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] See more...

Aliases for SPR Gene

Aliases for SPR Gene

  • Sepiapterin Reductase 2 3 4 5
  • Sepiapterin Reductase (7,8-Dihydrobiopterin:NADP+ Oxidoreductase) 2 3
  • Sepiapterin Reductase (L-Erythro-7,8-Dihydrobiopterin Forming) 2 3
  • Short Chain Dehydrogenase/Reductase Family 38C, Member 1 2 3
  • EC 4 50
  • SDR38C1 2 3
  • SPR 5

External Ids for SPR Gene

Previous GeneCards Identifiers for SPR Gene

  • GC02P073124
  • GC02P073325
  • GC02P073089
  • GC02P073026
  • GC02P072968

Summaries for SPR Gene

Entrez Gene Summary for SPR Gene

  • 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]

GeneCards Summary for SPR Gene

SPR (Sepiapterin Reductase) is a Protein Coding gene. Diseases associated with SPR include Dystonia, Dopa-Responsive, Due To Sepiapterin Reductase Deficiency and Dystonia. Among its related pathways are Metabolism of nitric oxide and Folate biosynthesis. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and aldo-keto reductase (NADP) activity.

UniProtKB/Swiss-Prot Summary for SPR Gene

  • Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.

Gene Wiki entry for SPR Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPR Gene

Genomics for SPR Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SPR Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J072886 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 +0.3 319 2.2 ZNF654 MYC ZNF600 IKZF1 ZMYM3 CEBPA NFIC ZBTB10 YY1 MXD4 SPR lnc-EXOC6B-1 ENSG00000273245 ALMS1 HSALNG0015937 EMX1
GH02J073109 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 10 +224.5 224513 5.2 ZNF600 ZNF592 ZMYM3 ATF2 KLF9 ZNF10 POLR2A ZIC2 CHD4 ZBTB10 RAB11FIP5 ENSG00000272702 ENSG00000273245 SFXN5 ALMS1 DUSP11 EMX1 SPR SMYD5 lnc-SFXN5-2
GH02J073175 Promoter/Enhancer 1.6 FANTOM5 ENCODE CraniofacialAtlas 11.2 +289.5 289516 2.4 EZH2 ZNF654 MYC ZNF600 IKZF1 ZNF580 ZNF592 KLF9 CEBPA BRCA1 ALMS1 SMYD5 SFXN5 ENSG00000273245 RAB11FIP5 PRADC1 NOTO SPR EMX1 CCT7
GH02J073083 Promoter/Enhancer 1.5 Ensembl ENCODE dbSUPER 10.2 +200.4 200424 9.2 ZNF654 SSRP1 JUND ZIC2 CTCF REST TRIM22 THAP11 FOXA2 MAFF lnc-SFXN5-2 piR-54515 RAB11FIP5 SPR SFXN5
GH02J072999 Enhancer 1.1 Ensembl ENCODE 10.8 +113.6 113559 2.3 SSRP1 CEBPA ATF3 CHD4 YY1 MXD4 CHD2 HOMEZ THAP11 KDM6A SFXN5 SPR RAB11FIP5 LOC107985897 piR-36474-003 lnc-SFXN5-1 EMX1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPR on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SPR

Top Transcription factor binding sites by QIAGEN in the SPR gene promoter:
  • C/EBPbeta
  • N-Myc
  • NRSF form 2
  • PPAR-gamma1
  • PPAR-gamma2
  • TBP

Genomic Locations for SPR Gene

Latest Assembly
4,777 bases
Plus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
4,751 bases
Plus strand

(GRCh37/hg19 by Ensembl)
4,799 bases
Plus strand

Genomic View for SPR Gene

Genes around SPR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPR Gene

Proteins for SPR Gene

  • Protein details for SPR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Sepiapterin reductase
    Protein Accession:
    Secondary Accessions:
    • A8K741
    • D6W5H2
    • Q53GI9
    • Q9UBB1

    Protein attributes for SPR Gene

    261 amino acids
    Molecular mass:
    28048 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for SPR Gene

neXtProt entry for SPR Gene

Selected DME Specific Peptides for SPR Gene


Post-translational modifications for SPR Gene

  • In vitro phosphorylation of Ser-213 by CaMK2 does not change kinetic parameters.
  • Ubiquitination at Lys240
  • Modification sites at PhosphoSitePlus

Other Protein References for SPR Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for SPR Gene

Gene Families for SPR Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for SPR Gene

