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Aliases for HPD Gene

Aliases for HPD Gene

  • 4-Hydroxyphenylpyruvate Dioxygenase 2 3 5
  • 4-Hydroxyphenylpyruvic Acid Oxidase 3 4
  • Glyoxalase Domain Containing 3 2 3
  • EC 4 63
  • HPPDASE 3 4
  • 4HPPD 3 4
  • PPD 3 4
  • 4-HPPD 3
  • GLOD3 3

External Ids for HPD Gene

Previous HGNC Symbols for HPD Gene

  • PPD

Previous GeneCards Identifiers for HPD Gene

  • GC12M121132
  • GC12P121808
  • GC12M122046
  • GC12M120675
  • GC12M120740
  • GC12M122277
  • GC12M119289

Summaries for HPD Gene

Entrez Gene Summary for HPD Gene

  • The protein encoded by this gene is an enzyme in the catabolic pathway of tyrosine. The encoded protein catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. Defects in this gene are a cause of tyrosinemia type 3 (TYRO3) and hawkinsinuria (HAWK). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

GeneCards Summary for HPD Gene

HPD (4-Hydroxyphenylpyruvate Dioxygenase) is a Protein Coding gene. Diseases associated with HPD include Tyrosinemia, Type Iii and Hawkinsinuria. Among its related pathways are Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism and Ubiquinol biosynthesis. GO annotations related to this gene include oxidoreductase activity, acting on single donors with incorporation of molecular oxygen and 4-hydroxyphenylpyruvate dioxygenase activity. An important paralog of this gene is HPDL.

UniProtKB/Swiss-Prot for HPD Gene

  • Key enzyme in the degradation of tyrosine.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HPD Gene

Genomics for HPD Gene

Regulatory Elements for HPD Gene

Enhancers for HPD Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HPD on UCSC Golden Path with GeneCards custom track

Promoters for HPD Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HPD on UCSC Golden Path with GeneCards custom track

Genomic Location for HPD Gene

121,839,527 bp from pter
121,888,611 bp from pter
49,085 bases
Minus strand

Genomic View for HPD Gene

Genes around HPD on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HPD Gene

Proteins for HPD Gene

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

    Protein Symbol:
    Recommended name:
    4-hydroxyphenylpyruvate dioxygenase
    Protein Accession:
    Secondary Accessions:
    • A8K461
    • B3KQ63
    • Q13234

    Protein attributes for HPD Gene

    393 amino acids
    Molecular mass:
    44934 Da
    Name=Fe cation; Xref=ChEBI:CHEBI:24875;
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for HPD Gene

    Alternative splice isoforms for HPD Gene


neXtProt entry for HPD Gene

Proteomics data for HPD Gene at MOPED

Post-translational modifications for HPD Gene

  • Ubiquitination at Lys 297
  • Modification sites at PhosphoSitePlus

Other Protein References for HPD Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for HPD Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the 4HPPD family.
  • Belongs to the 4HPPD family.
genes like me logo Genes that share domains with HPD: view

No data available for Gene Families for HPD Gene

Function for HPD Gene

Molecular function for HPD Gene

GENATLAS Biochemistry:
4-hydroxyphenylpyruvate dioxygenase,predominantly expressed in liver,catalyzing the second step of tyrosine catabolism
UniProtKB/Swiss-Prot CatalyticActivity:
4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2).
UniProtKB/Swiss-Prot Function:
Key enzyme in the degradation of tyrosine.

Enzyme Numbers (IUBMB) for HPD Gene

Gene Ontology (GO) - Molecular Function for HPD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016701 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen IEA --
genes like me logo Genes that share ontologies with HPD: view
genes like me logo Genes that share phenotypes with HPD: view

Human Phenotype Ontology for HPD Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

No data available for Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for HPD Gene

Localization for HPD Gene

Subcellular locations from

Jensen Localization Image for HPD Gene COMPARTMENTS Subcellular localization image for HPD gene
Compartment Confidence
cytosol 5
extracellular 5
nucleus 4
mitochondrion 2
plasma membrane 1

Gene Ontology (GO) - Cellular Components for HPD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with HPD: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for HPD Gene

Pathways & Interactions for HPD Gene

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

UniProtKB/Swiss-Prot P32754-HPPD_HUMAN

  • Pathway: Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 3/6.

