# ALAS2

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/ALAS2
> Markdown URL: https://mediated.wiki/source/ALAS2.md
> Source: https://en.wikipedia.org/wiki/ALAS2
> Source revision: 1318128830
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

Protein-coding gene in humans

ALAS2 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H7D, 1H7J Identifiers Aliases ALAS2, ALAS-E, ALASE, ANH1, ASB, XLDPP, XLEPP, XLSA, SIDBA1, 5'-aminolevulinate synthase 2 External IDs OMIM: 301300; MGI: 87990; HomoloGene: 17; GeneCards: ALAS2; OMA:ALAS2 - orthologs Gene location (Human) Chr. X chromosome (human)[1] Band Xp11.21 Start 55,009,055 bp[1] End 55,030,977 bp[1] Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X F3|X 68.46 cM Start 149,330,371 bp[2] End 149,353,634 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in trabecular bone bone marrow bone marrow cell blood mononuclear cell monocyte testicle placenta ganglionic eminence spleen Top expressed in blood fetal liver hematopoietic progenitor cell tibiofemoral joint spleen human fetus internal carotid artery left lung external carotid artery right lung right lung lobe More reference expression data BioGPS n/a Gene ontology Molecular function transferase activity glycine binding protein binding catalytic activity pyridoxal phosphate binding acyltransferase activity 5-aminolevulinate synthase activity Cellular component mitochondrial matrix mitochondrion mitochondrial inner membrane Biological process response to hypoxia protoporphyrinogen IX biosynthetic process biosynthesis tetrapyrrole biosynthetic process heme biosynthetic process hemoglobin biosynthetic process erythrocyte differentiation metabolism oxygen homeostasis cellular iron ion homeostasis porphyrin-containing compound metabolic process Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 212 11656 Ensembl ENSG00000158578 ENSMUSG00000025270 UniProt P22557 P08680 RefSeq (mRNA) NM_000032 NM_001037967 NM_001037968 NM_001037969 NM_001102446 NM_009653 RefSeq (protein) NP_000023 NP_001033056 NP_001033057 NP_001095916 NP_033783 Location (UCSC) Chr X: 55.01 – 55.03 Mb Chr X: 149.33 – 149.35 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**Delta-aminolevulinate synthase 2** also known as **ALAS2** is a [protein](/source/Protein) that in humans is encoded by the *ALAS2* gene.[5][6][7] ALAS2 is an [aminolevulinic acid synthase](/source/Aminolevulinic_acid_synthase).

The product of this gene specifies an erythroid-specific [mitochondrially](/source/Mitochondrion) located enzyme. The encoded protein catalyzes the first step in the [heme](/source/Heme) biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive [sideroblastic anemia](/source/Sideroblastic_anemia). [Alternatively spliced](/source/Alternative_splicing) transcript variants encoding different [isoforms](/source/Protein_isoform) have been identified.[7]

Its gene contains an [IRE](/source/Iron_response_element) in its 5'-UTR region on which an [IRP](/source/Iron-responsive_element-binding_protein) binds if the iron level is too low, thus inhibiting its translation.

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000158578](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000158578) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000025270](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000025270) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=212). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=11656). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid2347585_5-0)** Bishop DF, Henderson AS, Astrin KH (Jun 1990). "Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome". *Genomics*. **7** (2): 207–14. [doi](/source/Doi_(identifier)):[10.1016/0888-7543(90)90542-3](https://doi.org/10.1016%2F0888-7543%2890%2990542-3). [PMID](/source/PMID_(identifier)) [2347585](https://pubmed.ncbi.nlm.nih.gov/2347585).

1. **[^](#cite_ref-pmid1577484_6-0)** Cotter PD, Willard HF, Gorski JL, Bishop DF (May 1992). ["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"](https://deepblue.lib.umich.edu/bitstream/2027.42/30074/1/0000444.pdf) (PDF). *Genomics*. **13** (1): 211–2. [doi](/source/Doi_(identifier)):[10.1016/0888-7543(92)90223-F](https://doi.org/10.1016%2F0888-7543%2892%2990223-F). [hdl](/source/Hdl_(identifier)):[2027.42/30074](https://hdl.handle.net/2027.42%2F30074). [PMID](/source/PMID_(identifier)) [1577484](https://pubmed.ncbi.nlm.nih.gov/1577484).

1. ^ [***a***](#cite_ref-entrez_7-0) [***b***](#cite_ref-entrez_7-1) ["Entrez Gene: Delta-aminolevulinate synthase 2"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=212).

## Further reading

- Han L, Zhong Y, Huang B, Han L, Pan L, Xu X, Wang X, Huang B, Lu J (2008). "Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter". *Blood Cells, Molecules & Diseases*. **41** (2): 148–53. [doi](/source/Doi_(identifier)):[10.1016/j.bcmd.2008.04.002](https://doi.org/10.1016%2Fj.bcmd.2008.04.002). [PMID](/source/PMID_(identifier)) [18555711](https://pubmed.ncbi.nlm.nih.gov/18555711).

- Kaneko K, Furuyama K, Aburatani H, Shibahara S (Mar 2009). ["Hypoxia induces erythroid-specific 5-aminolevulinate synthase expression in human erythroid cells through transforming growth factor-beta signaling"](https://doi.org/10.1111%2Fj.1742-4658.2009.06878.x). *The FEBS Journal*. **276** (5): 1370–82. [doi](/source/Doi_(identifier)):[10.1111/j.1742-4658.2009.06878.x](https://doi.org/10.1111%2Fj.1742-4658.2009.06878.x). [PMID](/source/PMID_(identifier)) [19187226](https://pubmed.ncbi.nlm.nih.gov/19187226).

- Cox TC, Sadlon TJ, Schwarz QP, Matthews CS, Wise PD, Cox LL, Bottomley SS, May BK (Feb 2004). "The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis". *The International Journal of Biochemistry & Cell Biology*. **36** (2): 281–95. [doi](/source/Doi_(identifier)):[10.1016/S1357-2725(03)00246-2](https://doi.org/10.1016%2FS1357-2725%2803%2900246-2). [PMID](/source/PMID_(identifier)) [14643893](https://pubmed.ncbi.nlm.nih.gov/14643893).

- Harigae H, Furuyama K, Kudo K, Hayashi N, Yamamoto M, Sassa S, Sasaki T (Oct 1999). ["A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia"](https://doi.org/10.1002%2F%28SICI%291096-8652%28199910%2962%3A2%3C112%3A%3AAID-AJH9%3E3.0.CO%3B2-L). *American Journal of Hematology*. **62** (2): 112–4. [doi](/source/Doi_(identifier)):[10.1002/(SICI)1096-8652(199910)62:2<112::AID-AJH9>3.0.CO;2-L](https://doi.org/10.1002%2F%28SICI%291096-8652%28199910%2962%3A2%3C112%3A%3AAID-AJH9%3E3.0.CO%3B2-L). [PMID](/source/PMID_(identifier)) [10577279](https://pubmed.ncbi.nlm.nih.gov/10577279).

- Hurford MT, Marshall-Taylor C, Vicki SL, Zhou JZ, Silverman LM, Rezuke WN, Altman A, Tsongalis GJ (Jul 2002). "A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia". *Clinica Chimica Acta; International Journal of Clinical Chemistry*. **321** (1–2): 49–53. [doi](/source/Doi_(identifier)):[10.1016/S0009-8981(02)00095-5](https://doi.org/10.1016%2FS0009-8981%2802%2900095-5). [PMID](/source/PMID_(identifier)) [12031592](https://pubmed.ncbi.nlm.nih.gov/12031592).

