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 a... See more...

Aliases for HAAO Gene

Aliases for HAAO Gene

  • 3-Hydroxyanthranilate 3,4-Dioxygenase 2 3 4 5
  • 3-Hydroxyanthranilic Acid Dioxygenase 3 4
  • 3-Hydroxyanthranilate Oxygenase 3 4
  • EC 1.13.11.6 4 50
  • 3-HAO 3 4
  • H3HAO 3 4
  • HAD 3 4
  • VCRL1 3
  • HAAO 5
  • HAO 3

External Ids for HAAO Gene

Previous GeneCards Identifiers for HAAO Gene

  • GC02M042982
  • GC02M043162
  • GC02M042968
  • GC02M042905
  • GC02M042847
  • GC02M042994
  • GC02M042728

Summaries for HAAO Gene

Entrez Gene Summary for HAAO Gene

  • 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]

GeneCards Summary for HAAO Gene

HAAO (3-Hydroxyanthranilate 3,4-Dioxygenase) is a Protein Coding gene. Diseases associated with HAAO include Vertebral, Cardiac, Renal, And Limb Defects Syndrome 1 and Congenital Vertebral-Cardiac-Renal Anomalies Syndrome. Among its related pathways are superpathway of tryptophan utilization and Tryptophan metabolism. Gene Ontology (GO) annotations related to this gene include iron ion binding and oxygen binding.

UniProtKB/Swiss-Prot Summary for HAAO Gene

  • Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HAAO Gene

Genomics for HAAO Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HAAO Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J042791 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 270.4 +6.9 6902 5.8 SP1 SSRP1 KLF9 POLR2A CEBPA BRCA1 YY1 MXD4 BCL11A ZNF592 HAAO THADA EML4 FTOP1 COX7A2L HSALNG0014492 lnc-MTA3-5 OXER1 MTA3
GH02J042801 Enhancer 0.6 Ensembl dbSUPER 254.7 +0.0 1 1.6 RBM22 NFE2 NFE2L2 ZNF48 ATF4 NFIL3 HAAO OXER1 COX7A2L FTOP1 lnc-HAAO-1 lnc-MTA3-5 MTA3
GH02J042752 Enhancer 0.9 ENCODE CraniofacialAtlas 23.4 +46.5 46525 3.7 BCLAF1 CTCF BHLHE40 EBF1 CBFB MAX SPI1 MYC ZNF24 IKZF1 HAAO KCNG3 MTA3 OXER1 piR-44133-013 HSALNG0014488
GH02J042651 Enhancer 0.8 Ensembl ENCODE 23.9 +148.7 148701 9.8 GABPA MAFF TAL1 ZNF316 MAFK PRDM10 SPI1 POLR2A HDAC2 TCF12 HAAO COX7A2L OXER1 KCNG3 MTA3 HSALNG0014484 HSALNG0014485 lnc-EML4-6 RF00994-476
GH02J042786 Enhancer 0.8 Ensembl CraniofacialAtlas dbSUPER 20.7 +14.7 14671 0.9 MCM3 GATA2 ZSCAN4 RAD21 CHD2 HAAO THADA ZFP36L2 PLEKHH2 FJ601684-245 HSALNG0014492 lnc-MTA3-5 OXER1 MTA3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HAAO on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HAAO

Top Transcription factor binding sites by QIAGEN in the HAAO gene promoter:
  • ATF6
  • E4BP4
  • FOXD3
  • HTF
  • Pax-4a
  • PPAR-gamma1
  • PPAR-gamma2
  • SEF-1 (1)

Genomic Locations for HAAO Gene

Latest Assembly
chr2:42,767,087-42,801,002
(GRCh38/hg38)
Size:
33,916 bases
Orientation:
Minus strand

Previous Assembly
chr2:42,994,229-43,019,723
(GRCh37/hg19 by Entrez Gene)
Size:
25,495 bases
Orientation:
Minus strand

chr2:42,994,229-43,019,733
(GRCh37/hg19 by Ensembl)
Size:
25,505 bases
Orientation:
Minus strand

Genomic View for HAAO Gene

Genes around HAAO on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HAAO Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HAAO Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HAAO Gene

Proteins for HAAO Gene

  • Protein details for HAAO Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P46952-3HAO_HUMAN
    Recommended name:
    3-hydroxyanthranilate 3,4-dioxygenase
    Protein Accession:
    P46952
    Secondary Accessions:
    • A6NE56
    • B4DIN2
    • Q53QZ7
    • Q8N6N9

    Protein attributes for HAAO Gene

    Size:
    286 amino acids
    Molecular mass:
    32556 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Quaternary structure:
    • Monomer.

