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    ALAS1 5'-aminolevulinate synthase 1 [ Homo sapiens (human) ]

    Gene ID: 211, updated on 27-Nov-2024

    Summary

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    Official Symbol
    ALAS1provided by HGNC
    Official Full Name
    5'-aminolevulinate synthase 1provided by HGNC
    Primary source
    HGNC:HGNC:396
    See related
    Ensembl:ENSG00000023330 MIM:125290; AllianceGenome:HGNC:396
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ALAS; MIG4; ALAS3; ALASH; ALAS-H
    Summary
    This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]
    Expression
    Biased expression in adrenal (RPKM 297.6), liver (RPKM 180.6) and 9 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ALAS1 in Genome Data Viewer
    Location:
    3p21.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (52198083..52214327)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (52230963..52247212)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52232099..52248343)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52112399-52113318 Neighboring gene POC1 centriolar protein A Neighboring gene Sharpr-MPRA regulatory region 14635 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19927 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52187832-52188809 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52188810-52189786 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52218535-52219370 Neighboring gene Sharpr-MPRA regulatory region 13023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19928 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19929 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14431 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14432 Neighboring gene ALDOA pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 10522 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19930 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52259793-52260294 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52260295-52260794 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14433 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:52270765-52271306 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:52271307-52271849 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14434 Neighboring gene toll like receptor 9 Neighboring gene twinfilin actin binding protein 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. Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. May BK, et al. Mol Biol Med, 1990 Oct. PMID 2095458
    2. Novel Mechanisms for Heme-dependent Degradation of ALAS1 Protein as a Component of Negative Feedback Regulation of Heme Biosynthesis. Kubota Y, et al. J Biol Chem, 2016 Sep 23. PMID 27496948, Free PMC Article
    3. Onset of X-linked sideroblastic anemia in the fourth decade. Cortesão E, et al. Haematologica, 2004 Oct. PMID 15477213
    4. Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells. Ju Y, et al. Endocrinology, 2012 Nov. PMID 23024262
    5. Multiple mechanisms for hereditary sideroblastic anemia. Furuyama K, et al. Cell Mol Biol (Noisy-le-grand), 2002 Feb. PMID 11929048

    See all (76) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX.
      Title: Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX.
    2. 5-Aminolevulinate dehydratase porphyria: Update on hepatic 5-aminolevulinic acid synthase induction and long-term response to hemin.
      Title: 5-Aminolevulinate dehydratase porphyria: Update on hepatic 5-aminolevulinic acid synthase induction and long-term response to hemin.
    3. Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro.
      Title: Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro.
    4. The mutation in CLPX inactivates its ATPase activity, resulting in coassembly of mutant and WT protomers to form an enzyme with reduced activity. The presence of low-activity CLPX increases the posttranslational stability of ALAS, causing increased ALAS protein and ALA levels, leading to abnormal accumulation of PPIX.
      Title: Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria.
    5. the heme-binding site in the N-terminal region of the mature ALAS1 protein is also necessary for the heme-dependent oxidation of ALAS1.
      Title: Novel Mechanisms for Heme-dependent Degradation of ALAS1 Protein as a Component of Negative Feedback Regulation of Heme Biosynthesis.
    6. ALAS1 mRNA and activity were elevated approximately ~3- and 5-fold, and HMB synthase activity was approximately half-normal (~42%)
      Title: Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver.
    7. The -853T variant functions as an enhancer in the presence of estrogen and speculates that the -1253A variant reduces transcription activity.
      Title: Functional analysis of the 5' regulatory region of the 5-aminolevulinate synthase (ALAS1) gene in response to estrogen.
    8. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.
      Title: Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.
    9. Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.
      Title: Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.
    10. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
    EBI GWAS Catalog
    Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of aminolevulinate, delta-, synthase 1 (ALAS1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    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 identical protein binding IPI
    Inferred from Physical Interaction
    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 heme A biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in heme B biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in heme O biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in heme biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in hemoglobin biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protoporphyrinogen IX biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to bile acid IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrial inner membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    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
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    5-aminolevulinate synthase, non-specific, mitochondrial
    Names
    5-aminolevulinate synthase, nonspecific, mitochondrial
    5-aminolevulinic acid synthase 1
    aminolevulinate, delta-, synthase 1
    delta-ALA synthase 1
    delta-aminolevulinate synthase 1
    migration-inducing protein 4
    NP_000679.1
    NP_001291372.1
    NP_001291373.1
    NP_954635.1
    XP_011531779.1
    XP_011531780.1
    XP_016861362.1
    XP_054201640.1
    XP_054201641.1
    XP_054201642.1

