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    ALAS2 5'-aminolevulinate synthase 2 [ Homo sapiens (human) ]

    Gene ID: 212, updated on 27-Nov-2024

    Summary

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    Official Symbol
    ALAS2provided by HGNC
    Official Full Name
    5'-aminolevulinate synthase 2provided by HGNC
    Primary source
    HGNC:HGNC:397
    See related
    Ensembl:ENSG00000158578 MIM:301300; AllianceGenome:HGNC:397
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ASB; ANH1; XLSA; ALASE; XLDPP; XLEPP; ALAS-E; SIDBA1
    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]
    Expression
    Restricted expression toward bone marrow (RPKM 181.6) See more
    Orthologs
    mouse all
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    Genomic context

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    See ALAS2 in Genome Data Viewer
    Location:
    Xp11.21
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (55009055..55030977, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (54302181..54324103, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (55035488..55057410, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chrX:54962395-54962556 Neighboring gene small nucleolar RNA, H/ACA box 11G Neighboring gene trophinin Neighboring gene 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:54977103-54977603 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20865 Neighboring gene Sharpr-MPRA regulatory regions 2439 and 5762 Neighboring gene ALAS2 intronic erythroid enhancer Neighboring gene apurinic/apyrimidinic endodeoxyribonuclease 2 Neighboring gene ALAS2 intron 1 and 3 erythroid regulatory elements Neighboring gene PAGE family member 2B Neighboring gene HDGFL3 pseudogene 1 Neighboring gene PAGE family member 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. X-Linked Protoporphyria. Adam MP, et al. , 1993. PMID 23409301
    2. The unfolding pathways of the native and molten globule states of 5-aminolevulinate synthase. Stojanovski BM, et al. Biochem Biophys Res Commun, 2016 Nov 18. PMID 27751851
    3. Human Erythroid 5-Aminolevulinate Synthase Mutations Associated with X-Linked Protoporphyria Disrupt the Conformational Equilibrium and Enhance Product Release. Fratz EJ, et al. Biochemistry, 2015 Sep 15. PMID 26300302, Free PMC Article
    4. R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity. Furuyama K, et al. Br J Haematol, 1998 Dec. PMID 9858242
    5. X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation. Sankaran VG, et al. J Clin Invest, 2015 Apr. PMID 25705881, Free PMC Article

    See all (76) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Key Genes FECH and ALAS2 under Acute High-Altitude Exposure: A Gene Expression and Network Analysis Based on Expression Profile Data.
      Title: Key Genes FECH and ALAS2 under Acute High-Altitude Exposure: A Gene Expression and Network Analysis Based on Expression Profile Data.
    2. Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.
      Title: Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.
    3. A synonymous coding variant that alters ALAS2 splicing and causes X-linked sideroblastic anemia.
      Title: A synonymous coding variant that alters ALAS2 splicing and causes X-linked sideroblastic anemia.
    4. 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.
      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.
    5. A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria.
      Title: A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria.
    6. Novel mutations in the ALAS2 gene from patients with X-linked sideroblastic anemia.
      Title: Novel mutations in the ALAS2 gene from patients with X-linked sideroblastic anemia.
    7. [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L].
      Title: [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L].
    8. Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release.
      Title: Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release.
    9. In erythropoietic protoporphyria, ALAS2 mRNA was increased both in absolute terms and in relation to deficiency in ferrochelatase mRNA as shown in this study.
      Title: Delta-aminolevulinic acid synthase 2 expression in combination with iron as modifiers of disease severity in erythropoietic protoporphyria.
    10. A novel mutation, c.1108G > A (p.A370T, NM_000032), was found in the ALAS2 gene located in exon 8. A mother with X-linked sideroblastic anemia and her so-far asymptomatic daughter were heterozygous for this mutation.
      Title: Identification of a novel heterozygous ALAS2 mutation in a young Chinese female with X-linked sideroblastic anemia.
    Submit: New GeneRIF Correction See all GeneRIFs (47)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    X-linked erythropoietic protoporphyria
    MedGen: C2677889 OMIM: 300752 GeneReviews: X-Linked Protoporphyria
    		Compare labs
    X-linked sideroblastic anemia 1
    MedGen: C4551511 OMIM: 300751 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ93603

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 5-aminolevulinate synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 5-aminolevulinate synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 5-aminolevulinate synthase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables pyridoxal phosphate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in erythrocyte development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in erythrocyte differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in erythrocyte differentiation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in heme biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in heme biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in heme biosynthetic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in hemoglobin biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in hemoglobin biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in intracellular iron ion homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in intracellular oxygen homeostasis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in protoporphyrinogen IX biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to hypoxia IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    5-aminolevulinate synthase, erythroid-specific, mitochondrial
    Names
    5-aminolevulinic acid synthase 2
    aminolevulinate, delta-, synthase 2
    delta-ALA synthase 2
    delta-ALA synthetase
    delta-aminolevulinate synthase 2
    erythroid-specific delta-aminolevulinate synthase
    NP_000023.2
    NP_001033056.1
    NP_001033057.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008983.1 RefSeqGene

      Range
      5088..27010
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1163

    mRNA and Protein(s)

    1. NM_000032.5 → NP_000023.2  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform a precursor

      See identical proteins and their annotated locations for NP_000023.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AK313118, BQ182291
      Consensus CDS
      CCDS14366.1
      UniProtKB/Swiss-Prot
      A8K3F0, A8K6C4, P22557, Q13735, Q5JZF5, Q8N6H3
      Related
      ENSP00000497236.1, ENST00000650242.1
      Conserved Domains (3) summary
      COG0156
      Location:143 → 534
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      TIGR01821
      Location:143 → 548
      5aminolev_synth; 5-aminolevulinic acid synthase
      pfam09029
      Location:5 → 100
      Preseq_ALAS; 5-aminolevulinate synthase presequence

    2. NM_001037967.4 → NP_001033056.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform b precursor

      See identical proteins and their annotated locations for NP_001033056.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (b) that is shorter than isoform a.
      Source sequence(s)
      AK291589, BQ182291
      Consensus CDS
      CCDS35303.1
      UniProtKB/Swiss-Prot
      P22557
      Related
      ENSP00000337131.4, ENST00000335854.8
      Conserved Domains (3) summary
      COG0156
      Location:106 → 497
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      TIGR01821
      Location:106 → 511
      5aminolev_synth; 5-aminolevulinic acid synthase
      pfam09029
      Location:5 → 100
      Preseq_ALAS; 5-aminolevulinate synthase presequence

    3. NM_001037968.4 → NP_001033057.1  5-aminolevulinate synthase, erythroid-specific, mitochondrial isoform c precursor

      See identical proteins and their annotated locations for NP_001033057.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, has an additional 5' exon resulting in an alternate start codon, and lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The resulting isoform (c) is shorter but has a longer and distinct N-terminus, compared to isoform a.
      Source sequence(s)
      AL020991, BP233279, BQ182291
      Consensus CDS
      CCDS43960.1
      UniProtKB/Swiss-Prot
      P22557
      Related
      ENSP00000379501.3, ENST00000396198.7
      Conserved Domains (3) summary
      COG0156
      Location:130 → 521
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      TIGR01821
      Location:130 → 535
      5aminolev_synth; 5-aminolevulinic acid synthase
      pfam09029
      Location:29 → 124
      Preseq_ALAS; 5-aminolevulinate synthase presequence

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      55009055..55030977 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      54302181..54324103 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001037969.2: Suppressed sequence

      Description
      NM_001037969.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P22557.2 GenPept UniProtKB/Swiss-Prot:P22557

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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