Gene Ontology (GO) - Biological Process for HPD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006572 tyrosine catabolic process ISS --
GO:0009072 aromatic amino acid family metabolic process IEA --
genes like me logo Genes that share ontologies with HPD: view

No data available for SIGNOR curated interactions for HPD Gene

Drugs & Compounds for HPD Gene

(6) Drugs for HPD Gene - From: DrugBank, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nitisinone Approved, Investigational Pharma inhibitor, Target 14
(1-Tert-Butyl-5-Hydroxy-1h-Pyrazol-4-Yl)-(6-Methanesulfonyl-4'-Methoxy-2-Methyl-Biphenyl-3-Yl)-Methanone Experimental Pharma Target 0
Phenylpyruvic acid Experimental Pharma 0

(15) Additional Compounds for HPD Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • Dioxygen
  • Molecular oxygen
  • O2
  • Oxygen
  • Oxygen molecule
4-Hydroxyphenylpyruvic acid
  • (p-hydroxyphenyl)-Pyruvate
  • (p-hydroxyphenyl)-Pyruvic acid
  • (p-Hydroxyphenyl)pyruvate
  • (p-Hydroxyphenyl)pyruvic acid
  • 3-(4-Hydroxyphenyl)-2-oxo-propanoate
carbon dioxide
  • Carbon oxide
  • Carbon-12 dioxide
  • Carbonic acid anhydride
  • Carbonic acid gas
  • Carbonic anhydride
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
Homogentisic acid
  • (2,5-dihydroxyphenyl)-Acetate
  • (2,5-dihydroxyphenyl)-Acetic acid
  • 2,5-Dihydroxy-a-toluate
  • 2,5-Dihydroxy-a-toluic acid
  • 2,5-Dihydroxy-alpha-toluate
genes like me logo Genes that share compounds with HPD: view

Transcripts for HPD Gene

Unigene Clusters for HPD Gene

4-hydroxyphenylpyruvate dioxygenase:
Representative Sequences:

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

No ASD Table

Relevant External Links for HPD Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HPD Gene

mRNA expression in normal human tissues for HPD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Liver (x41.5) and Kidney - Cortex (x8.1).

Protein differential expression in normal tissues from HIPED for HPD Gene

This gene is overexpressed in Liver, secretome (56.8) and Liver (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for HPD Gene

SOURCE GeneReport for Unigene cluster for HPD Gene Hs.2899

genes like me logo Genes that share expression patterns with HPD: view

Protein tissue co-expression partners for HPD Gene

No data available for mRNA Expression by UniProt/SwissProt for HPD Gene

Orthologs for HPD Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HPD Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia HPD 35
  • 90.67 (n)
  • 92.62 (a)
HPD 36
  • 92 (a)
(Canis familiaris)
Mammalia HPD 35
  • 90.25 (n)
  • 92.11 (a)
HPD 36
  • 92 (a)
(Mus musculus)
Mammalia Hpd 35
  • 86.09 (n)
  • 89.82 (a)
Hpd 16
Hpd 36
  • 90 (a)
(Pan troglodytes)
Mammalia HPD 35
  • 99.49 (n)
  • 99.75 (a)
HPD 36
  • 99 (a)
(Rattus norvegicus)
Mammalia Hpd 35
  • 86.34 (n)
  • 89.82 (a)
(Monodelphis domestica)
Mammalia HPD 36
  • 76 (a)
(Ornithorhynchus anatinus)
Mammalia HPD 36
  • 72 (a)
(Gallus gallus)
Aves HPD 35
  • 75.77 (n)
  • 77.58 (a)
HPD 36
  • 76 (a)
(Anolis carolinensis)
Reptilia HPD 36
  • 68 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hpd 35
  • 68.56 (n)
  • 76.03 (a)
Str.8493 35
African clawed frog
(Xenopus laevis)
Amphibia MGC68535 35
(Danio rerio)
Actinopterygii hpdb 35
  • 68.97 (n)
  • 72.05 (a)
zgc56326 35
hpdb 36
  • 70 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8483 35
fruit fly
(Drosophila melanogaster)
Insecta CG11796 37
  • 63 (a)
CG11796 35
  • 65.09 (n)
  • 62.63 (a)
CG11796 36
  • 62 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004802 35
  • 63.52 (n)
  • 66.14 (a)
(Caenorhabditis elegans)
Secernentea C31H2.4 37
  • 41 (a)
T21C12.2 37
  • 61 (a)
hpd-1 35
  • 59.3 (n)
  • 62.11 (a)
hpd-1 36
  • 60 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons PDS1 35
  • 48.82 (n)
  • 39.66 (a)
(Oryza sativa)
Liliopsida Os02g0168100 35
  • 57.12 (n)
  • 49.48 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10805 35
bread mold
(Neurospora crassa)
Ascomycetes NCU01830 35
  • 60.85 (n)
  • 56.95 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 60 (a)
CSA.7220 36
  • 61 (a)
Species with no ortholog for HPD:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • 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)
  • 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)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for HPD Gene

