hemochromatosis type 2 (juvenile)
The HFE2 gene provides instructions for making a protein called hemojuvelin. This protein is made in the liver, heart, and muscles used for movement (skeletal muscles). Researchers recently discovered that hemojuvelin plays a role in maintaining iron balance in the body. Although its exact function is unclear, hemojuvelin appears to regulate the levels of another protein called hepcidin. Hepcidin also plays a key role in maintaining proper iron levels in the body.
Researchers have identified more than 20 HFE2 gene mutations that cause type 2 hemochromatosis, a form of hereditary hemochromatosis that begins during childhood or adolescence. Most HFE2 gene mutations change one of the protein building blocks (amino acids) used to make hemojuvelin. Most frequently, the amino acid glycine is replaced by the amino acid valine at protein position 320 (written as Gly320Val). Other mutations create a premature stop signal in the instructions for making the hemojuvelin protein. As a result, an abnormally small protein is made.
Mutations in the HFE2 gene lead to an altered hemojuvelin protein that cannot function properly. Without adequate hemojuvelin, levels of the protein hepcidin are reduced and iron balance is disturbed. As a result, too much iron is absorbed during digestion, which leads to iron overload and damage to tissues and organs in the body.
- RGM domain family, member C