HPDL

Chr 1AR

4-hydroxyphenylpyruvate dioxygenase like

Also known as: 4-HPPD-L, GLOXD1, NEDSWMA, SPG83

NCBI Gene: 84842 ENSG00000186603 UniProt: Q96IR7 OMIM: 618994

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this intronless gene localizes to mitochondria, where it may function as 4-hydroxyphenylpyruvate dioxygenase. Clinical studies have identified several bi-allelic variants in this gene that lower the level of the encoded protein and lead to a clinically variable form of pediatric-onset spastic movement disorder. [provided by RefSeq, Aug 2020]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalitiesMIM #619026

Spastic paraplegia 83, autosomal recessiveMIM #619027

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARModerateconsider for supplementary testing

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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.43

LOEUF

LOF

Mechanism· G2P

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GeneReview available — HPDL