    Three dimensional structures from OCA and Proteopedia for HAAO Gene

    Alternative splice isoforms for HAAO Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HAAO Gene

Selected DME Specific Peptides for HAAO Gene

P46952:
  • PPVCNKL
  • VPHSPQR
  • RKDYHIEEGEE

Post-translational modifications for HAAO Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for HAAO Gene

Gene Families for HAAO Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for HAAO Gene

GenScript: Design optimal peptide antigens:
  • 3-hydroxyanthranilic acid dioxygenase (3HAO_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P46952

UniProtKB/Swiss-Prot:

3HAO_HUMAN :
  • Belongs to the 3-HAO family.
Family:
  • Belongs to the 3-HAO family.
genes like me logo Genes that share domains with HAAO: view

Function for HAAO Gene

Molecular function for HAAO Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=3-hydroxyanthranilate + O2 = (2Z,4Z)-2-amino-3-carboxymuconate 6-semialdehyde; Xref=Rhea:RHEA:17953, ChEBI:CHEBI:15379, ChEBI:CHEBI:36559, ChEBI:CHEBI:77612; EC=1.13.11.6; Evidence={ECO:0000255|HAMAP-Rule:MF_03019, ECO:0000269|PubMed:28792876, ECO:0000269|PubMed:7514594};.

Enzyme Numbers (IUBMB) for HAAO Gene

Phenotypes From GWAS Catalog for HAAO Gene

Gene Ontology (GO) - Molecular Function for HAAO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000334 3-hydroxyanthranilate 3,4-dioxygenase activity IEA,IDA 7514594
GO:0005506 iron ion binding IEA --
GO:0005515 protein binding IPI 16189514
GO:0008198 ferrous iron binding IEA,IDA 12007609
GO:0009055 electron transfer activity NAS 7514594
genes like me logo Genes that share ontologies with HAAO: view
genes like me logo Genes that share phenotypes with HAAO: view

Human Phenotype Ontology for HAAO Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HAAO Gene

MGI Knock Outs for HAAO:
  • Haao Haao<tm1a(KOMP)Wtsi>
  • Haao Haao<tm2b(KOMP)Mbp>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HAAO

No data available for Transcription Factor Targets and HOMER Transcription for HAAO Gene

Localization for HAAO Gene

Subcellular locations from UniProtKB/Swiss-Prot for HAAO Gene

Cytoplasm, cytosol.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HAAO gene
Compartment Confidence
cytosol 5
cytoskeleton 2
mitochondrion 2
nucleus 2
plasma membrane 1
extracellular 1
peroxisome 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for HAAO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with HAAO: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HAAO Gene

Pathways & Interactions for HAAO Gene

genes like me logo Genes that share pathways with HAAO: view

UniProtKB/Swiss-Prot P46952-3HAO_HUMAN

  • Pathway: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from L-kynurenine: step 3/3.

Gene Ontology (GO) - Biological Process for HAAO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006569 tryptophan catabolic process TAS --
GO:0009435 NAD biosynthetic process IMP 28792876
GO:0010043 response to zinc ion IDA 12007609
GO:0019363 pyridine nucleotide biosynthetic process IEA --
GO:0019805 quinolinate biosynthetic process NAS 7514594
genes like me logo Genes that share ontologies with HAAO: view

No data available for SIGNOR curated interactions for HAAO Gene

Drugs & Compounds for HAAO Gene

(7) Drugs for HAAO Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Oxygen Approved, Vet_approved Pharma 0
3-hydroxyanthranilic acid Experimental Pharma 0
Fe2+ Experimental Pharma 0

(3) Additional Compounds for HAAO Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
2-Amino-3-carboxymuconic acid semialdehyde
  • 2-Amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate
  • 2-Amino-3-(3-oxoprop-1-enyl)-but-2-enedioate
  • 2-Amino-3-carboxymuconate semialdehyde
  • 2-Amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioic acid
  • 2-Amino-3-(3-oxoprop-1-enyl)-but-2-enedioic acid
16597-19-6
genes like me logo Genes that share compounds with HAAO: view

Transcripts for HAAO Gene

mRNA/cDNA for HAAO Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HAAO

Alternative Splicing Database (ASD) splice patterns (SP) for HAAO Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11
SP1: - - -
SP2: - -
SP3: - - - - - -
SP4: -
SP5: -

Relevant External Links for HAAO Gene

GeneLoc Exon Structure for
HAAO

Expression for HAAO Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HAAO Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HAAO Gene

This gene is overexpressed in Liver (x18.2).