  • Short-chain dehydrogenase/reductase SDR

Suggested Antigen Peptide Sequences for SPR Gene

GenScript: Design optimal peptide antigens:
  • Sepiapterin Reductase (Q9UEC5_HUMAN)
  • Sepiapterin reductase (SPRE_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the sepiapterin reductase family.
  • Belongs to the sepiapterin reductase family.
genes like me logo Genes that share domains with SPR: view

Function for SPR Gene

Molecular function for SPR Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=L-erythro-7,8-dihydrobiopterin + NADP(+) = H(+) + NADPH + sepiapterin; Xref=Rhea:RHEA:18953, ChEBI:CHEBI:15378, ChEBI:CHEBI:16095, ChEBI:CHEBI:43029, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:32627, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:59560, ChEBI:CHEBI:136564; EC=;.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=14.3 uM for sepiapterin {ECO:0000269|PubMed:11825621}; KM=10 uM for NADPH {ECO:0000269|PubMed:11825621};
GENATLAS Biochemistry:
sepiapterin reductase,catalyzing the final step of tetrahydrobiopterin (BH4) synthesis,cofactor for aromatic aminoacid hydroxylase and nitric oxid synthase

Enzyme Numbers (IUBMB) for SPR Gene

Phenotypes From GWAS Catalog for SPR Gene

Gene Ontology (GO) - Molecular Function for SPR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004033 aldo-keto reductase (NADP) activity TAS 1883349
GO:0004757 sepiapterin reductase activity TAS,ISS --
GO:0016491 oxidoreductase activity IEA --
GO:0050661 NADP binding TAS 1883349
genes like me logo Genes that share ontologies with SPR: view
genes like me logo Genes that share phenotypes with SPR: view

Human Phenotype Ontology for SPR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SPR Gene

MGI Knock Outs for SPR:
  • Spr Spr<tm1Lex>
  • Spr Spr<tm1Spo>

Animal Models for research

  • Taconic Biosciences Mouse Models for SPR

miRNA for SPR Gene

miRTarBase miRNAs that target SPR

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPR

No data available for Transcription Factor Targets and HOMER Transcription for SPR Gene

Localization for SPR Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPR Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPR gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 4
mitochondrion 3
plasma membrane 1
cytoskeleton 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SPR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with SPR: view

Pathways & Interactions for SPR Gene

genes like me logo Genes that share pathways with SPR: view

SIGNOR curated interactions for SPR Gene

Other effect:

Gene Ontology (GO) - Biological Process for SPR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006729 tetrahydrobiopterin biosynthetic process IBA,TAS 1883349
GO:0006809 nitric oxide biosynthetic process IDA 15197144
GO:0050999 regulation of nitric-oxide synthase activity TAS --
GO:0055114 oxidation-reduction process TAS --
genes like me logo Genes that share ontologies with SPR: view

Drugs & Compounds for SPR Gene

(14) Drugs for SPR Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tetrahydrobiopterin Approved, Investigational Pharma 0
NADP Experimental Pharma Target 0
n-acetylserotonin Experimental Pharma Target 0
NADPH Experimental Pharma 0
Biopterin Experimental Pharma Target 0

(11) Additional Compounds for SPR Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
1-hydroxy-2-Oxopropyl tetrahydropterin
  • 2-Amino-6-lactoyl-5,6,7,8-tetrahydropteridin-4(3H)-one
  • 6-1'-oxo-2'-Hydroxypropyl tetrahydropterin
  • 6-Lactoyl tetrahydropterin
  • 6-Lactoyl-5,6,7,8-tetrahydropterin
  • Lactoyl-H4-pterin
  • 6-(1,2-Dioxopropyl)-5,6,7,8-tetrahydropterin
  • 6-Pyruvoyl-5,6,7,8-tetrahydropterin
  • 6-Pyruvoyltetrahydropterin
  • 6-Pyruvoyl-tetrahydropterin
  • 6-Pyruvoyl tetrahydropteridine
Hydrogen Ion
  • H+
  • H(+)
  • Hydron
  • Hydrogen cation
  • Proton
genes like me logo Genes that share compounds with SPR: view

Transcripts for SPR Gene

mRNA/cDNA for SPR Gene

6 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPR

Alternative Splicing Database (ASD) splice patterns (SP) for SPR Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c ^ 3a · 3b · 3c
SP2: -
SP3: -

Relevant External Links for SPR Gene

GeneLoc Exon Structure for

Expression for SPR Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SPR Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SPR Gene

This gene is overexpressed in Liver (x4.5).

Protein differential expression in normal tissues from HIPED for SPR Gene

This gene is overexpressed in Bone (29.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SPR Gene

Protein tissue co-expression partners for SPR Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SPR

SOURCE GeneReport for Unigene cluster for SPR Gene:


Evidence on tissue expression from TISSUES for SPR Gene

  • Liver(4.5)
  • Kidney(4.4)
  • Pancreas(4.2)
  • Skin(2.7)
  • Nervous system(2.7)
  • Heart(2.3)
  • Muscle(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SPR Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
  • mouth
  • pharynx
  • skull
  • chest wall
  • heart
  • abdominal wall
  • kidney
  • blood vessel
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with SPR: view

No data available for mRNA Expression by UniProt/SwissProt for SPR Gene

Orthologs for SPR Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SPR Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SPR 29 30
  • 97.7 (n)
(Bos Taurus)
Mammalia SPR 29 30
  • 85.84 (n)
(Canis familiaris)
Mammalia SPR 29 30
  • 85.1 (n)
(Mus musculus)
Mammalia Spr 29 16 30
  • 79.2 (n)
Spr-ps1 30
  • 66 (a)
(Rattus norvegicus)
Mammalia Spr 29
  • 78.72 (n)
(Monodelphis domestica)
Mammalia -- 30
  • 71 (a)
-- 30
  • 68 (a)
-- 30
  • 54 (a)
(Gallus gallus)
Aves SPR 29 30
  • 68.12 (n)
(Anolis carolinensis)
Reptilia SPR 30
  • 65 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia spr 29
  • 60.44 (n)
African clawed frog
(Xenopus laevis)
Amphibia spr-prov 29
(Danio rerio)
Actinopterygii spra 29 30
  • 60.78 (n)
sprb 30
  • 47 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008000 29
  • 50.8 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Sptr 29 30 31
  • 47.2 (n)
CG12116 30
  • 26 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 30
  • 28 (a)
IRC24 30 32
  • 27 (a)
Species where no ortholog for SPR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for SPR Gene

Gene Tree for SPR (if available)
Gene Tree for SPR (if available)
Evolutionary constrained regions (ECRs) for SPR: view image
Alliance of Genome Resources:
Additional Orthologs for SPR

Paralogs for SPR Gene Pseudogenes for SPR Gene

genes like me logo Genes that share paralogs with SPR: view

No data available for Paralogs for SPR Gene

Variants for SPR Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SPR Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
1004405 Uncertain Significance: Dystonia 72,888,538(+) C/G
NM_003124.5(SPR):c.529C>G (p.Arg177Gly)
1014515 Uncertain Significance: Dystonia 72,888,481(+) C/T
NM_003124.5(SPR):c.472C>T (p.Leu158Phe)
1021632 Uncertain Significance: Dystonia 72,891,394(+) G/T
NM_003124.5(SPR):c.643G>T (p.Asp215Tyr)
1026444 Uncertain Significance: Dystonia 72,887,695(+) G/A
NM_003124.5(SPR):c.263G>A (p.Arg88Gln)
1046601 Uncertain Significance: Dystonia 72,887,675(+) C/T
NM_003124.5(SPR):c.243C>T (p.Gly81=)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SPR Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for SPR Gene

Residual Variation Intolerance Score: 41.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.38; 8.46% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPR Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for SPR Gene

Disorders for SPR Gene

MalaCards: The human disease database

(17) MalaCards diseases for SPR Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search SPR in MalaCards View complete list of genes associated with diseases


  • Dystonia, DOPA-responsive, due to sepiapterin reductase deficiency (DRDSPRD) [MIM:612716]: A form of DOPA-responsive dystonia. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. {ECO:0000269 PubMed:11443547, ECO:0000269 PubMed:16650784, ECO:0000269 PubMed:17159114}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for SPR

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with SPR: view

No data available for Genatlas for SPR Gene

Publications for SPR Gene

  1. Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. (PMID: 11443547) Bonafé L … Blau N (American journal of human genetics 2001) 3 4 22 72
  2. Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis. (PMID: 1883349) Ichinose H … Nagatsu T (Biochemical and biophysical research communications 1991) 2 3 4 22
  3. Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia. (PMID: 19491146) Clot F … French Dystonia Network (Brain : a journal of neurology 2009) 3 22 40
  4. Polymorphisms of sepiapterin reductase gene alter promoter activity and may influence risk of bipolar disorder. (PMID: 19415819) McHugh PC … Kennedy MR (Pharmacogenetics and genomics 2009) 3 22 40
  5. The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations. (PMID: 16443856) Sharma M … European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD) (Journal of medical genetics 2006) 3 22 40

Products for SPR Gene

Sources for SPR Gene