    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.

    mRNA and Protein(s)

    1. NM_000688.6 → NP_000679.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_000679.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, and 3 encode the same protein.
      Source sequence(s)
      AI868691, AU279391, BC011798, CD014147, X56351
      Consensus CDS
      CCDS2847.1
      UniProtKB/Swiss-Prot
      P13196
      UniProtKB/TrEMBL
      A0A024R353, B4DVA0, Q5JAM2
      Related
      ENSP00000418779.1, ENST00000484952.6
      Conserved Domains (2) summary
      pfam09029
      Location:2 → 137
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:197 → 602
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    2. NM_001304443.1 → NP_001291372.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_001291372.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) lacks an alternate exon and uses an alternate splice site in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AB063322, AK300993, BM546974, DA691060, Y00451
      Consensus CDS
      CCDS2847.1
      UniProtKB/Swiss-Prot
      P13196
      UniProtKB/TrEMBL
      A0A024R353, B4DVA0, Q5JAM2
      Related
      ENSP00000309259.2, ENST00000310271.6
      Conserved Domains (2) summary
      pfam09029
      Location:2 → 137
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:197 → 602
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    3. NM_001304444.1 → NP_001291373.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) uses an alternate splice site in its 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is longer than isoform 1.
      Source sequence(s)
      AB063322, AK300993, BM546974, DA691060
      UniProtKB/TrEMBL
      B4DVA0
      Conserved Domains (3) summary
      COG0156
      Location:214 → 605
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      pfam09029
      Location:19 → 154
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:214 → 619
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    4. NM_199166.2 → NP_954635.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_954635.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AI868691, BM546974, BU173391, X56351
      Consensus CDS
      CCDS2847.1
      UniProtKB/Swiss-Prot
      P13196
      UniProtKB/TrEMBL
      A0A024R353, B4DVA0, Q5JAM2
      Related
      ENSP00000417719.1, ENST00000469224.5
      Conserved Domains (2) summary
      pfam09029
      Location:2 → 137
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:197 → 602
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      52198083..52214327
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011533478.3 → XP_011531780.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B4DVA0
      Conserved Domains (3) summary
      COG0156
      Location:214 → 550
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      pfam09029
      Location:19 → 154
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:214 → 564
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    2. XM_017005873.2 → XP_016861362.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform X3

      UniProtKB/TrEMBL
      B4DVA0
      Conserved Domains (2) summary
      pfam09029
      Location:2 → 137
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:197 → 547
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    3. XM_011533477.3 → XP_011531779.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform X1

      UniProtKB/TrEMBL
      B4DVA0
      Conserved Domains (3) summary
      COG0156
      Location:214 → 604
      BioF; 7-keto-8-aminopelargonate synthetase or related enzyme [Coenzyme transport and metabolism]
      pfam09029
      Location:19 → 154
      Preseq_ALAS; 5-aminolevulinate synthase presequence
      cl18945
      Location:214 → 603
      AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      52230963..52247212
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054345666.1 → XP_054201641.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform X2

    2. XM_054345667.1 → XP_054201642.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform X3

    3. XM_054345665.1 → XP_054201640.1  5-aminolevulinate synthase, non-specific, mitochondrial isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P13196.2 GenPept UniProtKB/Swiss-Prot:P13196

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