SPR (Sepiapterin Reductase) Gene

Key enzyme in tetrahydrobiopterin (BH4) biosynthesis and recycling; associated with dopa-responsive dystonia and hyperphenylalaninemia.

Gene Information Card

Symbol SPR
Full Name sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)
Gene Type protein-coding
Chromosomal Location 2p13.2
NCBI Gene ID 6697 ncbi.nlm.nih.gov/gene/6697
Ensembl ID ENSG00000116096
UniProt ID P35270
OMIM ID 182125
HGNC ID 11257
Aliases SDR38C1, SPR, sepiapterin reductase

Description

The SPR gene encodes sepiapterin reductase, an enzyme that catalyzes the final step in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for aromatic amino acid hydroxylases (phenylalanine, tyrosine, and tryptophan hydroxylases) and nitric oxide synthases. Mutations in SPR cause sepiapterin reductase deficiency (SRD), a rare autosomal recessive disorder characterized by dopa-responsive dystonia, hyperphenylalaninemia, and neurotransmitter imbalances.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Dopa-responsive dystonia (DRD) due to sepiapterin reductase deficiency Loss-of-function mutations in SPR impair BH4 synthesis, reducing dopamine and serotonin production OMIM #612716; multiple case reports and functional studies
Hyperphenylalaninemia (mild) Reduced BH4 leads to decreased phenylalanine hydroxylase activity ClinVar; biochemical evidence

Expression Profile

Tissue Expression
Tissue nTPM level
Liver 12.5 Medium
Brain (cerebellum) 8.2 Medium
Kidney 7.1 Medium
Adrenal gland 6.8 Medium
Testis 4.3 Low
Cell Line Expression
Cell Line nTPM Notes
HepG2 10.1 Hepatocyte line
SH-SY5Y 7.8 Neuroblastoma line
HEK293 6.5 Embryonic kidney line
K562 3.2 Leukemia line
Data source：Human Protein Atlas（proteinatlas.org）

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.448A>G (p.Lys150Glu) Missense Rare Reduced enzyme activity
c.586C>T (p.Arg196Trp) Missense Rare Impaired BH4 binding
c.751G>A (p.Gly251Arg) Missense Rare Loss of function
c.1A>G (p.Met1Val) Start loss Rare No protein production
Mutation functional classification

Loss of Function (LOF)

Most SPR mutations are loss-of-function, reducing or abolishing sepiapterin reductase activity, leading to BH4 deficiency.

Gain of Function (GOF)

No gain-of-function mutations reported.

Dominant Negative (DN)

No dominant-negative effects described; inheritance is autosomal recessive.
View complete mutation data：
ClinVar：https://www.clinvar.com/gene/6697
COSMIC：https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=SPR

Gene Ontology (GO)

• sepiapterin reductase activity (GO:0004757) • tetrahydrobiopterin biosynthetic process (GO:0006729)
• cytosol (GO:0005829) • cytoplasm (GO:0005737)
• NADP binding (GO:0050661)

Pathways

• Tetrahydrobiopterin (BH4) biosynthesis and recycling (Reactome: R-HSA-1474151)
• Metabolism of cofactors and vitamins (KEGG: hsa00790)

Protein Summary

Sepiapterin reductase (SPR) is a 261-amino acid enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family. It catalyzes the NADPH-dependent reduction of 6-pyruvoyltetrahydropterin to tetrahydrobiopterin (BH4). The protein is homodimeric and expressed in various tissues, with highest levels in liver and brain. Defects in SPR cause BH4 deficiency, leading to impaired neurotransmitter synthesis and neurological symptoms.

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Related Products

Product name Cat.No. Species Gene ID
SPRED2 Knockout HEK293 Cell Line EDJ-KQ4588 Human 200734 Details Get a Quote
SPR Knockout HEK293 Cell Line EDJ-KQ5086 Human 6697 Details Get a Quote
SPRY1 Knockout HEK293 Cell Line EDJ-KQ6975 Human 10252 Details Get a Quote
SPRY2 Knockout HEK293 Cell Line EDJ-KQ6978 Human 10253 Details Get a Quote
SPRY4 Knockout HEK293 Cell Line EDJ-KQ9755 Human 81848 Details Get a Quote
SPRYD3 Knockout HEK293 Cell Line EDJ-KQ10262 Human 84926 Details Get a Quote
RSPRY1 Knockout HEK293 Cell Line EDJ-KQ10543 Human 89970 Details Get a Quote
ASPRV1 Knockout HEK293 Cell Line EDJ-KQ11340 Human 151516 Details Get a Quote
SPRING1 Knockout HEK293 Cell Line EDJ-KQ11920 Human 79794 Details Get a Quote
BSPRY Knockout HEK293 Cell Line EDJ-KQ12572 Human 54836 Details Get a Quote
SPRED1 Knockout HEK293 Cell Line EDJ-KQ15493 Human 161742 Details Get a Quote
SPRED3 Knockout HEK293 Cell Line EDJ-KQ15494 Human 399473 Details Get a Quote
SPRN Knockout HEK293 Cell Line EDJ-KQ15495 Human 503542 Details Get a Quote
SPRR5 Knockout HEK293 Cell Line EDJ-KQ15496 Human 110806278 Details Get a Quote
SPRYD4 Knockout HEK293 Cell Line EDJ-KQ15497 Human 283377 Details Get a Quote
Displaying Records 1 To 15 Of 108 Records

Reference Databases

NCBI Gene https://www.ncbi.nlm.nih.gov/gene/6697
OMIM https://www.omim.org/entry/182125
HGNC https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11257
Ensembl https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000116096
UniProt https://www.uniprot.org/uniprot/P35270
ClinVar https://www.ncbi.nlm.nih.gov/clinvar/?term=SPR%5Bgene%5D
COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=SPR
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