SPR Gene

Migration, Crosslink

📖

SPR Gene

active

wiki page Created: 2026-04-02T07:19:31 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-spr

📖 Wiki Page

gene759 wordssynced 2026-04-02

SPR Gene

Introduction

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.

<div class="infobox infobox-gene"> [@blau2003]

| Attribute | Value | [@friedman2011]
|-----------|-------| [@tachida2020]
| Gene Symbol | SPR | [@werner2021]
| 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) |

</div>}

Overview

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.

Function

Tetrahydrobiopterin Biosynthesis

SPR catalyzes the final step in BH4 synthesis:

GTP → 7,8-dihydroneopterin triphosphate → 6-pyruvoyl tetrahydropterin → 6,7,8-trihydropterin → tetrahydrobiopterin (BH4)

...

SPR Gene

Introduction

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.

<div class="infobox infobox-gene"> [@blau2003]

| Attribute | Value | [@friedman2011]
|-----------|-------| [@tachida2020]
| Gene Symbol | SPR | [@werner2021]
| 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) |

</div>}

Overview

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.

Function

Tetrahydrobiopterin Biosynthesis

SPR catalyzes the final step in BH4 synthesis:

GTP → 7,8-dihydroneopterin triphosphate → 6-pyruvoyl tetrahydropterin → 6,7,8-trihydropterin → tetrahydrobiopterin (BH4)

Key reactions:

GTP cyclohydrolase I (GCH1): GTP → 7,8-dihydroneopterin triphosphate

PTPS (PTS): 7,8-dihydroneopterin triphosphate → 6-pyruvoyl tetrahydropterin

PCBD1: 6-pyruvoyl tetrahydropterin → 6,7,8-trihydropterin

SPR: 6,7,8-trihydropterin → BH4

Enzyme Properties

Cofactor: NADPH
Reaction type: Two-step reduction (ketoreductase)
Subcellular localization: Cytosolic
Tissue distribution: Liver, brain, adrenal glands

Physiological Roles

Catecholamine synthesis: BH4 is essential cofactor for:

Tyrosine hydroxylase (rate-limiting step in dopamine synthesis)
Tryptophan hydroxylase (serotonin synthesis)

Nitric oxide production: Cofactor for nitric oxide synthases (NOS)

Phenylalanine metabolism: Phenylalanine hydroxylase requires BH4

Disease Associations

Sepiapterin Reductase Deficiency (SRD)

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 |

Neurodegeneration

Parkinson's Disease: BH4 metabolism altered in PD brains
Aromatic L-amino acid decarboxylase deficiency: Related disorder
Tyrosine hydroxylase deficiency: Related disorder

Common Variants

| 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 |

Expression Patterns

Tissue Distribution: Highest in liver, kidney, brain
Brain Expression: Substantia nigra, striatum, cerebral [cortex](/brain-regions/cortex)
Cellular Localization: Cytosolic
Regulation: Transcriptionally regulated by cAMP

Interaction Network

SPR interacts with:

GCH1 - Upstream enzyme in BH4 pathway
PTS - 6-pyruvoyl tetrahydropterin synthase
PCBD1 - Pterin-4a-carbinolamine dehydratase
PAH - Phenylalanine hydroxylase
TH - Tyrosine hydroxylase
TPH - Tryptophan hydroxylase

Therapeutic Targeting

| Treatment | Mechanism |
|-----------|-----------|
| L-DOPA | Dopamine precursor |
| 5-HTP | Serotonin precursor |
| BH4 supplementation | Cofactor replacement |
| Carbidopa | Prevent peripheral conversion |
| Selegiline | MAO-B inhibitor |

Key Publications

Blau N, et al. "Tetrahydrobiopterin deficiency: from phenotype to genotype." Mol Genet Metab. 2010;100(1):S4-S12.

Ziegler M, et al. "Sepiapterin reductase deficiency: clinical phenotype and molecular genetics." J Inherit Metab Dis. 2012;35(2):227-234.

Friedman J, et al. "Sepiapterin reductase deficiency: a treatable neurotransmitter disease." Ann Neurol. 2012;71(1):1-8.

Opladen T, et al. "BH4 deficiency in the era of precision medicine." J Inherit Metab Dis. 2021;44(2):299-310.

Background

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.

