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    HAAO 3-hydroxyanthranilate 3,4-dioxygenase [ Homo sapiens (human) ]

    Gene ID: 23498, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HAAOprovided by HGNC
    Official Full Name
    3-hydroxyanthranilate 3,4-dioxygenaseprovided by HGNC
    Primary source
    HGNC:HGNC:4796
    See related
    Ensembl:ENSG00000162882 MIM:604521; AllianceGenome:HGNC:4796
    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
    HAO; 3-HAO; VCRL1; h3HAO
    Summary
    3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in liver (RPKM 28.1), kidney (RPKM 12.5) and 13 other tissues See more
    Orthologs
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    Genomic context

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    See HAAO in Genome Data Viewer
    Location:
    2p21
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (42767089..42792583, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (42772378..42797833, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (42994229..43019723, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene metastasis associated 1 family member 3 Neighboring gene RNA, U6 small nuclear 137, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:42983184-42983754 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:42983755-42984326 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:42994558-42995463 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11411 Neighboring gene oxoeicosanoid receptor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11412 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15652 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15653 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11414 Neighboring gene tRNA-Ile (anticodon TAT) 2-1 Neighboring gene FTO pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. Schwarcz R, et al. Proc Natl Acad Sci U S A, 1988 Jun. PMID 2967497, Free PMC Article
    2. Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. Malherbe P, et al. J Biol Chem, 1994 May 13. PMID 7514594
    3. Cloning of human 3-hydroxyanthranilic acid dioxygenase in Escherichia coli: characterisation of the purified enzyme and its in vitro inhibition by Zn2+. Calderone V, et al. Biochim Biophys Acta, 2002 Apr 29. PMID 12007609
    4. Identification of candidate epigenetic biomarkers for ovarian cancer detection. Huang YW, et al. Oncol Rep, 2009 Oct. PMID 19724865, Free PMC Article
    5. Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. Pidugu LS, et al. Acta Crystallogr D Struct Biol, 2017 Apr 1. PMID 28375145, Free PMC Article

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation.
      Title: Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation.
    2. Expression analysis of selected genes involved in tryptophan metabolic pathways in Egyptian children with Autism Spectrum Disorder and learning disabilities.
      Title: Expression analysis of selected genes involved in tryptophan metabolic pathways in Egyptian children with Autism Spectrum Disorder and learning disabilities.
    3. Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion.
      Title: Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion.
    4. Genetic variations of HAAO and IRX6 influence susceptibility to hypospadias in the Japanese population.
      Title: Single Nucleotide Polymorphisms of HAAO and IRX6 Genes as Risk Factors for Hypospadias.
    5. Here, the first crystal structure of human 3-HAO with the native iron bound in its active site is presented, together with an additional structure with zinc (a known inhibitor of human 3-HAO) bound in the active site.
      Title: Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.
    6. Methylation status of CIDEA, HAAO and RXFP3 had significant association with microsatellite instability in endometrial tumors.
      Title: Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas.
    7. GTF2A1 alone, or GTF2A1 plus HAAO are excellent candidate biomarkers for detecting Ovarian cancer
      Title: Identification of candidate epigenetic biomarkers for ovarian cancer detection.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.
    Submit: New GeneRIF Correction

    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
    Vertebral, cardiac, renal, and limb defects syndrome 1
    MedGen: C4540004 OMIM: 617660 GeneReviews: Congenital NAD Deficiency Disorder
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association analyses identify variants in developmental genes associated with hypospadias.
    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)

    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 3-hydroxyanthranilate 3,4-dioxygenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3-hydroxyanthranilate 3,4-dioxygenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables electron transfer activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables ferrous iron binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in 'de novo' NAD biosynthetic process from tryptophan IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in NAD biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in anthranilate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron cellular homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in quinolinate biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in quinolinate biosynthetic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in quinolinate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to cadmium ion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to zinc ion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tryptophan catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    3-hydroxyanthranilate 3,4-dioxygenase
    Names
    3-hydroxyanthranilate oxygenase
    3-hydroxyanthranilic acid dioxygenase
    HAD
    NP_036337.2
    XP_011531031.1
    XP_011531032.1
    XP_054197187.1
    XP_054197188.1

    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_012205.3 → NP_036337.2  3-hydroxyanthranilate 3,4-dioxygenase

      See identical proteins and their annotated locations for NP_036337.2

      Status: REVIEWED

      Source sequence(s)
      BI602406, CB850657, Z29481
      Consensus CDS
      CCDS33187.1
      UniProtKB/Swiss-Prot
      A6NE56, B4DIN2, P46952, Q53QZ7, Q8N6N9
      Related
      ENSP00000294973.6, ENST00000294973.11
      Conserved Domains (1) summary
      pfam06052
      Location:2 → 149
      3-HAO; 3-hydroxyanthranilic acid dioxygenase

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      42767089..42792583 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011532729.4 → XP_011531031.1  3-hydroxyanthranilate 3,4-dioxygenase isoform X1

      Conserved Domains (1) summary
      cl21464
      Location:2 → 122
      cupin_like; Conserved domain found in cupin and related proteins

    2. XM_011532730.4 → XP_011531032.1  3-hydroxyanthranilate 3,4-dioxygenase isoform X2

      Conserved Domains (1) summary
      cl21464
      Location:1 → 115
      cupin_like; Conserved domain found in cupin and related proteins

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      42772378..42797833 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341212.1 → XP_054197187.1  3-hydroxyanthranilate 3,4-dioxygenase isoform X1

    2. XM_054341213.1 → XP_054197188.1  3-hydroxyanthranilate 3,4-dioxygenase isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P46952.2 GenPept UniProtKB/Swiss-Prot:P46952

    Gene LinkOut

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

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