The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ALAS2  -  5'-aminolevulinate synthase 2

Homo sapiens

Synonyms: 5-aminolevulinate synthase, erythroid-specific, mitochondrial, 5-aminolevulinic acid synthase 2, ALAS-E, ALASE, ANH1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ALAS2


High impact information on ALAS2


Chemical compound and disease context of ALAS2


Biological context of ALAS2

  • A 38-year-old male presented with this phenotype (hemoglobin [Hb] 7.6 g/dL, mean corpuscular volume [MCV] 64 fL, serum ferritin 859 microg/L), and molecular analysis of ALAS2 showed a mutation 1731G>A predicting an Arg560His amino acid change [1].
  • We have investigated whether introns 1, 3, and 8, which correspond to DNase I-hypersensitivity sites in the structurally related mouse ALAS2 gene, affect expression of the human ALAS2 promoter in transient expression assays [11].
  • Furthermore, the mapping of the ALAS2 gene to the X chromosome and the observed reduction in ALAS activity in X-linked sideroblastic anemia suggest that this disorder may be due to a mutation in the erythroid-specific gene [12].
  • The ALAS2 gene segregated with the human X chromosome in all 30 hybrid cell lines analyzed and was discordant with all other chromosomes in at least 8 of the 30 hybrids [12].
  • These studies localized the ALAS2 gene to the distal subregion of Xp11.21 in Interval 5 indicating the following gene order: Xpter-OATL2-[L62-3A, Xp11.21; A62-1A-4b, Xp11.21]-(ALAS2, DXS323)-[B13-3, Xp11.21; C9-5, Xp11.21]-(DXS14, DXS429)-DXS422-(DXZ1, Xcen) [2].

Anatomical context of ALAS2

  • A 36-year-old brother was hemizygous for this mutation and expressed the mutated ALAS2 mRNA in his reticulocytes, but showed almost no phenotypic expression [1].
  • Erythroid-specific 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis of erythroid cells [13].
  • Here, we show that treatment of erythroid K562 cells with HDAC inhibitors sodium butyrate or Trichostatin A gave rise to a significant increase in ALAS2 gene transcripts, with a concurrent increase in acetylation level of histone H4 at the ALAS2 gene promoter [13].
  • This suggests that cis-acting elements present in the 5'-flanking region are not responsible for maintenance of transcriptional silencing in non-erythroid cell lines and that tissue-specific regulation of ALAS2 depends on other regions of the gene or on chromatin remodeling [14].
  • Differentiation of embryonic stem cells with a disrupted ALAS2 gene has established that expression of this gene is critical for erythropoiesis and cannot be compensated by expression of the ubiquitous isoform of the enzyme (ALAS1) [15].

Associations of ALAS2 with chemical compounds

  • This is the first study to delimit the cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells [14].
  • R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity [16].
  • The mutation predicted the substitution of leucine for phenylalanine at residue 165 (F165L) in the first highly conserved domain of the ALAS2 catalytic core shared by all species [17].
  • We identified a novel point mutation in the fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn) [18].
  • Consistent with this finding, activity of a bacterially expressed ALAS2 mutant protein harbouring this mutation was 19.5% compared with the normal control, but was increased up to 31.6% by the addition of pyridoxal 5'-phosphate (PLP) in vitro [19].

Physical interactions of ALAS2

  • Histone acetyltransferase p300 bound withALAS2 promoter and overexpression of p300 increased both the promoter reporter expression and endogenous mRNA level of ALAS2 [13].

Regulatory relationships of ALAS2

  • In contrast, iron depletion, known to induce HIF-1 activity but inhibit ALAS2 translation, did not increase ALAS2 promoter activity [5].

Other interactions of ALAS2

  • Using these different cDNAs, the human ALAS housekeeping gene (ALAS1) and the human erythroid-specific (ALAS2) gene have been localized to chromosomes 3p21 and X, respectively, by somatic cell hybrid and in situ hybridization techniques [12].
  • Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43 [20].
  • Both of the GATA-1 sites and all the Sp1 sites at the ALAS2 promoter contributed to the transcription synergistic action with p300 [13].
  • ALAS2 was placed on the multipoint linkage map of the X chromosome in the pericentromeric region with the locus order: pter-(DXS255, TFE3, DXS146)-(DXS14, ALAS2, DXZ1)-AR-(DXS153, DXS159)-qter [21].
  • No recombination between the WWS locus and ALAS2 or with AR (z = 4.890 at theta = 0.0) was found [22].

