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HPD 4-hydroxyphenylpyruvate dioxygenase [ Homo sapiens (human) ]

Gene ID: 3242, updated on 29-Mar-2023

Summary

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Official Symbol
HPDprovided by HGNC
Official Full Name
4-hydroxyphenylpyruvate dioxygenaseprovided by HGNC
Primary source
HGNC:HGNC:5147
See related
Ensembl:ENSG00000158104 MIM:609695; AllianceGenome:HGNC:5147
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
PPD; 4HPPD; GLOD3; 4-HPPD; HPPDASE
Summary
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]
Expression
Biased expression in liver (RPKM 441.7) and kidney (RPKM 174.9) See more
Orthologs
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Genomic context

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See HPD in Genome Data Viewer
Location:
12q24.31
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (121839527..121888611, complement)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (121836201..121884910, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (122277433..122326517, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene SET domain containing 1B, histone lysine methyltransferase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122252006-122252512 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122276754-122277424 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122278096-122278765 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:122293687-122294886 Neighboring gene uncharacterized LOC105370035 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122297907-122298424 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122298425-122298941 Neighboring gene Sharpr-MPRA regulatory region 2080 Neighboring gene Sharpr-MPRA regulatory region 2229 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:122326353-122326966 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:122326967-122327580 Neighboring gene proteasome 26S subunit, non-ATPase 9 Neighboring gene RNA, U7 small nuclear 170 pseudogene

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
  • 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. The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. Banh RS, et al. Nature, 2021 Sep. PMID 34471290, Free PMC Article
  2. Tyrosine metabolic enzyme HPD is decreased and predicts unfavorable outcomes in hepatocellular carcinoma. Yang X, et al. Pathol Res Pract, 2020 Nov. PMID 32891822
  3. Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS). Zhao D, et al. J Pediatr Endocrinol Metab, 2020 Apr 28. PMID 32109208
  4. Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity. Feng AN, et al. J Biochem, 2020 Mar 1. PMID 31722428
  5. 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis. Shan C, et al. Cell Death Dis, 2019 Jul 8. PMID 31285420, Free PMC Article

See all (32) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway.
    Title: The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway.
  2. Tyrosine metabolic enzyme HPD is decreased and predicts unfavorable outcomes in hepatocellular carcinoma.
    Title: Tyrosine metabolic enzyme HPD is decreased and predicts unfavorable outcomes in hepatocellular carcinoma.
  3. Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS).
    Title: Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS).
  4. Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity.
    Title: Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity.
  5. this study reveals HPD as a novel regulator of LKB1-AMPK signaling-mediated HDAC10 nuclear location.
    Title: 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.
  6. Our findings indicate that HPD may be a useful prognostic predictor, and a potential therapeutic target for patients with breast cancer
    Title: HPD overexpression predicts poor prognosis in breast cancer.
  7. The mutagenesis and structural simulation studies demonstrate the critical and unique role of each ligand in the function of HPPD, and which correlates with their respective co-ordination position.
    Title: The different catalytic roles of the metal-binding ligands in human 4-hydroxyphenylpyruvate dioxygenase.
  8. 4-hydroxyphenylpyruvate dioxygenase gene mutation is associated with Hawkinsinuria.
    Title: Hawkinsinuria in two unrelated Greek newborns: identification of a novel variant, biochemical findings and treatment.
  9. Glutamine375 has a critical role for 4-HPPD in orientating the tail and ensuring the conformation of the terminal alpha-helix of the enzyme to maintain the integrity of the active site for biocatalysis.
    Title: The interactions in the carboxyl terminus of human 4-hydroxyphenylpyruvate dioxygenase are critical to mediate the conformation of the final helix and the tail to shield the active site for catalysis.
  10. The IIe335Met allele is equivalent to a null mutation while the Asn241Ser allele results in a partially active enzyme with an uncoupled turnover causing elevated haykinin in urine.
    Title: Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III.
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
Hawkinsinuria
MedGen: C2931042 OMIM: 140350 GeneReviews: Not available
Compare labs
Tyrosinemia type III
MedGen: C0268623 OMIM: 276710 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of metabolic traits in human urine.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
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

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 4-hydroxyphenylpyruvate dioxygenase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables 4-hydroxyphenylpyruvate dioxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 4-hydroxyphenylpyruvate dioxygenase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in L-phenylalanine catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in tyrosine catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
acts_upstream_of_or_within tyrosine catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in tyrosine catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
is_active_in Golgi membrane IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in extracellular exosome HDA PubMed 

General protein information

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Preferred Names
4-hydroxyphenylpyruvate dioxygenase
Names
4-hydroxyphenylpyruvic acid oxidase
glyoxalase domain containing 3
NP_001165464.1
NP_002141.2

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.

Genomic

  1. NG_016461.2 RefSeqGene

    Range
    34752..54084
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001171993.2 → NP_001165464.1  4-hydroxyphenylpyruvate dioxygenase isoform 2

    See identical proteins and their annotated locations for NP_001165464.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC069503, AC079360
    Consensus CDS
    CCDS53839.1
    UniProtKB/Swiss-Prot
    P32754
    Related
    ENSP00000441677.1, ENST00000543163.5
    Conserved Domains (3) summary
    cd07250
    Location:139 → 334
    HPPD_C_like; C-terminal domain of 4-hydroxyphenylpyruvate dioxygenase (HppD) and hydroxymandelate Synthase (HmaS)
    cd08342
    Location:1 → 123
    HPPD_N_like; N-terminal domain of 4-hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate Synthase (HmaS)
    TIGR01263
    Location:1 → 342
    4HPPD; 4-hydroxyphenylpyruvate dioxygenase

  2. NM_002150.3 → NP_002141.2  4-hydroxyphenylpyruvate dioxygenase isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AC079360
    Consensus CDS
    CCDS9224.1
    UniProtKB/TrEMBL
    A0A0B4J1R4
    Related
    ENSP00000289004.4, ENST00000289004.8
    Conserved Domains (1) summary
    TIGR01263
    Location:19 → 381
    4HPPD; 4-hydroxyphenylpyruvate dioxygenase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    121839527..121888611 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    121836201..121884910 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P32754.2 GenPept UniProtKB/Swiss-Prot:P32754

Gene LinkOut

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