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

Summary

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

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway.
Title: The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway.
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.
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).
Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity.
Title: Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity.
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.
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.
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.
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.
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.
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.

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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 EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:455126 (e-PCR)
- UniSTS:157451

GDB:455130 (e-PCR)
- UniSTS:157452

STS-U29895 (e-PCR)
- UniSTS:46927

RK1290_1291 (e-PCR)
- UniSTS:22890

G60359 (e-PCR)
- UniSTS:137615

D12S1349 (e-PCR)
- UniSTS:31135

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	IEA Inferred from Electronic Annotation more info
enables 4-hydroxyphenylpyruvate dioxygenase activity	ISS Inferred from Sequence or Structural Similarity more info
enables dioxygenase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	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 aromatic amino acid metabolic 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	IEA Inferred from Electronic Annotation more info
involved_in tyrosine catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in tyrosine catabolic process	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
is_active_in Golgi membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info

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

EC 1.13.11.27

NP_002141.2

EC 1.13.11.27

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

NG_016461.2 RefSeqGene

Range

34752..54084

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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