Analytical, diagnostic and therapeutic context of ALAS2


  1. Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. Cazzola, M., May, A., Bergamaschi, G., Cerani, P., Ferrillo, S., Bishop, D.F. Blood (2002) [Pubmed]
  2. Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations. Cotter, P.D., Willard, H.F., Gorski, J.L., Bishop, D.F. Genomics (1992) [Pubmed]
  3. Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. Cotter, P.D., May, A., Fitzsimons, E.J., Houston, T., Woodcock, B.E., al-Sabah, A.I., Wong, L., Bishop, D.F. J. Clin. Invest. (1995) [Pubmed]
  4. Disparate phenotypic expression of ALAS2 R452H (nt 1407 G --> A) in two brothers, one with severe sideroblastic anemia and iron overload, hepatic cirrhosis, and hepatocellular carcinoma. Barton, J.C., Lee, P.L. Blood Cells Mol. Dis. (2006) [Pubmed]
  5. Hypoxic up-regulation of erythroid 5-aminolevulinate synthase. Hofer, T., Wenger, R.H., Kramer, M.F., Ferreira, G.C., Gassmann, M. Blood (2003) [Pubmed]
  6. Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia. Furuyama, K., Sassa, S. J. Clin. Invest. (2000) [Pubmed]
  7. A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia. Harigae, H., Furuyama, K., Kudo, K., Hayashi, N., Yamamoto, M., Sassa, S., Sasaki, T. Am. J. Hematol. (1999) [Pubmed]
  8. A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. Bekri, S., May, A., Cotter, P.D., Al-Sabah, A.I., Guo, X., Masters, G.S., Bishop, D.F. Blood (2003) [Pubmed]
  9. Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition. Abu-Farha, M., Niles, J., Willmore, W.G. Biochem. Cell Biol. (2005) [Pubmed]
  10. 5-Aminolevulinate synthase expression and hemoglobin synthesis in a human myelogenous leukemia cell line. Nagai, T., Harigae, H., Furuyama, K., Munakata, H., Hayashi, N., Endo, K., Sassa, S., Yamamoto, M. J. Biochem. (1997) [Pubmed]
  11. Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene. Surinya, K.H., Cox, T.C., May, B.K. J. Biol. Chem. (1998) [Pubmed]
  12. Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome. Bishop, D.F., Henderson, A.S., Astrin, K.H. Genomics (1990) [Pubmed]
  13. Histone acetyltransferase p300 regulates the transcription of human erythroid-specific 5-aminolevulinate synthase gene. Han, L., Lu, J., Pan, L., Wang, X., Shao, Y., Han, S., Huang, B. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  14. Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Kramer, M.F., Gunaratne, P., Ferreira, G.C. Gene (2000) [Pubmed]
  15. Regulation of erythroid 5-aminolevulinate synthase expression during erythropoiesis. Sadlon, T.J., Dell'Oso, T., Surinya, K.H., May, B.K. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  16. R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity. Furuyama, K., Uno, R., Urabe, A., Hayashi, N., Fujita, H., Kondo, M., Sassa, S., Yamamoto, M. Br. J. Haematol. (1998) [Pubmed]
  17. X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley. Cotter, P.D., Rucknagel, D.L., Bishop, D.F. Blood (1994) [Pubmed]
  18. Late-onset X-linked sideroblastic anemia following hemodialysis. Furuyama, K., Harigae, H., Kinoshita, C., Shimada, T., Miyaoka, K., Kanda, C., Maruyama, Y., Shibahara, S., Sassa, S. Blood (2003) [Pubmed]
  19. A novel mutation of the erythroid-specific delta-aminolaevulinate synthase gene in a patient with X-linked sideroblastic anaemia. Harigae, H., Furuyama, K., Kimura, A., Neriishi, K., Tahara, N., Kondo, M., Hayashi, N., Yamamoto, M., Sassa, S., Sasaki, T. Br. J. Haematol. (1999) [Pubmed]
  20. Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation. Annunziata, I., Lanzara, C., Conte, I., Zullo, A., Ventruto, V., Rinaldi, M.M., D'Urso, M., Casari, G., Ciccodicola, A., Miano, M.G. Am. J. Med. Genet. A (2003) [Pubmed]
  21. Identification of a highly polymorphic marker within intron 7 of the ALAS2 gene and suggestion of at least two loci for X-linked sideroblastic anemia. Cox, T.C., Kozman, H.M., Raskind, W.H., May, B.K., Mulley, J.C. Hum. Mol. Genet. (1992) [Pubmed]
  22. Localization of the gene for Wieacker-Wolff syndrome in the pericentromeric region of the X chromosome. Kloos, D.U., Jakubiczka, S., Wienker, T., Wolff, G., Wieacker, P. Hum. Genet. (1997) [Pubmed]
  23. Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Cotter, P.D., May, A., Li, L., Al-Sabah, A.I., Fitzsimons, E.J., Cazzola, M., Bishop, D.F. Blood (1999) [Pubmed]
  24. Positional cloning of the zebrafish sauternes gene: a model for congenital sideroblastic anaemia. Brownlie, A., Donovan, A., Pratt, S.J., Paw, B.H., Oates, A.C., Brugnara, C., Witkowska, H.E., Sassa, S., Zon, L.I. Nat. Genet. (1998) [Pubmed]
  25. Cigarette smoking as an etiologic factor in cleft lip and palate. Ericson, A., Källén, B., Westerholm, P. Am. J. Obstet. Gynecol. (1979) [Pubmed]
WikiGenes - Universities