Gene Tree for HPD (if available)
Gene Tree for HPD (if available)

Paralogs for HPD Gene

Paralogs for HPD Gene

genes like me logo Genes that share paralogs with HPD: view

Variants for HPD Gene

Sequence variations from dbSNP and Humsavar for HPD Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
VAR_015444 -
VAR_015445 Tyrosinemia 3 (TYRSN3)
VAR_015446 -
VAR_015447 Tyrosinemia 3 (TYRSN3)
VAR_015448 Tyrosinemia 3 (TYRSN3)

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

Variant ID Type Subtype PubMed ID
nsv899567 CNV Gain 21882294
nsv911 CNV Loss 18451855
nsv899568 CNV Gain 21882294
nsv912 CNV Insertion 18451855
esv2433173 CNV Deletion 19546169
dgv322e199 CNV Deletion 23128226
esv2164211 CNV Deletion 18987734
esv2746496 CNV Deletion 23290073
esv1346224 CNV Deletion 17803354

Variation tolerance for HPD Gene

Residual Variation Intolerance Score: 50.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.39; 63.61% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HPD Gene

Human Gene Mutation Database (HGMD)

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

Disorders for HPD Gene

MalaCards: The human disease database

(19) MalaCards diseases for HPD Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
tyrosinemia, type iii
  • tyrosinemia type iii
  • tyrosinemia, type iii
arthropathy, progressive pseudorheumatoid, of childhood
  • spondyloepiphyseal dysplasia tarda with progressive arthropathy
keratoconus 1
  • ktcn1
corneal dystrophy, posterior polymorphous, 1
  • posterior polymorphous corneal dystrophy
- elite association - COSMIC cancer census association via MalaCards
Search HPD in MalaCards View complete list of genes associated with diseases


  • Hawkinsinuria (HAWK) [MIM:140350]: An inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine. {ECO:0000269 PubMed:11073718}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild mental retardation. {ECO:0000269 PubMed:10942115, ECO:0000269 PubMed:11073718}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for HPD Gene

tyrosinemia,type III

Relevant External Links for HPD

Genetic Association Database (GAD)
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with HPD: view

Publications for HPD Gene

  1. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. (PMID: 11073718) Tomoeda K. … Endo F. (Mol. Genet. Metab. 2000) 3 4 23 67
  2. Alkaptonuric ochronosis with aortic valve and joint replacements and femoral fracture: a case report and literature review. (PMID: 15931360) Fisher A.A. … Davis M.W. (Clin Med Res 2004) 23 25 26
  3. 4-Hydroxyphenylpyruvate dioxygenase as a drug discovery target. (PMID: 14668946) Yang D.Y. (Drug News Perspect. 2003) 23 25 26
  4. Tyrosinemia I, a model for human diseases mediated by 2-oxoacid-utilizing dioxygenases: hepatotoxin suppression by NTBC does not normalize hepatic collagen metabolism. (PMID: 12142814) Hanauske-Abel H.M. … Levy J. (J. Pediatr. Gastroenterol. Nutr. 2002) 23 25 26
  5. Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. (PMID: 18422479) Santra S. … Baumann U. (Expert Opin Pharmacother 2008) 25 26

Products for HPD Gene

Sources for HPD Gene