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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 1.13.11.27 4 56
  • 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 Phenylalanine metabolism and Viral mRNA Translation. Gene Ontology (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.

Additional gene information for HPD Gene

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

Genomics for HPD Gene

GeneHancer (GH) Regulatory Elements for HPD Gene

Promoters and enhancers for HPD 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
GH12I121887 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 550.8 -0.5 -480 2.3 CLOCK MLX FEZF1 DMAP1 YY1 ZNF213 E2F8 ZNF143 SP3 MEF2D PSMD9 ENSG00000256950 HPD RSRC2 ZCCHC8 KNTC1 ENSG00000272849 LINC01089 SETD1B SPPL3
GH12I121858 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 582.4 +29.0 28996 2.4 PKNOX1 FOXA2 ARID4B DMAP1 ZNF48 ETS1 YY1 ATF7 FOS RXRA HPD LOC105370035 SETD1B LINC01089 PSMD9 ENSG00000256950 WDR66 TMEM120B ENSG00000278084
GH12I121783 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 15.6 +92.6 92619 24.5 CLOCK MLX FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 ENSG00000272849 SETD1B RHOF ZCCHC8 RSRC2 PSMD9 ANAPC5 KNTC1 LINC01089 HPD
GH12I121708 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE 11.3 +175.2 175163 9.8 PKNOX1 FOXA2 ARNT ARID4B SIN3A FEZF1 DMAP1 YY1 POLR2B ZNF143 TMEM120B KDM2B LOC101928346 HPD PSMD9 ENSG00000256950 MORN3 HNF1A-AS1 ENSG00000272849
GH12I122265 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 10 -377.8 -377752 2.6 CLOCK MLX ZFP64 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ENSG00000256861 VPS33A RSRC2 C12orf65 ZCCHC8 ENSG00000235423 ANAPC5 ENSG00000272849 SETD1B LINC01089
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around HPD on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HPD gene promoter:

Genomic Locations for HPD Gene

Genomic Locations for HPD Gene
chr12:121,839,527-121,888,611
(GRCh38/hg38)
Size:
49,085 bases
Orientation:
Minus strand
chr12:122,277,433-122,326,517
(GRCh37/hg19)

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:
    P32754-HPPD_HUMAN
    Recommended name:
    4-hydroxyphenylpyruvate dioxygenase
    Protein Accession:
    P32754
    Secondary Accessions:
    • A8K461
    • B3KQ63
    • Q13234

    Protein attributes for HPD Gene

    Size:
    393 amino acids
    Molecular mass:
    44934 Da
    Cofactor:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for HPD Gene

Selected DME Specific Peptides for HPD Gene

P32754:
  • GLETGSR
  • FHRFWSVDD
  • TYGDTTHT
  • VGNAKQAA
  • DHIVGNQPD
  • GKKKSQI
  • HGDGVKD
  • KMPINEPA
  • GFGAGNF
  • VTFWVGNA
  • AYRGLETG
  • GAGVQHIAL
  • LLQIFTKP

Post-translational modifications for HPD Gene

Other Protein References for HPD Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for HPD Gene

Gene Families for HPD Gene

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

Graphical View of Domain Structure for InterPro Entry

P32754

UniProtKB/Swiss-Prot:

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

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

Phenotypes From GWAS Catalog for HPD Gene

Gene Ontology (GO) - Molecular Function for HPD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003868 4-hydroxyphenylpyruvate dioxygenase activity EXP,ISS --
GO:0016491 oxidoreductase activity IEA --
GO:0016701 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen IEA --
GO:0046872 metal ion binding IEA --
GO:0051213 dioxygenase activity 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

Clone Products

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

Localization for HPD Gene

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 HPD gene
Compartment Confidence
extracellular 5
cytosol 5
nucleus 4
endoplasmic reticulum 3
golgi apparatus 3
mitochondrion 2
plasma membrane 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear speckles (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HPD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IBA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IBA --
GO:0005794 Golgi apparatus IEA --
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:0006559 L-phenylalanine catabolic process TAS --
GO:0006572 tyrosine catabolic process IBA,ISS --
GO:0009072 aromatic amino acid family metabolic process IEA --
GO:0055114 oxidation-reduction 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

(8) 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 Target, inhibitor 15
Oxygen Approved, Vet_approved Pharma 0
Carbon dioxide Approved, Investigational, Vet_approved Pharma 0
(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

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
4-Hydroxyphenylpyruvic acid
  • (p-hydroxyphenyl)-Pyruvate
  • (p-hydroxyphenyl)-Pyruvic acid
  • (p-Hydroxyphenyl)pyruvate
  • (p-Hydroxyphenyl)pyruvic acid
  • 3-(4-Hydroxyphenyl)-2-oxo-propanoate
156-39-8
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
15438-31-0
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
451-13-8
Ortho-Hydroxyphenylacetic acid
  • (2-Hydroxyphenyl)acetate
  • (2-Hydroxyphenyl)acetic acid
  • (O-hydroxyphenyl)-Acetate
  • (O-hydroxyphenyl)-Acetic acid
  • (O-Hydroxyphenyl)acetate
614-75-5
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:

Clone Products

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

No ASD Table

Relevant External Links for HPD Gene

GeneLoc Exon Structure for
HPD
ECgene alternative splicing isoforms for
HPD

Expression for HPD Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for HPD Gene



Protein tissue co-expression partners for HPD Gene

NURSA nuclear receptor signaling pathways regulating expression of HPD Gene:

