HPDL

Protein identityUniProt · HPA

UniProt accession

Q96IR7

Gene

HPDL

Ensembl

ENSG00000186603

Chromosome

1

Canonical length

371 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Mitochondria

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

371 residues, UniProt reviewed canonical sequence.

>Q96IR7|HPDL
     1  MAAPALRLCH IAFHVPAGQP LARNLQRLFG FQPLASREVD GWRQLALRSG DAVFLVNEGA
    61  GSGEPLYGLD PRHAVPSATN LCFDVADAGA ATRELAALGC SVPVPPVRVR DAQGAATYAV
   121  VSSPAGILSL TLLERAGYRG PFLPGFRPVS SAPGPGWVSR VDHLTLACTP GSSPTLLRWF
   181  HDCLGFCHLP LSPGEDPELG LEMTAGFGLG GLRLTALQAQ PGSIVPTLVL AESLPGATTR
   241  QDQVEQFLAR HKGPGLQHVG LYTPNIVEAT EGVATAGGQF LAPPGAYYQQ PGKERQIRAA
   301  GHEPHLLARQ GILLDGDKGK FLLQVFTKSL FTEDTFFLEL IQRQGATGFG QGNIRALWQS
   361  VQEQSARSQE A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HPDL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HPDL.

Disease | AllUniProt

Conditions HPDL is implicated in, by any mechanism.

• Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) MIM:619026
• Spastic paraplegia 83, autosomal recessive (SPG83) MIM:619027

Disease | GeneticClinVar

48 pathogenic / likely-pathogenic of 125 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spastic paraplegia
• Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
• Inborn genetic diseases
• Spastic paraplegia 83, autosomal recessive
• Spastic ataxia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.43

gnomAD pLI

0

gnomAD missense Z

0.93

DepMap mean gene effect

-0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aromatic amino acid metabolic process

Molecular functions

• 4-hydroxyphenylpyruvate dioxygenase activity
• metal ion binding
• 4-hydroxymandelate synthase activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• 4-hydroxyphenylpyruvate dioxygenase
• Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase
• Vicinal oxygen chelate (VOC), core domain
• 4-hydroxyphenylpyruvate dioxygenase, C-terminal
• 4-hydroxyphenylpyruvate dioxygenase, N-terminal

KeywordsUniProt

• Dioxygenase
• Hereditary spastic paraplegia
• Intellectual disability
• Iron
• Metal-binding
• Mitochondrion
• Neurodegeneration
• Oxidoreductase
• Repeat