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

Gene ID: 212, updated on 5-Mar-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (55009055..55030977, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (54302181..54324103, complement)
105.20220307 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. Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis. Ono K, et al. Sci Rep, 2022 May 30. PMID 35637209, Free PMC Article
  2. A synonymous coding variant that alters ALAS2 splicing and causes X-linked sideroblastic anemia. Oakley JH, et al. Pediatr Blood Cancer, 2022 Jan. PMID 34411431
  3. A mutation in the iron-responsive element of ALAS2 is a modifier of disease severity in a patient suffering from CLPX associated erythropoietic protoporphyria. Ducamp S, et al. Haematologica, 2021 Jul 1. PMID 33596641, Free PMC Article
  4. Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release. Bailey HJ, et al. Nat Commun, 2020 Jun 4. PMID 32499479, Free PMC Article
  5. Novel mutations in the ALAS2 gene from patients with X-linked sideroblastic anemia. Li J, et al. Int J Lab Hematol, 2020 Aug. PMID 32297424

See all (73) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. [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].
  7. 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.
  8. 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.
  9. 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.
  10. Patients with porphyrias should always be assessed for the presence of the ALAS2 gain-of-function modifier variants identified here. A key region of the ALAS2 carboxyterminal region is identified by the truncation mutations, and the correlation of increased thermolability with activity suggests that increased molecular flexibility/active site openness is the mechanism of enhanced function of mutations in this region.
    Title: Molecular expression, characterization and mechanism of ALAS2 gain-of-function mutants.
Submit: New GeneRIF Correction See all GeneRIFs (46)

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)

Genotypes

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
  
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_2023_10

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

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