LOCUS       NM_000032               1940 bp    mRNA    linear   PRI 15-OCT-2024
DEFINITION  Homo sapiens 5'-aminolevulinate synthase 2 (ALAS2), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_000032
VERSION     NM_000032.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1940)
  AUTHORS   Zhao,Y., Zhu,L., Shi,D., Gao,J. and Fan,M.
  TITLE     Key Genes FECH and ALAS2 under Acute High-Altitude Exposure: A Gene
            Expression and Network Analysis Based on Expression Profile Data
  JOURNAL   Genes (Basel) 15 (8), 1075 (2024)
   PUBMED   39202434
  REMARK    GeneRIF: Key Genes FECH and ALAS2 under Acute High-Altitude
            Exposure: A Gene Expression and Network Analysis Based on
            Expression Profile Data.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1940)
  AUTHORS   Ono,K., Fujiwara,T., Saito,K., Nishizawa,H., Takahashi,N.,
            Suzuki,C., Ochi,T., Kato,H., Ishii,Y., Onodera,K., Ichikawa,S.,
            Fukuhara,N., Onishi,Y., Yokoyama,H., Yamada,R., Nakamura,Y.,
            Igarashi,K. and Harigae,H.
  TITLE     Congenital sideroblastic anemia model due to ALAS2 mutation is
            susceptible to ferroptosis
  JOURNAL   Sci Rep 12 (1), 9024 (2022)
   PUBMED   35637209
  REMARK    GeneRIF: Congenital sideroblastic anemia model due to ALAS2
            mutation is susceptible to ferroptosis.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1940)
  AUTHORS   de Gennes,C., Lamoril,J., Borgel,A., Boi,C., Yao,R., Boileau,C. and
            Tchernitchko,D.
  TITLE     Severe iron overload in a woman with homeostatic iron regulator
            (HFE) and a novel 5'-aminolevulinate synthase 2 (ALAS2) mutations:
            interactions of multiple genetic determinants
  JOURNAL   Br J Haematol 196 (2), e17-e20 (2022)
   PUBMED   34490613
  REMARK    GeneRIF: Severe iron overload in a woman with homeostatic iron
            regulator (HFE) and a novel 5'-aminolevulinate synthase 2 (ALAS2)
            mutations: interactions of multiple genetic determinants.
REFERENCE   4  (bases 1 to 1940)
  AUTHORS   Oakley,J.H., Campagna,D.R., Sun,L., Rockowitz,S., Sliz,P.,
            Boudreaux,J., Woods,G. and Fleming,M.D.
  TITLE     A synonymous coding variant that alters ALAS2 splicing and causes
            X-linked sideroblastic anemia
  JOURNAL   Pediatr Blood Cancer 69 (1), e29309 (2022)
   PUBMED   34411431
  REMARK    GeneRIF: A synonymous coding variant that alters ALAS2 splicing and
            causes X-linked sideroblastic anemia.
REFERENCE   5  (bases 1 to 1940)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   6  (bases 1 to 1940)
  AUTHORS   Balwani,M. and Desnick,R.
  CONSRTM   Porphyrias Consortium of the NIH-Sponsored Rare Diseases Clinical
            Research Network
  TITLE     X-Linked Protoporphyria
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   23409301
REFERENCE   7  (bases 1 to 1940)
  AUTHORS   Cotter,P.D., Baumann,M. and Bishop,D.F.
  TITLE     Enzymatic defect in 'X-linked' sideroblastic anemia: molecular
            evidence for erythroid delta-aminolevulinate synthase deficiency
  JOURNAL   Proc Natl Acad Sci U S A 89 (9), 4028-4032 (1992)
   PUBMED   1570328
REFERENCE   8  (bases 1 to 1940)
  AUTHORS   Cotter,P.D., Willard,H.F., Gorski,J.L. and Bishop,D.F.
  TITLE     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
  JOURNAL   Genomics 13 (1), 211-212 (1992)
   PUBMED   1577484
REFERENCE   9  (bases 1 to 1940)
  AUTHORS   Gardner,L.C., Smith,S.J. and Cox,T.M.
