What is gene HFE?
The HFE gene provides instructions for producing a protein that is located on the surface of cells, primarily liver and intestinal cells. The HFE protein is also found on some immune system cells. The HFE protein interacts with other proteins on the cell surface to detect the amount of iron in the body.
What is hemochromatosis HFE gene mutation?
Gene mutations that cause hemochromatosis A gene called HFE is most often the cause of hereditary hemochromatosis. You inherit one HFE gene from each of your parents. The HFE gene has two common mutations, C282Y and H63D. Genetic testing can reveal whether you have these mutations in your HFE gene.
How common is HFE gene mutation?
The most prevalent disease-causing HFE mutation in the general population is the 845G polymorphism, which causes a p. Cys282Tyr amino acid substitution (C282Y) in the HFE protein. Today, approximately 0.4% of Caucasians carry a homozygous23,24 and approximately 6% a heterozygous HFE C282Y mutation.
How long is the HFE gene?
The HFE gene contains 7 exons spanning 12 kb. The full-length transcript represents 6 exons. HFE protein is composed of 343 amino acids.
Is C282Y an allele?
The C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution.
What is homozygous C282Y mutation?
Hereditary hemochromatosis is associated with mutations in the HFE gene. Between 60 and 93 percent of patients with the disorder are homozygous for a mutation designated C282Y.
How big is the HFE gene?
How many HFE genes are there?
Two of the 37 allelic variants of HFE described to date (C282Y and H63D) are significantly correlated with HHC.
Where is the HFE gene located on the chromosome?
The HFE gene is a major histocompatibility complex (MHC) class I–like gene and is located on the short arm of chromosome 6 telomeric to the A3 MHC class 1 histocompatibility locus. Homozygous mutation of C282Y accounts for approximately 85% to 90% of individuals with HH.
What is the function of the HFE protein?
The HFE protein is also found on some immune system cells. The HFE protein interacts with other proteins on the cell surface to detect the amount of iron in the body. When the HFE protein is attached (bound) to a protein called transferrin receptor 1, the receptor cannot bind to a protein called transferrin.
What is the role of the H63D polymorphism in amyotrophic lateral sclerosis (ALS)?
The possible role of the H63D polymorphism in ALS is unclear. In a human neuronal cell line transfected with genes carrying the HFE mutations, the H63D polymorphism induced a decreased expression of SOD1, α‐tubulin and β‐actin; these events can cause a disruption of axonal transport, a factor implicated in ALS pathogenesis.
What is the role of the HFE in the pathogenesis of iron deficiency?
The HFE indirectly regulates the production of an important protein called hepcidin which is believed to be an iron specific regulatory hormone, acting as a sensor of hepatocyte iron levels and hepcidin upstream regulator.