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Genetics Home Reference: your guide to understanding genetic conditions
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SLC40A1

Reviewed October 2012

What is the official name of the SLC40A1 gene?

The official name of this gene is “solute carrier family 40 (iron-regulated transporter), member 1.”

SLC40A1 is the gene's official symbol. The SLC40A1 gene is also known by other names, listed below.

What is the normal function of the SLC40A1 gene?

The SLC40A1 gene provides instructions for making a protein called ferroportin. This protein is involved in the process of iron absorption in the body. Iron from the diet is absorbed through the walls of the small intestine. Ferroportin then transports iron from the small intestine into the bloodstream, and 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 by the body depends on the amount of iron stored and released from intestinal and reticuloendothelial cells.

Research suggests that the amount of ferroportin available to transport iron out of cells is controlled by another iron regulatory protein, hepcidin. Hepcidin binds to ferroportin and causes it to be broken down when the body's iron supplies are adequate. When the body is lacking iron, hepcidin levels drop and more ferroportin is available to bring iron into the body and to release it from storage.

Does the SLC40A1 gene share characteristics with other genes?

The SLC40A1 gene belongs to a family of genes called SLC (solute carriers).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the SLC40A1 gene related to health conditions?

hemochromatosis - caused by mutations in the SLC40A1 gene

Researchers have identified approximately 15 mutations in the SLC40A1 gene that cause a form of iron overload called ferroportin disease, which is also sometimes referred to as type 4 hemochromatosis. Almost all of these mutations change a single protein building block (amino acid) in ferroportin. Abnormal versions of ferroportin do not permit the normal transport and release of iron from intestinal or reticuloendothelial cells. As a result, the regulation of iron levels in the body is impaired and iron overload results. One mutated copy of this gene in each cell is sufficient to cause ferroportin disease.

African iron overload - associated with the SLC40A1 gene

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 gender 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 Q248H or Gln248His. 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.

Where is the SLC40A1 gene located?

Cytogenetic Location: 2q32

Molecular Location on chromosome 2: base pairs 189,560,589 to 189,583,751

The SLC40A1 gene is located on the long (q) arm of chromosome 2 at position 32.

The SLC40A1 gene is located on the long (q) arm of chromosome 2 at position 32.

More precisely, the SLC40A1 gene is located from base pair 189,560,589 to base pair 189,583,751 on chromosome 2.

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 SLC40A1?

You and your healthcare professional may find the following resources about SLC40A1 helpful.

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

What other names do people use for the SLC40A1 gene or gene products?

  • 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

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 SLC40A1?

amino acid ; bone marrow ; carrier ; cell ; gene ; glutamine ; histidine ; immune system ; inherit ; intestine ; iron ; metabolism ; protein ; protein sequence ; proton ; solute

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

References

  • Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and overload. Hematology Am Soc Hematol Educ Program. 2003:40-61. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14633776?dopt=Abstract)
  • Beutler E. Hemochromatosis: genetics and pathophysiology. Annu Rev Med. 2006;57:331-47. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16409153?dopt=Abstract)
  • De Domenico I, Ward DM, Musci G, Kaplan J. Iron overload due to mutations in ferroportin. Haematologica. 2006 Jan;91(1):92-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16434376?dopt=Abstract)
  • De Domenico I, Ward DM, Nemeth E, Vaughn MB, Musci G, Ganz T, Kaplan J. The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8955-60. Epub 2005 Jun 13. (http://www.ncbi.nlm.nih.gov/pubmed/15956209?dopt=Abstract)
  • Deicher R, Hörl WH. New insights into the regulation of iron homeostasis. Eur J Clin Invest. 2006 May;36(5):301-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16634833?dopt=Abstract)
  • Devalia V, Carter K, Walker AP, Perkins SJ, Worwood M, May A, Dooley JS. Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). Blood. 2002 Jul 15;100(2):695-7. (http://www.ncbi.nlm.nih.gov/pubmed/12091367?dopt=Abstract)
  • Fleming RE, Sly WS. Ferroportin mutation in autosomal dominant hemochromatosis: loss of function, gain in understanding. J Clin Invest. 2001 Aug;108(4):521-2. (http://www.ncbi.nlm.nih.gov/pubmed/11518724?dopt=Abstract)
  • Fleming RE. Advances in understanding the molecular basis for the regulation of dietary iron absorption. Curr Opin Gastroenterol. 2005 Mar;21(2):201-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15711214?dopt=Abstract)
  • Kelleher T, Ryan E, Barrett S, Sweeney M, Byrnes V, O'Keane C, Crowe J. Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in hereditary haemochromatosis. Gut. 2004 Aug;53(8):1174-9. (http://www.ncbi.nlm.nih.gov/pubmed/15247188?dopt=Abstract)
  • McGregor J, McKie AT, Simpson RJ. Of mice and men: genetic determinants of iron status. Proc Nutr Soc. 2004 Feb;63(1):11-20. (http://www.ncbi.nlm.nih.gov/pubmed/15070436?dopt=Abstract)
  • McKie AT, Barlow DJ. The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1). Pflugers Arch. 2004 Feb;447(5):801-6. Epub 2003 Jun 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12836025?dopt=Abstract)
  • McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell. 2000 Feb;5(2):299-309. (http://www.ncbi.nlm.nih.gov/pubmed/10882071?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/30061)
  • Pietrangelo A. Hereditary hemochromatosis--a new look at an old disease. N Engl J Med. 2004 Jun 3;350(23):2383-97. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15175440?dopt=Abstract)
  • Pietrangelo A. Non-HFE hemochromatosis. Semin Liver Dis. 2005 Nov;25(4):450-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16315138?dopt=Abstract)
  • Rivers CA, Barton JC, Gordeuk VR, Acton RT, Speechley MR, Snively BM, Leiendecker-Foster C, Press RD, Adams PC, McLaren GD, Dawkins FW, McLaren CE, Reboussin DM. Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Blood Cells Mol Dis. 2007 May-Jun;38(3):247-52. Epub 2007 Feb 5. (http://www.ncbi.nlm.nih.gov/pubmed/17276706?dopt=Abstract)
  • Thomas C, Oates PS. Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes. Gut. 2004 Jan;53(1):44-9. (http://www.ncbi.nlm.nih.gov/pubmed/14684575?dopt=Abstract)
  • Wallace DF, Pedersen P, Dixon JL, Stephenson P, Searle JW, Powell LW, Subramaniam VN. Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis. Blood. 2002 Jul 15;100(2):692-4. (http://www.ncbi.nlm.nih.gov/pubmed/12091366?dopt=Abstract)
  • Zaahl MG, Merryweather-Clarke AT, Kotze MJ, van der Merwe S, Warnich L, Robson KJ. Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload. Hum Genet. 2004 Oct;115(5):409-17. Epub 2004 Aug 24. (http://www.ncbi.nlm.nih.gov/pubmed/15338274?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2012
Published: December 16, 2014