SPR

Chr 2ADAR

sepiapterin reductase

Also known as: SDR38C1

NCBI Gene: 6697ENSG00000116096UniProt: P35270

This gene encodes an aldo-keto reductase that catalyzes the NADPH-dependent reduction of pteridine derivatives and is important in the biosynthesis of tetrahydrobiopterin (BH4). Mutations in this gene result in DOPA-responsive dystonia due to sepiaterin reductase deficiency. A pseudogene has been identified on chromosome 1. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Dystonia, dopa-responsive, due to sepiapterin reductase deficiencyMIM #612716
ADAR
294
ClinVar variants
49
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— SPR
🧬
Gene-Disease Validity (ClinGen)
dopa-responsive dystonia due to sepiapterin reductase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 Pathogenic / Likely Pathogenic· 110 VUS of 294 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.
1.14LOEUF
pLI 0.043
Z-score 1.35
OE 0.44 (0.20–1.14)
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.
0.73Z-score
OE missense 0.81 (0.69–0.96)
100 obs / 122.8 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.0.44 (0.20–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.69–0.96)
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.0.81
0≤1.21.6
LoF obs/exp: 3 / 6.8Missense obs/exp: 100 / 122.8Syn Z: 1.17

ClinVar Variant Classifications

294 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic16
VUS110
Likely Benign113
Benign8
Conflicting14
33
Pathogenic
16
Likely Pathogenic
110
VUS
113
Likely Benign
8
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
5
20
0
33
Likely Pathogenic
6
4
6
0
16
VUS
0
89
20
1
110
Likely Benign
0
0
21
92
113
Benign
0
0
7
1
8
Conflicting
—14
Total14987494294

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

View in ClinVar →

Protein Context — Lollipop Plot

SPR · protein map & ClinVar variants

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

Gene2Phenotype Curations

SPR-related DOPA-responsive dystonia due to sepiapterin reductase deficiency

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

Dystonia, dopa-responsive, due to sepiapterin reductase deficiency

MIM #612716

Molecular basis of disorder known

?Autosomal dominantAutosomal recessive
📖
GeneReview available — SPR
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
Pérez-Dueñas B et al.·Mov Disord
2022
U.S. Selected Practice Recommendations for Contraceptive Use, 2024.
Curtis KM et al.·MMWR Recomm Rep
2024Guideline
Dystonia-plus syndromes.
Asmus F et al.·Eur J Neurol
2010Review
Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review.
Weissbach A et al.·Mov Disord
2022Review
CT urography.
Kawashima A et al.·Radiographics
2004Review
Galangin alleviates vitiligo by targeting ANXA2 degradation in macrophages.
Wei W et al.·Br J Pharmacol
2025
Molecular and metabolic bases of tetrahydrobiopterin (BH(4)) deficiencies.
Himmelreich N et al.·Mol Genet Metab
2021Review
Bacteriophages: biosensing tools for multi-drug resistant pathogens.
Tawil N et al.·Analyst
2014Review
Surface plasmon resonance applications in clinical analysis.
Mariani S et al.·Anal Bioanal Chem
2014Review
Fei Wei formula attenuates pulmonary fibrosis by inhibiting lactate-driven endothelial mesenchymal transition via its target of HSP90ab1.
Gu JM et al.·Phytomedicine
2025
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