Reviewed July 2009
What is the official name of the ALAS2 gene?
The official name of this gene is “5'-aminolevulinate 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 making an enzyme called 5'-aminolevulinate synthase 2 or erythroid ALA-synthase. This version of the enzyme is found only in developing red blood cells called erythroblasts.
ALA-synthase plays an important role in the production of heme. Heme is a component of iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood). Heme is vital for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver.
The production of heme is a multi-step process that requires eight different enzymes. ALA-synthase is responsible for the first step in this process, the formation of a compound called delta-aminolevulinic acid (ALA). In subsequent steps, seven other enzymes produce and modify compounds that ultimately lead to heme.
How are changes in the ALAS2 gene related to health conditions?
- porphyria - caused by mutations in the ALAS2 gene
At least two ALAS2 gene mutations have been found in people with a form of porphyria known as X-linked dominant erythropoietic protoporphyria. Each of these mutations deletes a small amount of genetic material near the end of the ALAS2 gene. These changes overactivate erythroid ALA-synthase, which increases the production of ALA within red blood cells. The excess ALA is converted by other enzymes to compounds called porphyrins. If these compounds build up in erythroblasts, they can leak out and be transported through the bloodstream to the skin and other tissues. High levels of porphyrins in the skin cause the oversensitivity to sunlight that is characteristic of this condition.
- X-linked sideroblastic anemia - caused by mutations in the ALAS2 gene
At least 50 mutations that cause X-linked sideroblastic anemia have been identified in the ALAS2 gene. Almost all of these mutations change single protein building blocks (amino acids) in erythroid ALA-synthase. These changes impair the activity of the enzyme, which disrupts the normal production of heme in developing red blood cells. A reduction in the amount of heme prevents these cells from making enough hemoglobin. Because almost all of the iron transported into erythroblasts is normally incorporated into heme, the reduced production of heme leads to a buildup of excess iron in these cells. Additionally, the body attempts to compensate for the hemoglobin shortage by absorbing more iron from the diet. This buildup of excess iron can damage the body's organs. Low hemoglobin levels and the resulting accumulation of iron in the body's organs lead to the characteristic features of X-linked sideroblastic anemia.
Where is the ALAS2 gene located?
Cytogenetic Location: Xp11.21
Molecular Location on the X chromosome: base pairs 55,009,054 to 55,031,063
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 55,009,054 to base pair 55,031,063 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.
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/pubmed?term=%28%28ALAS2%5BTIAB%5D%29%20OR%20%28ALA-synthase%5BTIAB%5D%29%20OR%20%285-aminolevulinate%20synthase%5BTIAB%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/301300)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_ALAS2.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=397)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/212)
What other names do people use for the ALAS2 gene or gene products?
- 5-aminolevulinate synthase, erythroid-specific, mitochondrial
- ALAS, erythroid
- aminolevulinate, delta-, synthase 2
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?
bone marrow ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Ajioka RS, Phillips JD, Kushner JP. Biosynthesis of heme in mammals. Biochim Biophys Acta. 2006 Jul;1763(7):723-36. Epub 2006 Jun 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16839620?dopt=Abstract)
- 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/pubmed/16121195?dopt=Abstract)
- 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/pubmed/12663458?dopt=Abstract)
- Bottomley SS. Congenital sideroblastic anemias. Curr Hematol Rep. 2006 Mar;5(1):41-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16537045?dopt=Abstract)
- 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/pubmed/14643893?dopt=Abstract)
- 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/pubmed/16343269?dopt=Abstract)
- 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/pubmed/9542324?dopt=Abstract)
- Nakajima O, Okano S, Harada H, Kusaka T, Gao X, Hosoya T, Suzuki N, Takahashi S, Yamamoto M. Transgenic rescue of erythroid 5-aminolevulinate synthase-deficient mice results in the formation of ring sideroblasts and siderocytes. Genes Cells. 2006 Jun;11(6):685-700. (http://www.ncbi.nlm.nih.gov/pubmed/16716198?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/212)
- Nemeth E. Iron regulation and erythropoiesis. Curr Opin Hematol. 2008 May;15(3):169-75. doi: 10.1097/MOH.0b013e3282f73335. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18391780?dopt=Abstract)
- 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/pubmed/10582344?dopt=Abstract)
- 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/pubmed/12686158?dopt=Abstract)
- 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. doi: 10.1016/j.ajhg.2008.08.003. Epub 2008 Sep 4. (http://www.ncbi.nlm.nih.gov/pubmed/18760763?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.