As a result, the regulation of iron levels in the body is impaired, resulting in iron overload and damage to tissues and organs in the body that is characteristic of hereditary hemochromatosis.

Some studies have indicated that a particular variation in the SLC40A1 gene slightly increases the risk of increased iron stores in people of African descent, which may lead to African iron overload. This effect seems to be more pronounced in men, which may be related to sex differences in the processing of iron.

The SLC40A1 gene variation associated with increased iron stores replaces the amino acid glutamine with the amino acid histidine at position 248 in the ferroportin protein sequence and is written as Gln248His or Q248H. It is found in 5 to 20 percent of people of African descent but is not generally found in other populations. The Q248H variation may affect the way ferroportin helps to regulate iron levels in the body, resulting in an increased risk of African iron overload. People with the variation may inherit an increased risk of this condition, but not the condition itself. Not all people with this condition have the variation in the gene, and not all people with the variation will develop the disorder.