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SLC40A1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SLC40A1 gene

The SLC40A1 gene encodes ferroportin, a protein vital for regulating iron absorption and distribution throughout the body.

Normal Function

The SLC40A1 gene provides instructions for making a protein called ferroportin. This protein is involved in the process of absorbing iron that the body receives from food. Ferroportin transports iron obtained from the diet that is absorbed through the walls of the small intestine into the bloodstream. The iron is carried by the blood to the tissues and organs of the body. Ferroportin also transports iron out of specialized immune system cells (called reticuloendothelial cells) that are found in the liver, spleen, and bone marrow. The amount of iron absorbed during digestion depends on the amount of iron transported from intestinal and reticuloendothelial cells.

The amount of ferroportin available to transport iron is controlled by another iron regulatory protein, hepcidin. Hepcidin attaches (binds) to ferroportin and causes it to be broken down when the body's iron supplies are normal. When the body is low on iron, hepcidin levels decrease and more ferroportin is available to transport iron into the bloodstream so it can be delivered to tissues throughout the body.

Health Conditions Related to Genetic Changes

Hereditary hemochromatosis

Researchers have identified more than 37 mutations in the SLC40A1 gene that cause a form of hereditary hemochromatosis called ferroportin disease, which is also sometimes referred to as type 4 hemochromatosis. This form of the disorder usually begins during adulthood. Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron accumulates in, and eventually damages, the body's tissues and organs.

Almost all SLC40A1 gene mutations change a single protein building block (amino acid) in ferroportin. Abnormal ferroportin proteins cannot transport and release iron from intestinal or reticuloendothelial cells. As a result, the regulation of iron levels in the body is impaired, resulting in iron overload and damage to tissues and organs in the body that is characteristic of hereditary hemochromatosis.

African iron overload

Some studies have indicated that a particular variation in the SLC40A1 gene slightly increases the risk of increased iron stores in people of African descent, which may lead to African iron overload. This effect seems to be more pronounced in men, which may be related to sex differences in the processing of iron.

The SLC40A1 gene variation associated with increased iron stores replaces the amino acid glutamine with the amino acid histidine at position 248 in the ferroportin protein sequence and is written as Gln248His or Q248H. It is found in 5 to 20 percent of people of African descent but is not generally found in other populations. The Q248H variation may affect the way ferroportin helps to regulate iron levels in the body, resulting in an increased risk of African iron overload. People with the variation may inherit an increased risk of this condition, but not the condition itself. Not all people with this condition have the variation in the gene, and not all people with the variation will develop the disorder.

Other Names for This Gene

  • Ferroportin 1
  • FPN1
  • HFE4
  • IREG1
  • Iron regulated gene 1
  • Iron-regulated transporter 1
  • MTP1
  • S40A1_HUMAN
  • SLC11A3
  • Solute carrier family 11 (proton-coupled divalent metal ion transporters), member 3
  • solute carrier family 40 (iron-regulated transporter), member 1

Genomic Location

The SLC40A1 gene is found on chromosome 2.

Frequently Asked Questions

Diagnosis usually starts with routine blood tests that show elevated serum ferritin and transferrin saturation. If iron overload is suspected, a liver MRI or biopsy may be performed to assess iron deposition. Genetic testing for pathogenic variants in the SLC40A1 gene confirms the diagnosis and distinguishes ferroportin disease from other forms of hereditary hemochromatosis.
Yes, dietary iron intake can affect iron overload. Patients are advised to limit heme iron sources (red meat, organ meats) and avoid iron‑fortified cereals or supplements unless prescribed. Non‑heme iron from plant foods is less readily absorbed, especially when consumed with calcium‑rich foods or polyphenol‑rich beverages (tea, coffee). Vitamin C enhances iron absorption, so large doses should be taken apart from iron‑rich meals. A balanced diet rich in fruits, vegetables, and whole grains helps maintain overall health without adding excess iron.
Most pathogenic SLC40A1 variants are inherited in an autosomal‑dominant manner, meaning a single copy of the mutated gene can cause disease. Each child of an affected parent has a 50 % chance of inheriting the mutation. However, penetrance is variable; some carriers develop significant iron overload while others remain asymptomatic. Genetic counseling and cascade testing of family members are recommended to identify at‑risk relatives early.
Therapeutic phlebotomy (regular removal of blood) is the first‑line treatment for most patients because it safely reduces body iron stores. In cases where phlebotomy is contraindicated (e.g., anemia), iron‑chelating agents such as deferasirox or deferoxamine may be used under specialist supervision. Lifestyle measures, including limiting dietary iron and avoiding vitamin C supplements that increase iron absorption, support medical therapy.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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