Homeostatic iron regulator protein (HFE)

Homeostatic iron regulator protein (HFE) is a major histocompatibility complex class I-like protein that is primarily expressed in liver, intestinal crypt cells, and some immune cells. It plays a crucial role in systemic iron homeostasis by influencing iron absorption and regulating the expression of hepcidin, the key hormone controlling iron metabolism. The HFE protein interacts with transferrin receptor 1 (TFRC) to regulate the uptake and release of iron by cells. When bound to TFRC, HFE modulates transferrin-iron interactions and inhibits excessive iron uptake. It also regulates the production of hepcidin, which in turn controls dietary iron absorption and iron release from storage sites. Mutations in the HFE gene, particularly C282Y and H63D, are associated with hereditary hemochromatosis, a genetic disorder characterized by excessive iron accumulation and associated organ dysfunction. HFE's molecular, structural, and functional attributes make it a critical node in iron regulation and a relevant target in iron metabolism disorders.

Other names

Hereditary hemochromatosis proteinHFEHLA-HHFE1HHMVCD7TFQTL2Major histocompatibility complex class I-like protein HFEHigh Fe

Drugs used in hereditary hemochromatosis (e.g., phlebotomy, iron chelators) decrease total body iron burden; their action does not directly involve HFE, but mitigates the effects of HFE loss-of-function