HPD Gene (4-Hydroxyphenylpyruvate Dioxygenase)
Genetic, structural, and clinical insights into HPD-related disorders
Gene Information Card
| Symbol | HPD |
|---|---|
| Full Name | 4-hydroxyphenylpyruvate dioxygenase |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 3242 ncbi.nlm.nih.gov/gene/3242 |
| Ensembl ID | ENSG00000110514 |
| UniProt ID | P32754 |
| OMIM ID | 609695 |
| HGNC ID | 5164 |
| Aliases | 4HPPD, HPPD, PPD |
Description
The HPD gene encodes 4-hydroxyphenylpyruvate dioxygenase, a key enzyme in tyrosine catabolism. It catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate, a step required for the breakdown of tyrosine. Mutations in HPD lead to metabolic disorders such as tyrosinemia type III and hawkinsinuria. The enzyme is also a target for herbicides and certain therapeutic agents.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tyrosinemia type III | Loss-of-function mutations in HPD cause deficiency of 4-hydroxyphenylpyruvate dioxygenase, leading to accumulation of tyrosine and 4-hydroxyphenylpyruvate. | OMIM 276710; ClinVar |
| Hawkinsinuria | Specific mutations (e.g., p.Ala33Thr) result in an abnormal intermediate (hawkinsin) due to altered enzyme activity, causing metabolic acidosis and growth retardation. | OMIM 140350; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~ 100) | High |
| Kidney | Moderate (nTPM ~ 20) | Moderate |
| Small intestine | Low (nTPM ~ 5) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | High | Hepatocellular carcinoma cell line |
| HEK293 (embryonic kidney) | Moderate | Commonly used for expression studies |
| A549 (lung) | Low | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.97A>G (p.Thr33Ala) | Missense | Rare | Associated with hawkinsinuria; alters enzyme activity |
| c.1156C>T (p.Arg386Trp) | Missense | Rare | Reported in tyrosinemia type III; reduces enzyme function |
| c.782delA (p.Asn261Thrfs*24) | Frameshift | Rare | Loss-of-function; causes tyrosinemia type III |
Mutation functional classification
Loss of Function (LOF)
Most HPD mutations causing tyrosinemia type III are loss-of-function, leading to reduced or absent enzyme activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HPD.
Dominant Negative (DN)
Hawkinsinuria mutations may exert a dominant-negative effect by producing an abnormal enzyme that interferes with normal function, though the exact mechanism is still under study.
View complete mutation data：
Gene Ontology (GO)
| • 4-hydroxyphenylpyruvate dioxygenase activity | • iron ion binding |
| • catalytic activity | • oxidation-reduction process |
| • tyrosine catabolic process |
Pathways
• Tyrosine metabolism
• Phenylalanine and tyrosine catabolism
Protein Summary
The HPD protein is a homodimeric enzyme that requires ferrous iron as a cofactor. It catalyzes the oxidative decarboxylation of 4-hydroxyphenylpyruvate to homogentisate, a key step in tyrosine degradation. The enzyme is primarily expressed in the liver and kidney. Structural studies reveal a conserved active site that is targeted by herbicides like mesotrione. Defects in HPD lead to metabolic disorders, and the protein is also a potential therapeutic target for type II tyrosinemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HPDL Knockout HEK293 Cell Line | EDJ-KQ1214 | Human | 84842 | Details Get a Quote |
| HPD Knockout HEK293 Cell Line | EDJ-KQ4931 | Human | 3242 | Details Get a Quote |
| HPDL Knockout A-549 Cell Line | EDJ-KQ21834 | Human | 84842 | Details Get a Quote |
| HPDL Knockout HeLa Cell Line | EDJ-KQ21836 | Human | 84842 | Details Get a Quote |
| HPD Knockout A-549 Cell Line | EDJ-KQ26559 | Human | 3242 | Details Get a Quote |
| HPD Knockout HeLa Cell Line | EDJ-KQ27771 | Human | 3242 | Details Get a Quote |
| HPD Knockout HCT 116 Cell Line | EDJ-KQ70513 | Human | 3242 | Details Get a Quote |
| HPDL Knockout HCT 116 Cell Line | EDJ-KQ74595 | Human | 84842 | Details Get a Quote |
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