QDPR

Chr 4AR

quinoid dihydropteridine reductase

Also known as: DHPR, HDHPR, PKU2, SDR33C1

NCBI Gene: 5860 ENSG00000151552 UniProt: P09417 OMIM: 612676

Dihydropteridine reductase catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin and is an essential component of pterin-dependent aromatic amino acid hydroxylating systems. Autosomal recessive mutations cause BH4-deficient hyperphenylalaninemia, which presents as atypical phenylketonuria due to insufficient biopterin production, a required cofactor for phenylalanine hydroxylase. Pathogenic variants include splicing defects, amino acid substitutions, insertions, and premature terminations that result in enzyme deficiency.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.061 OMIM phenotype

Clinical Summary— QDPR

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Gene-Disease Validity (ClinGen)

dihydropteridine reductase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

64 unique Pathogenic / Likely Pathogenic· 117 VUS of 426 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — QDPR

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.28Z-score

OE missense 0.93 (0.81–1.08)

138 obs / 147.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.34–1.06)

0≤0.351.4

Missense OE?0.93 (0.81–1.08)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 13.7Missense obs/exp: 138 / 147.7Syn Z: 0.10

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveQDPR-related hyperphenylalaninemia, BH4-deficient, CLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7327th %ile

GOF

0.5759th %ile

LOF

0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

426 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic30

VUS117

Likely Benign171

Benign53

Conflicting7

Pathogenic

Likely Pathogenic

117

VUS

171

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	9	5	0	34
Likely Pathogenic	8	21	1	0	30
VUS	1	96	16	4	117
Likely Benign	0	0	75	96	171
Benign	0	0	49	4	53
Conflicting	—				7
Total	29	126	146	104	412

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

View in ClinVar →

45 pathogenic / likely-pathogenic (of 56) ClinVar copy-number / structural variants overlap QDPR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →