HPDL
Chr 1AR4-hydroxyphenylpyruvate dioxygenase like
Also known as: 4-HPPD-L, GLOXD1, NEDSWMA, SPG83
The protein is an iron-dependent mitochondrial dioxygenase that catalyzes the conversion of 4-hydroxyphenylpyruvate to 4-hydroxymandelate in coenzyme Q10 biosynthesis from tyrosine. Biallelic mutations cause autosomal recessive pediatric-onset spastic movement disorder with neurodevelopmental features and brain white matter abnormalities, also known as spastic paraplegia 83. The gene shows low constraint against loss-of-function variants (pLI near 0), consistent with its recessive inheritance pattern.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
144 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 8 | 6 | 7 | 0 | 21 |
Likely Pathogenic | 17 | 18 | 2 | 0 | 37 |
VUS | 1 | 58 | 10 | 0 | 69 |
Likely Benign | 0 | 7 | 0 | 3 | 10 |
Benign | 0 | 0 | 1 | 2 | 3 |
Conflicting | — | 4 | |||
| Total | 26 | 89 | 20 | 5 | 144 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HPDL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools