QDPR

Chr 4AR

quinoid dihydropteridine reductase

Also known as: DHPR, HDHPR, PKU2, SDR33C1

NCBI Gene: 5860ENSG00000151552UniProt: P09417

This gene encodes the enzyme dihydropteridine reductase, which catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin. This enzyme is an essential component of the pterin-dependent aromatic amino acid hydroxylating systems. Mutations in this gene resulting in QDPR deficiency include aberrant splicing, amino acid substitutions, insertions, or premature terminations. Dihydropteridine reductase deficiency presents as atypical phenylketonuria due to insufficient production of biopterin, a cofactor for phenylalanine hydroxylase. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Hyperphenylalaninemia, BH4-deficient, CMIM #261630
AR
466
ClinVar variants
108
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— QDPR
🧬
Gene-Disease Validity (ClinGen)
dihydropteridine reductase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
108 Pathogenic / Likely Pathogenic· 125 VUS of 466 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.06LOEUF
pLI 0.000
Z-score 1.42
OE 0.59 (0.34–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.28Z-score
OE missense 0.93 (0.81–1.08)
138 obs / 147.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.34–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.81–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 8 / 13.7Missense obs/exp: 138 / 147.7Syn Z: 0.10

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic31
VUS125
Likely Benign173
Benign53
Conflicting7
77
Pathogenic
31
Likely Pathogenic
125
VUS
173
Likely Benign
53
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
8
57
0
77
Likely Pathogenic
8
21
2
0
31
VUS
1
90
30
4
125
Likely Benign
0
0
77
96
173
Benign
0
0
49
4
53
Conflicting
—7
Total21119215104466

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

QDPR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

QDPR-related hyperphenylalaninemia, BH4-deficient, C

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperphenylalaninemia, BH4-deficient, C

MIM #261630

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Effects of oral sepiapterin on blood Phe concentration in a broad range of patients with phenylketonuria (APHENITY): results of an international, phase 3, randomised, double-blind, placebo-controlled trial.
Muntau AC et al.·Lancet
2024Clinical trial
Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review.
Weissbach A et al.·Mov Disord
2022Review
A Comprehensive Study of Disease-Causing Variants in PAH, QDPR, PTS, and PCD Genes in Iranian Patients with Hyperphenylalaninemia: A Systematic Review.
Ghanei M et al.·Hum Hered
2023Meta-analysis
QDPR gene mutation and clinical follow-up in Chinese patients with dihydropteridine reductase deficiency.
Lu DY et al.·World J Pediatr
2014Cohort
Multi-omics insight into the molecular networks of mental disorder related genetic pathways in the pathogenesis of inflammatory bowel disease.
Zhang M et al.·Transl Psychiatry
2025
Molecular and metabolic bases of tetrahydrobiopterin (BH(4)) deficiencies.
Himmelreich N et al.·Mol Genet Metab
2021Review
Comprehensive bioinformatics analysis of structural and functional consequences of deleterious missense mutations in the human QDPR gene.
Girish A et al.·J Biomol Struct Dyn
2024Functional
Genome sequencing identifies a homozygous inversion disrupting QDPR as a cause for dihydropteridine reductase deficiency.
Lilleväli H et al.·Mol Genet Genomic Med
2020Case report
Proteome profiling identifies circulating biomarkers associated with hepatic steatosis in subjects with Prader-Willi syndrome.
Pascut D et al.·Front Endocrinol (Lausanne)
2023
Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.
Sadat Fatemi SH et al.·Mol Genet Genomic Med
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools