Details on the HFE Gene

What is the official name of the HFE gene?

The official name of this gene is “hemochromatosis.”

HFE is the gene’s official symbol. The HFE gene is also known by other names, listed below.

What is the normal function of the HFE gene?

The HFE gene provides instructions for producing a protein that is located mainly on the surface of intestinal cells, liver cells, and some cells in the immune system. During digestion, this protein helps certain cells regulate the absorption of iron into the small intestine by interacting with other proteins located on the cell surface. The body uses this mechanism to help monitor its supply of iron. When the proteins involved in iron sensing and absorption are functioning properly, the body absorbs only about 10 percent of the iron ingested in the diet.

Research suggests that the HFE protein also helps control levels of another important iron regulatory protein, hepcidin. Adequate levels of hepcidin are necessary to ensure that the body does not absorb and store too much iron in its tissues and organs.

How are changes in the HFE gene related to health conditions?

hemochromatosis – caused by mutations in the HFE gene
Researchers have identified more than 20 mutations in the HFE gene that cause type 1 hemochromatosis. These mutations alter the size of the HFE protein or disrupt its 3-dimensional shape. As a result, the HFE protein cannot function properly. Two particular mutations are responsible for most cases of type 1 hemochromatosis. Each of these mutations changes one of the building blocks (amino acids) used to make the HFE protein. The most common mutation replaces the amino acid cysteine with the amino acid tyrosine at position 282 in the protein’s chain of amino acids (written as C282Y or Cys282Tyr). The other mutation replaces the amino acid histidine with the amino acid aspartic acid at position 63 (written as H63D or His63Asp). As a result of these substitutions, the altered protein is not sent to the cell surface and does not interact with a cell surface receptor called the transferrin receptor. The transferrin receptor plays a critical role in regulating the amount of iron that enters the cell. When the HFE protein does not bind to the transferrin receptor, too much iron enters the body through the cells of the small intestine. This increased absorption of iron leads to the iron overload characteristic of this disorder.
porphyria – increased risk from variations of the HFE gene

Mutations in the HFE gene that cause hemochromatosis are also believed to increase the risk of developing a form of porphyria called porphyria cutanea tarda. These mutations have been found more frequently in people with this condition than in unaffected people. Researchers are not certain how mutations in the HFE gene are related to the signs and symptoms of porphyria cutanea tarda. These mutations likely trigger this condition by increasing iron levels in the liver, as in hemochromatosis.

X-linked sideroblastic anemia – course of condition modified by mutations in the HFE gene
One particular mutation in the HFE gene may increase the severity of symptoms in X-linked sideroblastic anemia when it is present in patients who also have mutations in the ALAS2 gene. The mutation results in a substitution of the amino acid tyrosine for the amino acid cysteine at position 282 (written as C282Y or Cys282Tyr) in the HFE protein. Although it is not known exactly how the mutation affects symptoms, it may cause iron to build up more rapidly in the body’s tissues.

Where is the HFE gene located?

Cytogenetic Location: 6p21.3

Molecular Location on chromosome 6: base pairs 26,195,426 to 26,205,037

The HFE gene is located on the short (p) arm of chromosome 6 at position 21.3.

More precisely, the HFE gene is located from base pair 26,195,426 to base pair 26,205,037 on chromosome 6.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about HFE?

You and your healthcare professional may find the following resources about HFE helpful.

  • Gene Reviews – Clinical summary (http://www.genetests.org/query?dz=hemochromatosis)
  • Gene Tests – DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=2242)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed – Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search& DB=PubMed&term= (HFE+gene[TIAB])+AND+english[la]+AND+human[mh] &orig_db= PubMed& filters=ON&pmfilter_EDatLimit=720+Days)
  • OMIM – Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=235200)
  • Research Resources – Tools for researchers
    • CDC: Genomics and Disease Prevention (GDPInfo) (http://www2a.cdc.gov/genomics/GDPQueryTool/GeneSearch.asp? GeneSymbol=HFE)
    • Entrez Gene (http://view.ncbi.nlm.nih.gov/gene/3077)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp?HFE)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id= 4886)

What other names do people use for the HFE gene or gene products?

  • hemochromatosis, genetic; GH
  • Hemochromatosis, Hereditary; HH
  • HFE_HUMAN
  • HHC
  • HLA-H antigen

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding HFE?

acids ; amino acid ; anemia ; antigens ; cell ; digestion ; gene ; GH ; HLA ; immune system ; intestine ; iron ; metabolism ; mutation ; protein ; receptor ; sign ; substitution ; symptom ; tissue ; transferrin ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

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  • NIDDK fact sheet on hemochromatosis (http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm)
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