HPD

Chr 12ADAR

4-hydroxyphenylpyruvate dioxygenase

Also known as: 4-HPPD, 4HPPD, GLOD3, HPPD, HPPDASE, PPD

NCBI Gene: 3242 ENSG00000158104 UniProt: P32754 OMIM: 609695

The protein encoded by HPD is 4-hydroxyphenylpyruvate dioxygenase, which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate in the tyrosine catabolic pathway. Mutations cause tyrosinemia type 3 and hawkinsinuria, both autosomal recessive disorders affecting amino acid metabolism. The gene shows low constraint to loss-of-function variation (pLI 0.0005), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

HawkinsinuriaMIM #140350

Tyrosinemia, type IIIMIM #276710

UniProtTyrosinemia 3

Clinical highlights

Gene-disease validity (ClinGen)

tyrosinemia type III · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

354

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

Multiple*

Mechanism· G2P

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