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

    Gene ID: 3242, updated on 27-Nov-2024

    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; HPPD; 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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (121839527..121888611, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (121836201..121884910, complement)
    RS_2024_09 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 transmembrane protein 120B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122216872-122217390 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122217391-122217909 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7182 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7183 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4988 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122227166-122227882 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7184 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7185 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122230665-122231496 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122231502-122232042 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122232583-122233123 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7187 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122235825-122236366 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122236367-122236906 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122236907-122237446 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122237447-122237986 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4992 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4993 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7188 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7189 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7190 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4994 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4995 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4996 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4997 Neighboring gene long intergenic non-protein coding RNA 1089 Neighboring gene ras homolog family member F, filopodia associated Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122248237-122249046 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122249091-122249703 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4999 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122252006-122252512 Neighboring gene SET domain containing 1B, histone lysine methyltransferase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122276754-122277424 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5000 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122278096-122278765 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:122293687-122294886 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 transcript inducer of AURKA lysosomal degradation Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:122326353-122326966 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:122326967-122327580 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:122349577-122349733 Neighboring gene proteasome 26S subunit, non-ATPase 9 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5001 Neighboring gene RNA, U7 small nuclear 170 pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122362388-122363066 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5002 Neighboring gene cilia and flagella associated protein 251 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122396110-122396629 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122396630-122397148 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122409067-122409566 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7192 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7193 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7194 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7195 Neighboring gene Sharpr-MPRA regulatory region 10891 Neighboring gene uncharacterized LOC124903038

    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 different catalytic roles of the metal-binding ligands in human 4-hydroxyphenylpyruvate dioxygenase. Huang CW, et al. Biochem J, 2016 May 1. PMID 26936969
    2. Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III. Item CB, et al. Mol Genet Metab, 2007 Aug. PMID 17560158
    3. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Tomoeda K, et al. Mol Genet Metab, 2000 Nov. PMID 11073718
    4. Human 4-hydroxyphenylpyruvate dioxygenase gene (HPD). Rüetschi U, et al. Genomics, 1997 Sep 15. PMID 9325050
    5. 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. Lin JF, et al. PLoS One, 2013. PMID 23950902, Free PMC Article

    See all (33) 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
    		not available
    Tyrosinemia type III
    MedGen: C0268623 OMIM: 276710 GeneReviews: Not available
    		not available

    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)

    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
    		  
    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
    		  
    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
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in endoplasmic reticulum membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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
    p-hydroxyphenylpyruvate dioxygenase
    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
      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/Swiss-Prot
      A0A0B4J1R4, A8K461, B3KQ63, P32754, Q13234
      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_2024_08

    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
    P32754.3 GenPept UniProtKB/Swiss-Prot:P32754

    Gene LinkOut

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

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