Protein differential expression in normal tissues from HIPED for HAAO Gene

This gene is overexpressed in Liver, secretome (27.0) and Liver (10.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HAAO Gene



Protein tissue co-expression partners for HAAO Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HAAO

SOURCE GeneReport for Unigene cluster for HAAO Gene:

Hs.368805

Evidence on tissue expression from TISSUES for HAAO Gene

  • Liver(4.6)
  • Nervous system(4.4)
  • Kidney(2.2)
genes like me logo Genes that share expression patterns with HAAO: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for HAAO Gene

Orthologs for HAAO Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for HAAO Gene

Organism Taxonomy Gene Similarity Type Details
Cow
(Bos Taurus)
Mammalia HAAO 29 30
  • 89.98 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HAAO 29 30
  • 87.52 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Haao 29
  • 86.6 (n)
Mouse
(Mus musculus)
Mammalia Haao 29 16 30
  • 85.33 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HAAO 30
  • 75 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 50 (a)
OneToMany
-- 30
  • 42 (a)
OneToMany
Chicken
(Gallus gallus)
Aves HAAO 29 30
  • 61.03 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HAAO 30
  • 60 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia haao 29
  • 61.96 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC68644 29
Zebrafish
(Danio rerio)
Actinopterygii haao 29 30
  • 57.11 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea haao-1 29 30
  • 48.05 (n)
OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_ACL127W 29
  • 52.16 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes BNA1 29 30 32
  • 46.93 (n)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU03282 29
  • 56.15 (n)
Species where no ortholog for HAAO was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for HAAO Gene

ENSEMBL:
Gene Tree for HAAO (if available)
TreeFam:
Gene Tree for HAAO (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HAAO: view image
Alliance of Genome Resources:
Additional Orthologs for HAAO

Paralogs for HAAO Gene

No data available for Paralogs for HAAO Gene

Variants for HAAO Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HAAO Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs1135401743 Pathogenic: Vertebral, cardiac, renal, and limb defects syndrome 1; Congenital NAD deficiency disorder 42,769,785(-) C/T
NM_012205.3(HAAO):c.558G>A (p.Trp186Ter)
NONSENSE
rs1232096291 Likely Pathogenic: Vertebral, cardiac, renal, and limb defects syndrome 1 42,783,783(-) C/T
NM_012205.3(HAAO):c.243+1G>A
SPLICE_DONOR
rs527656756 Pathogenic: Vertebral, cardiac, renal, and limb defects syndrome 1; Congenital NAD deficiency disorder 42,770,143(-) C/CA
NM_012205.3(HAAO):c.483dup (p.Asp162Ter)
NONSENSE
rs3816182 -- p.Thr42Ser
rs3816183 -- p.Ile37Val

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HAAO Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HAAO Gene

Variant ID Type Subtype PubMed ID
nsv1123321 CNV deletion 24896259
nsv457152 CNV loss 19166990
nsv519877 CNV loss 19592680
nsv581644 CNV loss 21841781
nsv817795 CNV gain 17921354

Variation tolerance for HAAO Gene

Residual Variation Intolerance Score: 90% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.56; 86.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HAAO Gene

Human Gene Mutation Database (HGMD)
HAAO
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HAAO
Leiden Open Variation Database (LOVD)
HAAO

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HAAO Gene

Disorders for HAAO Gene

MalaCards: The human disease database

(3) MalaCards diseases for HAAO Gene - From: OMI, CVR, GTR, ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search HAAO in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

3HAO_HUMAN
  • Vertebral, cardiac, renal, and limb defects syndrome 1 (VCRL1) [MIM:617660]: An autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects. {ECO:0000269 PubMed:28792876}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for HAAO

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HAAO: view

No data available for Genatlas for HAAO Gene

Publications for HAAO Gene

  1. NAD Deficiency, Congenital Malformations, and Niacin Supplementation. (PMID: 28792876) Shi H … Dunwoodie SL (The New England journal of medicine 2017) 2 3 4 72
  2. Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. (PMID: 7514594) Malherbe P … Cesura AM (The Journal of biological chemistry 1994) 2 3 4 22
  3. Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site. (PMID: 28375145) Pidugu LS … Toth EA (Acta crystallographica. Section D, Structural biology 2017) 3 4
  4. Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts. (PMID: 20468071) Dick DM … Bierut L (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 40
  5. Identification of candidate epigenetic biomarkers for ovarian cancer detection. (PMID: 19724865) Huang YW … Lin HJ (Oncology reports 2009) 3 22

Products for HAAO Gene

Sources for HAAO Gene