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

Gene ID: 211, updated on 2-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
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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 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)

Genotypes

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

Gene LinkOut

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