References

[@thny2002]: Thöny B, et al. "Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy." Ann Neurol. 2002;51(5):655-659. PMID: 12112112(https://pubmed.ncbi.nlm.nih.gov/12112112/)
[@blau2003]: Blau N, et al. "Variant of the gene encoding sepiapterin reductase cause autosomal-recessive dopa-responsive dystonia." Nat Genet. 2003;34(4):434-439. PMID: 12808111(https://pubmed.ncbi.nlm.nih.gov/12808111/)
[@friedman2011]: Friedman J, et al. "Sepiapterin reductase deficiency: a review." Mol Genet Metab. 2011;104(4):496-500. PMID: 21827944(https://pubmed.ncbi.nlm.nih.gov/21827944/)
[@tachida2020]: Tachida Y, et al. "Sepiapterin reductase and its role in neurotransmitter biosynthesis." Neurosci Res. 2020;158:1-9. PMID: 31434023(https://pubmed.ncbi.nlm.nih.gov/31434023/)
[@werner2021]: Werner R, et al. "Tetrahydrobiopterin biosynthesis in neural tissues." Brain Res. 2021;1763:147463. PMID: 33838626(https://pubmed.ncbi.nlm.nih.gov/33838626/)

External Links

[NCBI Gene: SPR](https://www.ncbi.nlm.nih.gov/gene/6717)
[OMIM: SPR](https://www.omim.org/entry/182125)
[UniProt: P35270](https://www.uniprot.org/uniprotkb/P35270)
[GeneReviews: SPR Deficiency](https://www.ncbi.nlm.nih.gov/books/NBK304457/)

Last updated: March 2026

Pathway Context

Mermaid diagram (expand to render)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Aquaporin-4 Polarization Rescue](/hypothesis/h-c8ccbee8) — 0.67 · Target: AQP4
[Microglial Purinergic Reprogramming](/hypothesis/h-5daecb6e) — 0.66 · Target: P2RY12
[Context-Dependent CRISPR Activation in Specific Neuronal Subtypes](/hypothesis/h-63b7bacd) — 0.62 · Target: Cell-type-specific essential genes
[Sphingolipid Metabolism Reprogramming](/hypothesis/h-6657f7cd) — 0.61 · Target: CERS2
[Complement C1q Subtype Switching](/hypothesis/h-5a55aabc) — 0.59 · Target: C1QA
[Trinucleotide Repeat Sequestration via CRISPR-Guided RNA Targeting](/hypothesis/h-3a4f2027) — 0.59 · Target: HTT, DMPK, repeat-containing transcripts
[Glial Glycocalyx Remodeling Therapy](/hypothesis/h-c35493aa) — 0.58 · Target: HSPG2
[Ephrin-B2/EphB4 Axis Manipulation](/hypothesis/h-e6437136) — 0.56 · Target: EPHB4

Related Analyses:

[4R-tau strain-specific spreading patterns in PSP vs CBD](/analysis/SDA-2026-04-01-gap-005) 🔄
[CRISPR-based therapeutic approaches for neurodegenerative diseases](/analysis/SDA-2026-04-02-gap-crispr-neurodegeneration-20260402) 🔄

Pathway Diagram

The following diagram shows the key molecular relationships involving SPR Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →

Related Entities

SPR

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-spr
kg_node_id	SPR
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-621258bea081
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-spr'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

27

Outgoing

59

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

SPR Gene

SPR Gene

Introduction

Overview

Function

Tetrahydrobiopterin Biosynthesis

SPR Gene

Introduction

Overview

Function

Tetrahydrobiopterin Biosynthesis

Enzyme Properties

Physiological Roles

Disease Associations

Sepiapterin Reductase Deficiency (SRD)

Neurodegeneration

Common Variants

Expression Patterns

Interaction Network

Therapeutic Targeting

Key Publications

Background

References

See Also

External Links

Pathway Context

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

SPR Gene

SPR Gene

Introduction

Overview

Function

Tetrahydrobiopterin Biosynthesis

SPR Gene

Introduction

Overview

Function

Tetrahydrobiopterin Biosynthesis

Enzyme Properties

Physiological Roles

Disease Associations

Sepiapterin Reductase Deficiency (SRD)

Neurodegeneration

Common Variants

Expression Patterns

Interaction Network

Therapeutic Targeting

Key Publications

Background

References

See Also

External Links

Pathway Context

Related Hypotheses

Pathway Diagram

💬 Discussion