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  3. HPDL
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Early onset or syndromic epilepsy

Gene: HPDL

Green List (high evidence)
HPDL (4-hydroxyphenylpyruvate dioxygenase like)
EnsemblGeneIds (GRCh38): ENSG00000186603
EnsemblGeneIds (GRCh37): ENSG00000186603
HPDL is in 10 panels

3 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated followingNHS Genomic Medicine Serviceapproval.
Created: 11 Mar 2022, 3:31 p.m. | Last Modified: 11 Mar 2022, 3:31 p.m.
Panel Version: 2.498
Created: 11 Mar 2022, 3:31 p.m.
Last Modified: 11 Mar 2022, 3:31 p.m.
Panel version: 2.498

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: New gene added by Evan Reid (University of Cambridge). There is enough evidence for this gene to be rated Green at the next major review.
Created: 9 Feb 2021, 3:30 p.m. | Last Modified: 9 Feb 2021, 3:30 p.m.
Panel Version: 2.290
Associated with relevant phenotype in OMIM and has a 'probable' disease confidence for 'HPDL Neurodegenerative Disease' in Gene2Phenotype.

At least 34 cases from 21 unrelated families with a paediatric-onset spastic movement disorder and biallelic variants in this gene (PMIDs: 32707086 and 33188300). There is broad clinical variability ranging from severe, neonatal-onset neurodevelopmental delay with neuroimaging findings resembling mitochondrial encephalopathy to milder manifestation of adolescent-onset, isolated HSP. Epilepsy were observed in 20/34 cases - phenotypes were not defined in PMID:32707086 but subjects from PMID:33188300 developed seizures within the first year of life that were typically myoclonic, focal, or tonic and occurred daily to weekly.

Supportive functional studies were reported, including localization of HPDL protein to the mitochondria and muscle fibre abnormalities and a KO mouse model displaying features of seizures, early lethality, smaller brain sizes, and cellular apoptosis.
Created: 9 Feb 2021, 3:29 p.m. | Last Modified: 9 Feb 2021, 3:29 p.m.
Panel Version: 2.289

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613

Publications

Created: 9 Feb 2021, 3:29 p.m.
Last Modified: 9 Feb 2021, 3:29 p.m.
Panel version: 2.289

Evan Reid (University of Cambridge)

Green List (high evidence)

Newly identified gene that can give a phenotype ranging from infantile epileptic encephalopathy to juvenile onset progressive spastic paraplegia.
Sources: Literature
Created: 4 Feb 2021, 3:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability

Publications

Created: 4 Feb 2021, 3:13 p.m.

Panel version: 2.288

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026
  • Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
Clinvar variants
Variants in HPDL
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

20 Mar 2026, Gel status: 3

Removed Tag

Ida Ertmanska (Genomics England Curator)

Tag gene-checked was removed from gene: HPDL.

7 May 2022, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag gene-checked tag was added to gene: HPDL.

11 Mar 2022, Gel status: 3

Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_rating was removed from gene: HPDL.

11 Mar 2022, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to HPDL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

9 Feb 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: HPDL were changed from spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613

9 Feb 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: HPDL were set to PMID: 32707086; 33188300

9 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: hpdl has been classified as Amber List (Moderate Evidence).

9 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: HPDL.

4 Feb 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Evan Reid (University of Cambridge)

gene: HPDL was added gene: HPDL was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HPDL were set to PMID: 32707086; 33188300 Phenotypes for gene: HPDL were set to spastic paraplegia; spastic tetraplegia; microcephaly; brain atrophy; epilepsy; severe intellectual; motor disability Penetrance for gene: HPDL were set to Complete Review for gene: HPDL was set to GREEN