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ALAS2

Reviewed October 2006

What is the official name of the ALAS2 gene?

The official name of this gene is “aminolevulinate, delta-, synthase 2.”

ALAS2 is the gene's official symbol. The ALAS2 gene is also known by other names, listed below.

What is the normal function of the ALAS2 gene?

The ALAS2 gene provides instructions for the production of an enzyme called delta-aminolevulinate synthase 2 (ALA-synthase). ALAS2 is one of two genes that carry instructions for making this enzyme. The ALAS2 gene makes a version of ALA-synthase that is produced only in developing red blood cells (sideroblasts). The other gene that makes this enzyme, ALAS1, is turned on in all tissues in the body. ALA-synthase carries out a step in the production of heme, the iron-containing part of hemoglobin. Hemoglobin is the oxygen-carrying protein in red blood cells. The activity of ALA-synthase determines how much heme, and therefore how much hemoglobin, will be produced by red blood cells.

Heme production is a multistep process, and each step is controlled by a different enzyme. The first step in the production of heme is the manufacture of a compound called delta-aminolevulinic acid (ALA), which is achieved through the action of ALA-synthase. Seven other enzymes will modify this compound before it becomes heme. The heme molecule is then incorporated into hemoglobin and packaged into red blood cells.

How are changes in the ALAS2 gene related to health conditions?

X-linked sideroblastic anemia - caused by mutations in the ALAS2 gene

More than 25 mutations that cause X-linked sideroblastic anemia have been identified in the ALAS2 gene. These mutations prevent the normal production of heme and result in reduced levels of hemoglobin in the blood. Because there is not enough hemoglobin to incorporate iron, excess iron builds up in sideroblasts. The signs and symptoms of X-linked sideroblastic anemia are a result of low hemoglobin levels and a buildup of iron in the body's tissues.

Where is the ALAS2 gene located?

Cytogenetic Location: Xp11.21

Molecular Location on the X chromosome: base pairs 55,052,216 to 55,074,135

The ALAS2 gene is located on the short (p) arm of the X chromosome at position 11.21.

The ALAS2 gene is located on the short (p) arm of the X chromosome at position 11.21.

More precisely, the ALAS2 gene is located from base pair 55,052,216 to base pair 55,074,135 on the X chromosome.

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 ALAS2?

You and your healthcare professional may find the following resources about ALAS2 helpful.

  • Educational resources - Information pages
    Harvard University Information Center for Sickle Cell and Thalassemic Disorders: Sideroblastic Anemias (http://sickle.bwh.harvard.edu/sideroblastic.html)

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=((ALAS2[TIAB])+OR+(ALA-synthase[TIAB])+OR+(5-aminolevulinate+synthase[TIAB]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=3600+Days)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=301300)
  • Research Resources - Tools for researchers
    • Entrez Gene (http://view.ncbi.nlm.nih.gov/gene/212)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp?ALAS2)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=397)

What other names do people use for the ALAS2 gene or gene products?

  • ALAS-E
  • ALAS, erythroid
  • 5-aminolevulinate synthase, erythroid-specific, mitochondrial
  • aminolevulinate, delta-, synthase 2 (sideroblastic/hypochromic anemia)
  • 5-aminolevulinic acid synthase
  • ANH1
  • ASB
  • Delta-ALA synthetase
  • Delta-aminolevulinate synthase
  • HEM0_HUMAN

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 ALAS2?

acids ; anemia ; cell ; compound ; enzyme ; gene ; heme ; hemoglobin ; hypochromic ; iron ; molecule ; mutation ; oxygen ; protein ; red blood cell ; sideroblast ; sign ; symptom ; synthetases ; tissue

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

References
  • Ajioka RS, Phillips JD, Kushner JP. Biosynthesis of heme in mammals. Biochim Biophys Acta. 2006 Jul;1763(7):723-36. Epub 2006 Jun 3. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16839620)
  • Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW. Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16121195)
  • Bekri S, May A, Cotter PD, Al-Sabah AI, Guo X, Masters GS, Bishop DF. A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. Blood. 2003 Jul 15;102(2):698-704. Epub 2003 Mar 27. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12663458)
  • Cox TC, Sadlon TJ, Schwarz QP, Matthews CS, Wise PD, Cox LL, Bottomley SS, May BK. The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis. Int J Biochem Cell Biol. 2004 Feb;36(2):281-95. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14643893)
  • Furuyama K, Harigae H, Heller T, Hamel BC, Minder EI, Shimizu T, Kuribara T, Blijlevens N, Shibahara S, Sassa S. Arg452 substitution of the erythroid-specific 5-aminolaevulinate synthase, a hot spot mutation in X-linked sideroblastic anaemia, does not itself affect enzyme activity. Eur J Haematol. 2006 Jan;76(1):33-41. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16343269)
  • Goncalves P, Pereira JC, Rebelo U, Ribeiro ML. Gene symbol: ALAS2. Disease: sideroblastic anaemia. Hum Genet. 2004 Nov;115(6):531. Epub 2004 Nov 24. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15565468)
  • May A, Bishop DF. The molecular biology and pyridoxine responsiveness of X-linked sideroblastic anaemia. Haematologica. 1998 Jan;83(1):56-70. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=9542324)
  • Roy CN, Andrews NC. Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum Mol Genet. 2001 Oct 1;10(20):2181-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11673399)
  • Sadlon TJ, Dell'Oso T, Surinya KH, May BK. Regulation of erythroid 5-aminolevulinate synthase expression during erythropoiesis. Int J Biochem Cell Biol. 1999 Oct;31(10):1153-67. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10582344)
  • Shoolingin-Jordan PM, Al-Daihan S, Alexeev D, Baxter RL, Bottomley SS, Kahari ID, Roy I, Sarwar M, Sawyer L, Wang SF. 5-Aminolevulinic acid synthase: mechanism, mutations and medicine. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):361-6. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12686158)
  • Whatley SD, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton MN, Elder GH, Holme SA, Anstey AV, Parker M, Corrigall AV, Meissner PN, Hift RJ, Marsden JT, Ma Y, Mieli-Vergani G, Deybach JC, Puy H. C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet. 2008 Sep;83(3):408-14. Epub 2008 Sep 4. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=18760763)

 

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 2006
Published: January 23, 2009