top of page

Deficiency and overload


Iron is involved in energy production and oxygen transport throughout the body, as part of the blood hemoglobin, and muscles’ myoglobin. Low levels of iron may lead to anemia, while iron overload is toxic to the organs.


Genetic variation is responsible for most of the iron overload cases, and up to half the cases of iron deficiencies.



Iron is an essential mineral for the human body. Iron deficiency is quite common. It hampers oxygen supply to tissues by limiting hemoglobin production (anemia) . Excess iron levels on the other hand is less common. Buildup of iron in the body can cause damage to the liver, heart, and pancreas. Iron overload is highly genetic, while iron deficiency has both environmental and genetic backgrounds.

Gene-Wide Association studies analyzed ten of thousands of subjects to find that variation on the HFE and TMPRSS6 genes are the most common and relevant mutations associated with iron levels, as can be seen in this Manhattan plot:


Genomic coordinates (GRCh38): 22:37,065,435-37,109,700


TMPRSS6 has an inhibitory effect on the production of hepcidin. Hepcidin is a liver-derived peptide that regulates iron absorption and iron recycling. Upregulation of hepcidin directly leads to decreased iron absorption from the intestine and decreased iron recycling from macrophages. Polymorphisms in TMPRSS6 were found to be associated with a variety of iron traits, including lower iron and hemoglobin levels, causing iron-refractory iron-deficiency anemia (IRIDA).


Anemia is a worldwide blood disorder affecting about one-quarter of the world's population, especially pregnant women and young children due to their high iron requirements. A number of conditions are associated with anemia, including nutritional or absorptional deficiency, infectious diseases, blood loss caused by menstruation or parasitic diseases and genetic mutations. Iron-deficiency anemia (IDA) is the most common type of anemia and is caused by inadequate iron availability for hemoglobin production, due to the lack of dietary iron or insufficient uptake of iron. In all, about half of anemia cases result from iron deficiency. Studies found that between a quarter to half of the iron deficiency cases are due to genetic factors.

Gene: HFE

Genomic coordinates (GRCh38): 6:26,087,280-26,096,215


Variations in the HFE gene may result in Hemochromatosis Type 1, leading to excess iron deposition in organs. Associated disease appear in later stages of life and include cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism.

Among the 2.2% of Caucasians that carry the risk genotype, there is a 1 to 4 chances for actually accumulating dangerous iron levels. Signs of disease usually start at early 50’s for men, and early 60’s for women.

Variant carriers should limit their iron intake as early as possible, and follow serum levels by periodic blood testing.

Genetic testing for genetic variation/polymorphism (SNP) in genes  associated to iron deficiency and iron overload
bottom of page