HPDL

4-hydroxyphenylpyruvate dioxygenase like, the group of Glyoxalase domain containing family

Basic information

Region (hg38): 1:45326895-45328710

Previous symbols: [ "GLOXD1" ]

Links

ENSG00000186603 ∙ NCBI:84842 ∙ OMIM:618994 ∙ HGNC:28242 ∙ Uniprot:Q96IR7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities; Spastic paraplegia 83, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	32707086; 33188300; 33970200

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPDL gene.

• Inborn_genetic_diseases (50 variants)
• Neurodevelopmental_disorder_with_progressive_spasticity_and_brain_white_matter_abnormalities (32 variants)
• Spastic_paraplegia (28 variants)
• not_provided (27 variants)
• Spastic_paraplegia_83,_autosomal_recessive (6 variants)
• HPDL-related_disorder (2 variants)
• Spastic_ataxia (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPDL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032756.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense	6	20	51	7		84
nonsense	2	4				6
start loss		1				1
frameshift	8	11	1			20
splice donor/acceptor (+/-2bp)						0
Total	16	36	52	9	2

Highest pathogenic variant AF is 0.000051561

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPDL	protein_coding	protein_coding	ENST00000334815	1	1803

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000226	0.511	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.933	197	237	0.830	0.0000150	2311
Missense in Polyphen		63	80.043	0.78708		910
Synonymous	1.21	100	117	0.858	0.00000831	861
Loss of Function	0.592	8	10.0	0.798	6.56e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have dioxygenase activity. {ECO:0000305}.

Recessive Scores

• pRec: 0.157

Intolerance Scores

• loftool: 0.623
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.35

Haploinsufficiency Scores

• pHI: 0.0598
• hipred: N
• hipred_score: 0.272
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.313

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hpdl

Gene ontology

• Biological process: aromatic amino acid family metabolic process;oxidation-reduction process
• Molecular function: 4-hydroxyphenylpyruvate dioxygenase activity;metal ion binding