SLC40A1

The SLC40A1 gene provides instructions for making a protein called ferroportin 1. This protein plays an essential role in the regulation of iron levels in the body. Iron from the diet is absorbed through the walls of the small intestine. Ferroportin 1 then transports iron from the small intestine into the bloodstream. In the bloodstream, the iron binds to another transport protein called transferrin that carries it to the tissues and organs of the body. Ferroportin 1 also transports iron out of specialized immune system cells (called reticuloendothelial cells) that are found in the liver, spleen, and bone marrow. The iron balance in the body is regulated by the amount of iron stored and released from these cells.

Research suggests that another iron regulatory protein, hepcidin, controls the amount of ferroportin 1 available to transport iron out of cells. Hepcidin binds to ferroportin and causes it to be broken down when the body's iron supplies are adequate. When the body is lacking iron, hepcidin levels drop and more ferroportin 1 is available to bring iron into the body and to release it from storage.

hemochromatosis - caused by mutations in the SLC40A1 gene

Researchers have identified approximately 15 mutations that cause type 4 hemochromatosis. Almost all of these mutations change a single protein building block (amino acid) in ferroportin 1. Abnormal versions of ferroportin 1 do not permit the normal transport and release of iron from intestinal or reticuloendothelial cells. As a result, the regulation of iron levels in the body is impaired and iron overload results. One mutated copy of this gene in each cell is sufficient to cause type 4 hemochromatosis, sometimes referred to as ferroportin disease.