- Bekri S, May A, Cotter PD, Al-Sabah AI, Guo X, Masters GS, Bishop DF (Jul 2003). ["A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia"](https://doi.org/10.1182%2Fblood-2002-06-1623). *Blood*. **102** (2): 698–704. [doi](/source/Doi_(identifier)):[10.1182/blood-2002-06-1623](https://doi.org/10.1182%2Fblood-2002-06-1623). [PMID](/source/PMID_(identifier)) [12663458](https://pubmed.ncbi.nlm.nih.gov/12663458).

- Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW (Sep 2005). ["Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1224682). *The EMBO Journal*. **24** (18): 3166–77. [doi](/source/Doi_(identifier)):[10.1038/sj.emboj.7600792](https://doi.org/10.1038%2Fsj.emboj.7600792). [PMC](/source/PMC_(identifier)) [1224682](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1224682). [PMID](/source/PMID_(identifier)) [16121195](https://pubmed.ncbi.nlm.nih.gov/16121195).

- Cazzola M, May A, Bergamaschi G, Cerani P, Ferrillo S, Bishop DF (Dec 2002). ["Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation"](https://doi.org/10.1182%2Fblood-2002-03-0685). *Blood*. **100** (12): 4236–8. [doi](/source/Doi_(identifier)):[10.1182/blood-2002-03-0685](https://doi.org/10.1182%2Fblood-2002-03-0685). [PMID](/source/PMID_(identifier)) [12393718](https://pubmed.ncbi.nlm.nih.gov/12393718).

- Sussman NL, Lee PL, Dries AM, Schwartz MR, Barton JC (2008). "Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G". *Acta Haematologica*. **120** (3): 168–73. [doi](/source/Doi_(identifier)):[10.1159/000181183](https://doi.org/10.1159%2F000181183). [PMID](/source/PMID_(identifier)) [19066423](https://pubmed.ncbi.nlm.nih.gov/19066423). [S2CID](/source/S2CID_(identifier)) [10636344](https://api.semanticscholar.org/CorpusID:10636344).

- 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 (Sep 2008). ["C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556430). *American Journal of Human Genetics*. **83** (3): 408–14. [doi](/source/Doi_(identifier)):[10.1016/j.ajhg.2008.08.003](https://doi.org/10.1016%2Fj.ajhg.2008.08.003). [PMC](/source/PMC_(identifier)) [2556430](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556430). [PMID](/source/PMID_(identifier)) [18760763](https://pubmed.ncbi.nlm.nih.gov/18760763).

- Furuyama K, Sassa S (Mar 2000). ["Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC377455). *The Journal of Clinical Investigation*. **105** (6): 757–64. [doi](/source/Doi_(identifier)):[10.1172/JCI6816](https://doi.org/10.1172%2FJCI6816). [PMC](/source/PMC_(identifier)) [377455](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC377455). [PMID](/source/PMID_(identifier)) [10727444](https://pubmed.ncbi.nlm.nih.gov/10727444).

- Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (Sep 2004). ["Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC515316). *Genome Research*. **14** (9): 1711–8. [doi](/source/Doi_(identifier)):[10.1101/gr.2435604](https://doi.org/10.1101%2Fgr.2435604). [PMC](/source/PMC_(identifier)) [515316](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC515316). [PMID](/source/PMID_(identifier)) [15342556](https://pubmed.ncbi.nlm.nih.gov/15342556).

- Lee PL, Barton JC, Rao SV, Acton RT, Adler BK, Beutler E (2006). "Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload". *Blood Cells, Molecules & Diseases*. **36** (2): 292–7. [doi](/source/Doi_(identifier)):[10.1016/j.bcmd.2005.12.004](https://doi.org/10.1016%2Fj.bcmd.2005.12.004). [PMID](/source/PMID_(identifier)) [16446107](https://pubmed.ncbi.nlm.nih.gov/16446107).

- Bergmann AK, Campagna DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ (Feb 2010). ["Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843911). *Pediatric Blood & Cancer*. **54** (2): 273–8. [doi](/source/Doi_(identifier)):[10.1002/pbc.22244](https://doi.org/10.1002%2Fpbc.22244). [PMC](/source/PMC_(identifier)) [2843911](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843911). [PMID](/source/PMID_(identifier)) [19731322](https://pubmed.ncbi.nlm.nih.gov/19731322).

- Rabstein S, Unfried K, Ranft U, Illig T, Kolz M, Mambetova C, Vlad M, Roman C, Weiss T, Becker D, Brüning T, Pesch B (2008). "Lack of association of delta-aminolevulinate dehydratase polymorphisms with blood lead levels and hemoglobin in Romanian women from a lead-contaminated region". *Journal of Toxicology and Environmental Health. Part A*. **71** (11–12): 716–24. [Bibcode](/source/Bibcode_(identifier)):[2008JTEHA..71..716R](https://ui.adsabs.harvard.edu/abs/2008JTEHA..71..716R). [doi](/source/Doi_(identifier)):[10.1080/15287390801985190](https://doi.org/10.1080%2F15287390801985190). [PMID](/source/PMID_(identifier)) [18569569](https://pubmed.ncbi.nlm.nih.gov/18569569). [S2CID](/source/S2CID_(identifier)) [20337081](https://api.semanticscholar.org/CorpusID:20337081).

- Abu-Farha M, Niles J, Willmore WG (Oct 2005). "Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition". *Biochemistry and Cell Biology*. **83** (5): 620–30. [Bibcode](/source/Bibcode_(identifier)):[2005BCB....83..620A](https://ui.adsabs.harvard.edu/abs/2005BCB....83..620A). [doi](/source/Doi_(identifier)):[10.1139/o05-045](https://doi.org/10.1139%2Fo05-045). [PMID](/source/PMID_(identifier)) [16234850](https://pubmed.ncbi.nlm.nih.gov/16234850).

- Nachman MW, D'Agostino SL, Tillquist CR, Mobasher Z, Hammer MF (May 2004). ["Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1470878). *Genetics*. **167** (1): 423–37. [doi](/source/Doi_(identifier)):[10.1534/genetics.167.1.423](https://doi.org/10.1534%2Fgenetics.167.1.423). [PMC](/source/PMC_(identifier)) [1470878](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1470878). [PMID](/source/PMID_(identifier)) [15166166](https://pubmed.ncbi.nlm.nih.gov/15166166).

## External links

- Human [*ALAS2*](https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=ALAS2) genome location and [*ALAS2*](https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=ALAS2) gene details page in the [UCSC Genome Browser](/source/UCSC_Genome_Browser).

- [GeneReviews/NCBI/NIH/UW entry on X-Linked Sideroblastic Anemia and Ataxia](https://www.ncbi.nlm.nih.gov/books/NBK1321/)

*This article incorporates text from the [United States National Library of Medicine](/source/United_States_National_Library_of_Medicine), which is in the [public domain](/source/Public_domain).*

v t e Enzymes involved in the metabolism of heme and porphyrin Porphyrin biosynthesis early mitochondrial: Aminolevulinic acid synthase ALAS1 ALAS2 cytosolic: Porphobilinogen synthase Porphobilinogen deaminase Uroporphyrinogen III synthase Uroporphyrinogen III decarboxylase late mitochondrial: Coproporphyrinogen III oxidase Protoporphyrinogen oxidase Ferrochelatase Heme degradation to bile spleen: Heme oxygenase Biliverdin reductase liver: glucuronosyltransferase UGT1A1

This article on a gene on the human X chromosome and/or its associated protein is a stub. You can help Wikipedia by adding missing information.

- [v](https://en.wikipedia.org/wiki/Template:Gene-X-stub)
- [t](/source/Template_talk%3AGene-X-stub)
- [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Gene-X-stub)

---
Adapted from the Wikipedia article [ALAS2](https://en.wikipedia.org/wiki/ALAS2) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/ALAS2?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.