Homo sapiens complex locus HPD, encoding 4-hydroxyphenylpyruvate dioxygenase.
SUMMARY back to top
RefSeq summary
[HPD] 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].

RefSeq annotates 2 representative transcripts (NM included in AceView variants .a and .b), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 4 spliced variants.

AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is well expressed, 1.3 times the average gene in this release. The sequence of this gene is defined by 160 GenBank accessions from 143 cDNA clones, some from liver (seen 58 times), eye (9), hepatocellular carcinoma, cell line (8), kidney (8), hippocampus (7), large cell carcinoma (7), liver and spleen (7) and 20 other tissues. We annotate structural defects or features in 5 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 18 distinct gt-ag introns. Transcription produces 4 alternatively spliced mRNAs. There are 3 probable alternative promotors, 3 non overlapping alternative last exons and 2 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, overlapping exons with different boundaries, splicing versus retention of one intron. 112 bp of this gene are antisense to spliced gene bluchy, raising the possibility of regulated alternate expression.
Note that mRNA .cAug10 was found in vivo, although it is a predicted target of nonsense mediated mRNA decay (NMD).
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant bAug10).
Function: There are 8 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (OMIM: Hawkinsinuria; Tyrosinemia, type III; Other sources: Tyrosinemias), proposed to participate in pathways (Metabolic pathways, Phenylalanine metabolism, Tyrosine metabolism, Ubiquinone and other terpenoid-quinone biosynthesis) and processes (aromatic amino acid family metabolic process, L-phenylalanine catabolic process, oxidation reduction, tyrosine catabolic process). Proteins are expected to have molecular functions (4-hydroxyphenylpyruvate dioxygenase activity, metal ion binding, oxidoreductase activity) and to localize in various compartments (cytosol, endoplasmic reticulum, endoplasmic reticulum membrane, Golgi apparatus, Golgi membrane).
Protein coding potential: 3 spliced mRNAs putatively encode good proteins, altogether 3 different isoforms (3 complete), some containing Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily domain [Pfam], a vacuolar domain, a coiled coil stretch [Psort2]. The remaining mRNA variant (spliced) appears not to encode a good protein. Finally proteins from this gene may be modulated by acetylation; phosphorylation; ubiquitination, as detailed at PhosphoSite.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 12, links to other databases and other names
Map: This gene HPD maps on chromosome 12, at 12q24-qter according to Entrez Gene. In AceView, it covers 49.09 kb, from 122326516 to 122277427 (NCBI 37, August 2010), on the reverse strand.
Links to: manual annotations from OMIM_140350, OMIM_276710, KEGG_00130, KEGG_00350, KEGG_00360, KEGG_01100, PhosphoSite, the SNP view, gene overviews from Entrez Gene 3242, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: The gene is also known as HPD, PPD, 4HPPD, GLOD3, 4-HPPD or HPPDASE, LOC3242. It has been described as 4-hydroxyphenylpyruvate dioxygenase, glyoxalase domain containing 3, 4-hydroxyphenylpyruvic acid oxidase.
EC number: This gene encodes protein number:
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene Hpd (e=0.0).
The closest C.elegans gene, according to BlastP, is the AceView/WormGene hpd-1 (e= 10-139), which may contain interesting functional annotation.
The closest A.thaliana gene, according to BlastP, is the AceView gene PDS1 (e=3 10-46), which may contain interesting functional annotation
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
aAug10 1551 bp 393 aa 170 bp 199 bp 2kb possibly including promoter 19465 bp 1kb
bAug10 1898 bp 354 aa 632 bp 201 bp 51 bp 2kb including Promoter 49084 bp 1kb
cAug10 581 bp 49 aa 31 bp 400 bp 2kb including Promoter 2257 bp 1kb
dAug10 778 bp 81 aa 279 bp 253 bp 2kb 8583 bp 1kb

Gene neighbors and Navigator on chromosome 12q24-qter back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications        
Annotated mRNA diagrams back to top
Bibliography:               8 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DC

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

If you know more about this gene, or found errors, please share your knowledge. Thank you !