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…

Primary Disease Associations & Inheritance

Hyperphenylalaninemia, BH4-deficient, CMIM #261630

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · dihydropteridine reductase deficiency · AR · ClinGen 2018

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in QDPR?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

361 rare PASS variants

Rare truncating (LoF)

1 in 3,600

49 rare PASS variants

Rare synonymous (reference)

1 in 310

115 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for QDPR. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 3,700
South Asian	~43k	1 in 160	1 in 6,100
Remaining (unassigned)	~30k	1 in 170	1 in 740
European (Finnish)	~27k	1 in 290	≈ 1 in 8,900
Admixed American	~22k	1 in 260	≈ 1 in 4,500
African / African American	~21k	1 in 200	1 in 3,300
East Asian	~20k	1 in 150	1 in 1,200
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 160	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