  TITLE     Biosynthesis of delta-aminolevulinic acid and the regulation of
            heme formation by immature erythroid cells in man
  JOURNAL   J Biol Chem 266 (32), 22010-22018 (1991)
   PUBMED   1939222
REFERENCE   10 (bases 1 to 1940)
  AUTHORS   Cox,T.C., Bawden,M.J., Martin,A. and May,B.K.
  TITLE     Human erythroid 5-aminolevulinate synthase: promoter analysis and
            identification of an iron-responsive element in the mRNA
  JOURNAL   EMBO J 10 (7), 1891-1902 (1991)
   PUBMED   2050125
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK313118.1 and BQ182291.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 8, 2018 this sequence version replaced NM_000032.4.
            
            Summary: The product of this gene specifies an erythroid-specific
            mitochondrially located enzyme. The encoded protein catalyzes the
            first step in the heme biosynthetic pathway. Defects in this gene
            cause X-linked pyridoxine-responsive sideroblastic anemia.
            Alternatively spliced transcript variants encoding different
            isoforms have been identified. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (a).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X60364.1, SRR3476690.828307.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1966682,
                                           SAMEA1968540 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000650242.1/
                                                  ENSP00000497236.1
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1815              AK313118.1         88-1902
            1816-1940           BQ182291.1         18-142              c
FEATURES             Location/Qualifiers
     source          1..1940
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp11.21"
     gene            1..1940
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /note="5'-aminolevulinate synthase 2"
                     /db_xref="GeneID:212"
                     /db_xref="HGNC:HGNC:397"
                     /db_xref="MIM:301300"
     exon            1..36
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            37..232
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     CDS             52..1815
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /EC_number="2.3.1.37"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; delta-ALA synthetase; 5-aminolevulinate
                     synthase, erythroid-specific, mitochondrial; delta-ALA
                     synthase 2; 5-aminolevulinic acid synthase 2;
                     delta-aminolevulinate synthase 2; aminolevulinate, delta-,
                     synthase 2; erythroid-specific delta-aminolevulinate
                     synthase"
                     /codon_start=1
                     /product="5-aminolevulinate synthase, erythroid-specific,
                     mitochondrial isoform a precursor"
                     /protein_id="NP_000023.2"
                     /db_xref="CCDS:CCDS14366.1"
                     /db_xref="GeneID:212"
                     /db_xref="HGNC:HGNC:397"
                     /db_xref="MIM:301300"
                     /translation="MVTAAMLLQCCPVLARGPTSLLGKVVKTHQFLFGIGRCPILATQ
                     GPNCSQIHLKATKAGGDSPSWAKGHCPFMLSELQDGKSKIVQKAAPEVQEDVKAFKTD
                     LPSSLVSVSLRKPFSGPQEQEQISGKVTHLIQNNMPGNYVFSYDQFFRDKIMEKKQDH
                     TYRVFKTVNRWADAYPFAQHFSEASVASKDVSVWCSNDYLGMSRHPQVLQATQETLQR
                     HGAGAGGTRNISGTSKFHVELEQELAELHQKDSALLFSSCFVANDSTLFTLAKILPGC
                     EIYSDAGNHASMIQGIRNSGAAKFVFRHNDPDHLKKLLEKSNPKIPKIVAFETVHSMD
                     GAICPLEELCDVSHQYGALTFVDEVHAVGLYGSRGAGIGERDGIMHKIDIISGTLGKA
                     FGCVGGYIASTRDLVDMVRSYAAGFIFTTSLPPMVLSGALESVRLLKGEEGQALRRAH
                     QRNVKHMRQLLMDRGLPVIPCPSHIIPIRVGNAALNSKLCDLLLSKHGIYVQAINYPT
                     VPRGEELLRLAPSPHHSPQMMEDFVEKLLLAWTAVGLPLQDVSVAACNFCRRPVHFEL
                     MSEWERSYFGNMGPQYVTTYA"
     exon            233..355
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            356..466
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            467..689
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            690..874
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            875..1054
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            1055..1219
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..1488
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            1489..1651
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     exon            1652..1940
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1920..1925
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /note="hexamer: AATAAA"
     polyA_site      1940
                     /gene="ALAS2"
                     /gene_synonym="ALAS-E; ALASE; ANH1; ASB; SIDBA1; XLDPP;
                     XLEPP; XLSA"
                     /note="major polyA site"
ORIGIN      
        1 acctgtcatt cgttcgtcct cagtgcaggg caacaggact ttaggttcaa gatggtgact
       61 gcagccatgc tgctacagtg ctgcccagtg cttgcccggg gccccacaag cctcctaggc
      121 aaggtggtta agactcacca gttcctgttt ggtattggac gctgtcccat cctggctacc
      181 caaggaccaa actgttctca aatccacctt aaggcaacaa aggctggagg agattctcca
      241 tcttgggcga agggccactg tcccttcatg ctgtcggaac tccaggatgg gaagagcaag
      301 attgtgcaga aggcagcccc agaagtccag gaagatgtga aggctttcaa gacagatctg
      361 cctagctccc tggtctcagt cagcctaagg aagccatttt ccggtcccca ggagcaggag
      421 cagatctctg ggaaggtcac acacctgatt cagaacaata tgcctggaaa ctatgtcttc
      481 agttatgacc agtttttcag ggacaagatc atggagaaga aacaggatca cacctaccgt
      541 gtgttcaaga ctgtgaaccg ctgggctgat gcatatccct ttgcccaaca tttctctgag
      601 gcatctgtgg cctcaaagga tgtgtccgtc tggtgtagta atgattacct gggcatgagc
      661 cgacaccctc aggtcttgca agccacacag gagaccctgc agcgtcatgg tgctggagct
      721 ggtggcaccc gcaacatctc aggcaccagt aagtttcatg tggagcttga gcaggagctg
      781 gctgagctgc accagaagga ctcagccctg ctcttctcct cctgctttgt tgccaatgac
      841 tctactctct tcaccttggc caagatcctg ccagggtgcg agatttactc agacgcaggc
      901 aaccatgctt ccatgatcca aggtatccgt aacagtggag cagccaagtt tgtcttcagg
      961 cacaatgacc ctgaccacct aaagaaactt ctagagaagt ctaaccctaa gatacccaaa
     1021 attgtggcct ttgagactgt ccactccatg gatggtgcca tctgtcccct cgaggagttg
     1081 tgtgatgtgt cccaccagta tggggccctg accttcgtgg atgaggtcca tgctgtagga
     1141 ctgtatgggt cccggggcgc tgggattggg gagcgtgatg gaattatgca taagattgac
     1201 atcatctctg gaactcttgg caaggccttt ggctgtgtgg gcggctacat tgccagcacc
     1261 cgtgacttgg tggacatggt gcgctcctat gctgcaggct tcatctttac cacttctctg
     1321 ccccccatgg tgctctctgg agctctagaa tctgtgcggc tgctcaaggg agaggagggc
     1381 caagccctga ggcgagccca ccagcgcaat gtcaagcaca tgcgccagct actcatggac
     1441 aggggccttc ctgtcatccc ctgccccagc cacatcatcc ccatccgggt gggcaatgca
     1501 gcactcaaca gcaagctctg tgatctcctg ctctccaagc atggcatcta tgtgcaggcc
     1561 atcaactacc caactgtccc ccggggtgaa gagctcctgc gcttggcacc ctccccccac
     1621 cacagccctc agatgatgga agattttgtg gagaagctgc tgctggcttg gactgcggtg
     1681 gggctgcccc tccaggatgt gtctgtggct gcctgcaatt tctgtcgccg tcctgtacac
     1741 tttgagctca tgagtgagtg ggaacgttcc tacttcggga acatggggcc ccagtatgtc
     1801 accacctatg cctgagaagc cagctgccta ggattcacac cccacctgcg cttcacttgg
     1861 gtccaggcct actcctgtct tctgctttgt tgtgtgcctc tagctgaatt gagcctaaaa
     1921 ataaagcaca aaccacagca
//
