Spr Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
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| Attribute | Value |
|---|---|
| Gene Symbol | SPR |
| Gene Name | Sepiapterin Reductase |
| Official Full Name | Sepiapterin Reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase) |
| Chromosomal Location | 2p14 |
| GRCh38 Coordinates | chr2:73,016,252-73,029,687 |
| NCBI Gene ID | 6717 |
| OMIM ID | 182125 |
| Ensembl ID | ENSG00000166347 |
| UniProt ID | P35270 |
| Gene Family | Short-chain dehydrogenases/reductases (SDR) |
The SPR gene encodes Sepiapterin Reductase (SPR), the final enzyme in the tetrahydrobiopterin (BH4) biosynthesis pathway.[1] BH4 is an essential cofactor for aromatic amino acid hydroxylases (phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase) and nitric oxide synthases. SPR deficiency causes a rare neurological disorder characterized by dopa-responsive dystonia and neurological deterioration.
SPR catalyzes the final step in BH4 synthesis:
GTP → 7,8-dihydroneopterin triphosphate → 6-pyruvoyl tetrahydropterin → 6,7,8-trihydropterin → tetrahydrobiopterin (BH4)
Key reactions:
Catecholamine synthesis: BH4 is essential cofactor for:
Nitric oxide production: Cofactor for nitric oxide synthases (NOS)
Phenylalanine metabolism: Phenylalanine hydroxylase requires BH4
A rare autosomal recessive disorder causing:[2]
| Feature | Description |
|---|---|
| Dystonia | Dopa-responsive, diurnal fluctuation |
| Parkinsonism | Bradykinesia, rigidity |
| Developmental delay | Intellectual disability |
| Hypotonia | Infantile-onset |
| Seizures | May occur |
| Diurnal fluctuation | Symptoms worsen throughout day |
| Variant | Effect | Clinical Significance |
|---|---|---|
| c.613G>A (p.G205S) | Missense | Common pathogenic variant |
| c.596A>G (p.Y199C) | Missense | Recurrent mutation |
| c.512T>C (p.L171P) | Missense | Severe phenotype |
| c. 613G>A / c.596A>G | Compound het | Most common genotype |
SPR interacts with:
| Treatment | Mechanism |
|---|---|
| L-DOPA | Dopamine precursor |
| 5-HTP | Serotonin precursor |
| BH4 supplementation | Cofactor replacement |
| Carbidopa | Prevent peripheral conversion |
| Selegiline | MAO-B inhibitor |
The study of Spr Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Last updated: March 2026