QDPR

quinoid dihydropteridine reductase, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 4:17460261-17512206

Links

ENSG00000151552 ∙ NCBI:5860 ∙ OMIM:612676 ∙ HGNC:9752 ∙ Uniprot:P09417 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dihydropteridine reductase deficiency (Definitive), mode of inheritance: AR
• dihydropteridine reductase deficiency (Strong), mode of inheritance: AR
• dihydropteridine reductase deficiency (Supportive), mode of inheritance: AR
• dihydropteridine reductase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphenylalaninemia, BH4-deficient, C	AR	Biochemical	Dietary measures and/or medical treatment (eg, L-dopa, tetrahydrobiopterin) can be beneficial	Biochemical; Neurologic	53532; 49470; 317358; 2785251; 2116088; 7627180; 10029353; 11153907; 11746132; 16917893

ClinVar

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

• Dihydropteridine_reductase_deficiency (315 variants)
• Inborn_genetic_diseases (26 variants)
• not_provided (24 variants)
• not_specified (8 variants)
• QDPR-related_disorder (4 variants)
• BH4-Deficient_Hyperphenylalaninemia (1 variants)
• Hyperphenylalaninemia_due_to_tetrahydrobiopterin_deficiency (1 variants)
• 6-Pyruvoyl-tetrahydrobiopterin_synthase_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the QDPR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000320.3. 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			3	99	1	103
missense	6	20	84	1		111
nonsense	8					8
start loss		1				1
frameshift	8	3				11
splice donor/acceptor (+/-2bp)	4	5	1			10
Total	26	29	88	100	1

Highest pathogenic variant AF is 0.000022586773

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
QDPR	protein_coding	protein_coding	ENST00000281243	7	51974

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000153	0.881	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.285	138	148	0.934	0.00000803	1568
Missense in Polyphen		40	57.128	0.70018		600
Synonymous	0.0988	60	61.0	0.984	0.00000396	499
Loss of Function	1.42	8	13.7	0.585	6.89e-7	139

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases.
• Disease: DISEASE: Hyperphenylalaninemia, BH4-deficient, C (HPABH4C) [MIM:261630]: Rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. Patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated. {ECO:0000269|PubMed:10408783, ECO:0000269|PubMed:11153907, ECO:0000269|PubMed:2116088, ECO:0000269|PubMed:8326489, ECO:0000269|PubMed:9744478}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Folate biosynthesis - Homo sapiens (human);Sepiapterin reductase deficiency;Segawa syndrome;Pterine Biosynthesis;Dopa-responsive dystonia;Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency;Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps);Hyperphenylalaninemia due to dhpr-deficiency;phenylalanine degradation/tyrosine biosynthesis;Folate metabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Phenylalanine and tyrosine catabolism;Metabolism (Consensus)

Recessive Scores

• pRec: 0.403

Intolerance Scores

• loftool: 0.243
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.163
• hipred: N
• hipred_score: 0.495
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.275

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Qdpr
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); skeleton phenotype

Gene ontology

• Biological process: liver development;cellular amino acid metabolic process;L-phenylalanine catabolic process;tetrahydrobiopterin biosynthetic process;response to aluminum ion;response to lead ion;electron transport chain;response to glucagon;cellular response to drug;dihydrobiopterin metabolic process
• Cellular component: cytoplasm;cytosol;neuron projection;extracellular exosome
• Molecular function: 6,7-dihydropteridine reductase activity;electron transfer activity;protein homodimerization activity;NADPH binding;NADH binding