HPD

SOURCE GeneReport for Unigene cluster for HPD Gene:

Hs.2899

Evidence on tissue expression from TISSUES for HPD Gene

  • Liver(4.8)
  • Kidney(2.8)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HPD Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cerebellum
  • eye
  • head
Abdomen:
  • liver
Limb:
  • ankle
  • digit
  • foot
  • hand
  • knee
  • lower limb
  • upper limb
General:
  • hair
  • skin
genes like me logo Genes that share expression patterns with HPD: view

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
chimpanzee
(Pan troglodytes)
Mammalia HPD 33 34
  • 99.49 (n)
cow
(Bos Taurus)
Mammalia HPD 33 34
  • 90.67 (n)
dog
(Canis familiaris)
Mammalia HPD 33 34
  • 90.25 (n)
rat
(Rattus norvegicus)
Mammalia Hpd 33
  • 86.34 (n)
mouse
(Mus musculus)
Mammalia Hpd 33 16 34
  • 86.09 (n)
oppossum
(Monodelphis domestica)
Mammalia HPD 34
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HPD 34
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves HPD 33 34
  • 75.77 (n)
lizard
(Anolis carolinensis)
Reptilia HPD 34
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hpd 33
  • 68.56 (n)
Str.8493 33
African clawed frog
(Xenopus laevis)
Amphibia MGC68535 33
zebrafish
(Danio rerio)
Actinopterygii hpdb 33 34
  • 68.97 (n)
zgc56326 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8483 33
fruit fly
(Drosophila melanogaster)
Insecta CG11796 35 33 34
  • 65.09 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004802 33
  • 63.52 (n)
worm
(Caenorhabditis elegans)
Secernentea T21C12.2 35
  • 61 (a)
hpd-1 33 34
  • 59.3 (n)
C31H2.4 35
  • 41 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons PDS1 33
  • 48.82 (n)
rice
(Oryza sativa)
Liliopsida Os02g0168100 33
  • 57.12 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7220 34
  • 61 (a)
OneToMany
-- 34
  • 60 (a)
OneToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU01830 33
  • 60.85 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10805 33
Species where no ortholog for HPD was found in the sources mined by GeneCards:
  • 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

ENSEMBL:
Gene Tree for HPD (if available)
TreeFam:
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 Variation AA Info Type
rs1154510 pathogenic, benign, 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency, 4-Hydroxyphenylpyruvate dioxygenase deficiency 121,857,429(-) T/C 5_prime_UTR_variant, coding_sequence_variant, missense_variant
rs117079110 likely-benign, Hypertyrosinemia, 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency 121,856,354(-) G/A coding_sequence_variant, synonymous_variant
rs11833399 benign, Hypertyrosinemia, 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency 121,854,779(-) C/T coding_sequence_variant, missense_variant
rs137852865 pathogenic, 4-Hydroxyphenylpyruvate dioxygenase deficiency, Tyrosinemia 3 (TYRSN3) [MIM:276710] 121,849,726(-) T/C coding_sequence_variant, missense_variant
rs137852866 pathogenic, 4-Hydroxyphenylpyruvate dioxygenase deficiency 121,846,919(-) A/C coding_sequence_variant, stop_gained

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

Variant ID Type Subtype PubMed ID
dgv322e199 CNV deletion 23128226
dgv883n106 CNV deletion 24896259
esv1346224 CNV deletion 17803354
esv2164211 CNV deletion 18987734
esv2433173 CNV deletion 19546169
esv2746496 CNV deletion 23290073
esv3549898 CNV deletion 23714750
esv3549901 CNV deletion 23714750
nsv957277 CNV deletion 24416366
nsv912 CNV insertion 18451855
nsv911 CNV deletion 18451855
nsv472039 CNV novel sequence insertion 20440878
nsv1160065 CNV deletion 26073780
nsv1145887 CNV deletion 26484159
nsv1127299 CNV deletion 24896259
nsv1070135 CNV deletion 25765185
esv3892268 CNV loss 25118596
esv3630960 CNV loss 21293372

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)

Additional Variant Information for HPD Gene

Human Gene Mutation Database (HGMD)
HPD
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HPD

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

Disorders for HPD Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
tyrosinemia, type iii
  • tyrsn3
hawkinsinuria
  • 4-alpha-hydroxyphenylpyruvate hydroxylase deficiency
tyrosinemia
  • hereditary tyrosinemia
tyrosinemia, type i
  • tyrsn1
prostate calculus
  • calculus of prostate
- elite association - COSMIC cancer census association via MalaCards
Search HPD in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HPPD_HUMAN
  • 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

Additional Disease Information for HPD

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 (Molecular genetics and metabolism 2000) 3 4 22 58
  2. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. (PMID: 10942115) Rüetschi U … Holme E (Human genetics 2000) 3 4 22 58
  3. Human 4-hydroxyphenylpyruvate dioxygenase gene (HPD). (PMID: 9325050) Rüetschi U … Lindstedt S (Genomics 1997) 3 4 22 58
  4. Regional assignment of the human 4-hydroxyphenylpyruvate dioxygenase gene (HPD) to 12q24-->qter by fluorescence in situ hybridization. (PMID: 8521727) Stenman G … Lindstedt S (Cytogenetics and cell genetics 1995) 3 4 22 58
  5. Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD). (PMID: 7851880) Awata H … Matsuda I (Genomics 1994) 3 4 22 58

Products for HPD Gene

Sources for HPD Gene