SPR

Chr 2ADAR

sepiapterin reductase

Also known as: SDR38C1

The protein catalyzes the final reductions in tetrahydrobiopterin (BH4) biosynthesis through NADPH-dependent reduction of pteridine derivatives. Mutations cause dopa-responsive dystonia due to sepiapterin reductase deficiency, which can be inherited in either autosomal recessive or autosomal dominant patterns. The pathogenic mechanism involves deficient BH4 production, leading to impaired neurotransmitter synthesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 1.141 OMIM phenotype
Clinical SummarySPR
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.14LOEUF
pLI 0.043
Z-score 1.35
OE 0.44 (0.201.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.73Z-score
OE missense 0.81 (0.690.96)
100 obs / 122.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.201.14)
00.351.4
Missense OE0.81 (0.690.96)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 3 / 6.8Missense obs/exp: 100 / 122.8Syn Z: 1.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSPR-related DOPA-responsive dystonia due to sepiapterin reductase deficiencyLOFAR

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

DN
0.7230th %ile
GOF
0.5563th %ile
LOF
0.2483th %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.

Literature Evidence

LOFThe findings indicate that haploinsufficiency of SPR can be a rare cause of DRD.PMID:15241655

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Trapezoidal prism-coupled SPR.
Zhang F et al.·Appl Opt
2025
Developments in SPR Fragment Screening.
Chavanieu A et al.·Expert Opin Drug Discov
2016Review
Top 5 results · since 2015Search PubMed ↗