Homeostatic iron regulator messenger RNA (HFE mRNA)

Homeostatic iron regulator (HFE) messenger RNA is the transcript of the HFE gene, which encodes a membrane protein essential for the regulation of systemic iron homeostasis. The HFE protein functions as an iron sensor in hepatocytes, where it interacts with transferrin receptors (TfR1 and TfR2) to modulate the expression of hepcidin, the master regulator of iron absorption and distribution. Mutations in the HFE mRNA, most notably the C282Y substitution, lead to deficient hepcidin production, resulting in the excessive iron absorption characteristic of Type 1 hereditary hemochromatosis. As a therapeutic target, HFE mRNA is being explored for mRNA replacement therapies, where lipid nanoparticles deliver functional transcripts to the liver to restore hepcidin levels. Additionally, novel RNA editing technologies aim to correct pathogenic mutations directly within the endogenous HFE mRNA transcript using site-specific oligonucleotides. These approaches represent a shift from traditional iron-depletion methods, such as phlebotomy, toward addressing the underlying molecular cause of iron overload disorders.

Other names

Hereditary hemochromatosis protein mRNAHLA-H mRNAHigh FE2+ mRNAHomeostatic iron regulator transcript

mRNA replacement therapy (restoration of hepatic HFE expression), RNA editing (ADAR-mediated deamination of target adenosine to inosine)