Overview
The HFE gene regulates iron absorption from food. Mutations can lead to excessive iron storage in the body, which, if untreated, results in tissue damage.
6p22.2 (Chromosome 6)
Hereditary Diseases / Metabolism
Autosomal recessive
C282Y carrier frequency approx. 1:10 (Northern Europe)
Function & Significance
The HFE protein interacts with transferrin receptors on the cell surface to control the amount of iron absorbed into cells (particularly in the liver and intestine).
When certain mutations are present, the protein loses its regulatory function. The body “thinks” it is suffering from an iron deficiency and absorbs iron from food uncontrollably, which then deposits in the organs.
🔬 The C282Y Mutation
The C282Y mutation (rs1800562) is the most clinically significant variant. Nearly 90% of all patients with classical hemochromatosis are homozygous (carry two copies) for this mutation.
Associated Diseases
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🩸 Hereditary Hemochromatosis
Iron storage disease Type 1
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🌳 Liver Cirrhosis
Long-term consequence of massive iron deposition
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🍯 Bronze Diabetes
Combination of skin discoloration and diabetes due to pancreatic damage
🧬 Relevant SNPs
6:26092913
/
Significance: C282Y – AA genotype leads to a very high risk of iron overload.
6:26091179
/
Significance: H63D – Moderately increases risk, usually only clinically relevant in combination with C282Y.
⚕️ Clinical Recommendation
If risk genotypes are detected, ferritin levels and transferrin saturation in the blood should be measured regularly. Early treatment through phlebotomy (bloodletting) can completely prevent organ damage.
📚 Data Sources
- OMIM: #235200 (Hemochromatosis)
- dbSNP: rs1800562, rs1799945
- ClinVar: Pathogenic HFE variants
- PubMed: Literature on iron homeostasis
Biological Function
Associated Conditions
Analyzed Markers
C282Y - Main mutation; AA (homozygous) often leads to clinical hemochromatosis.
H63D - Moderate risk, especially combined with C282Y.
S65C - Rarer variant, minor clinical effect.