HPDL: 4-Hydroxyphenylpyruvate Dioxygenase-Like Gene
A gene encoding a putative dioxygenase involved in aromatic amino acid metabolism and linked to neurodevelopmental disorders.
Gene Information Card
| Symbol | HPDL |
|---|---|
| Full Name | 4-Hydroxyphenylpyruvate Dioxygenase-Like |
| Gene Type | Protein-coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 84842 ncbi.nlm.nih.gov/gene/84842 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q96IR7 |
| OMIM ID | 618994 |
| HGNC ID | 28203 |
| Aliases | HPDL1, MGC13170 |
Description
HPDL (4-Hydroxyphenylpyruvate Dioxygenase-Like) encodes a protein that shares sequence similarity with 4-hydroxyphenylpyruvate dioxygenase (HPD), an enzyme involved in tyrosine catabolism. The HPDL protein is predicted to function as a dioxygenase, though its exact biochemical substrate remains under investigation. Biallelic loss-of-function mutations in HPDL cause an autosomal recessive neurodevelopmental disorder characterized by progressive spasticity, developmental delay, and white matter abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) | Biallelic loss-of-function mutations in HPDL lead to deficiency of the HPDL protein, impairing mitochondrial function and causing neurodegeneration. | OMIM #618994; ClinVar; PMID: 31730859 |
| Spastic paraplegia, intellectual disability, and seizures | HPDL variants disrupt normal neuronal development and myelination, resulting in motor and cognitive deficits. | ClinVar; PMID: 31730859 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 3.2 nTPM | Low |
| Liver | 1.8 nTPM | Low |
| Kidney | 1.5 nTPM | Low |
| Heart | 1.2 nTPM | Low |
| Testis | 0.9 nTPM | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 2.5 nTPM | Neuronal model |
| HEK293 (embryonic kidney) | 1.0 nTPM | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.8 nTPM | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense (start loss) | Rare | Loss of protein translation; associated with NEDSWMA |
| c.152C>T (p.Pro51Leu) | Missense | Rare | Impaired protein stability; pathogenic in ClinVar |
| c.403C>T (p.Arg135*) | Nonsense | Rare | Premature stop; loss-of-function; reported in affected individuals |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, start loss) cause HPDL deficiency, leading to neurodevelopmental disorder.
Gain of Function (GOF)
No evidence of gain-of-function mutations in HPDL.
Dominant Negative (DN)
No evidence of dominant-negative effects; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • catalytic activity (GO:0003824) | • oxidoreductase activity, acting on single donors with incorporation of molecular oxygen (GO:0016702) |
| • mitochondrion (GO:0005739) | • tyrosine catabolic process (GO:0006572) |
Pathways
• Tyrosine metabolism (KEGG: hsa00350)
• Phenylalanine and tyrosine biosynthesis (Reactome: R-HSA-8978868)
Protein Summary
The HPDL protein (UniProt Q96IR7) is a 393-amino acid putative dioxygenase localized to mitochondria. It contains a conserved 2-oxoglutarate-dependent dioxygenase domain. Although its precise enzymatic function is not fully defined, it is thought to participate in aromatic amino acid metabolism. Loss of HPDL leads to mitochondrial dysfunction and oxidative stress, particularly affecting the central nervous system.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HPDL Knockout HEK293 Cell Line | EDJ-KQ1214 | Human | 84842 | 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 |
| HPDL Knockout HCT 116 Cell Line | EDJ-KQ74595 | Human | 84842 | Details Get a Quote |
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