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 1.1.1.153 4 51
  • 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 and eNOS activation and regulation. 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
- 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

Genomic Locations for SPR Gene
chr2:72,887,382-72,892,158
(GRCh38/hg38)
Size:
4,777 bases
Orientation:
Plus strand
chr2:73,114,489-73,119,289
(GRCh37/hg19)
Size:
4,801 bases
Orientation:
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:
    P35270-SPRE_HUMAN
    Recommended name:
    Sepiapterin reductase
    Protein Accession:
    P35270
    Secondary Accessions:
    • A8K741
    • D6W5H2
    • Q53GI9
    • Q9UBB1

    Protein attributes for SPR Gene

    Size:
    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

P35270:
  • SGAHVDFYD
  • MQQLARETS

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

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

Protein Domains for SPR Gene

InterPro:
Blocks:
  • Short-chain dehydrogenase/reductase SDR
ProtoNet:

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

P35270

UniProtKB/Swiss-Prot:

SPRE_HUMAN :
  • Belongs to the sepiapterin reductase family.
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=1.1.1.153;.
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=1.1.1.153;.
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 Model Products

  • Taconic Biosciences Mouse Models for SPR

CRISPR Products

miRNA for SPR Gene

miRTarBase miRNAs that target SPR

Inhibitory RNA Products

  • 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

Cytoplasm.

Subcellular locations from

COMPARTMENTS
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:0051186 cofactor metabolic process TAS --
GO:0055114 oxidation-reduction process TAS 1883349
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
Sapropterin Approved, Investigational Pharma 0
NADP Experimental Pharma Target 0
n-acetylserotonin Experimental Pharma Target 0
NADPH Experimental Pharma 0
Biopterin Experimental Pharma Target 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Sepiapterin
  • (S)-2-amino-7,8-dihydro-6-(2-Hydroxy-1-oxopropyl)-4(1H)-pteridinone
  • 1-(2-amino-7,8-dihydro-4-Hydroxy-6-pteridinyl)-2-hydroxy-1-propanone
  • 2-amino-6-(S)-Lactoyl-7,8-dihydro-4(3H)-pteridinone
  • 2-amino-7,8-dihydro-6-[(2S)-2-Hydroxy-1-oxopropyl]-4(1H)pteridinone
  • L-Sepiapterin
17094-01-8
1-hydroxy-2-Oxopropyl tetrahydropterin
6-Lactoyltetrahydropterin
  • 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
33405-80-0
Dyspropterin
  • 6-(1,2-Dioxopropyl)-5,6,7,8-tetrahydropterin
  • 6-Pyruvoyl-5,6,7,8-tetrahydropterin
  • 6-Pyruvoyltetrahydropterin
  • 6-Pyruvoyl-tetrahydropterin
  • 6-Pyruvoyl tetrahydropteridine
89687-39-8
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
genes like me logo Genes that share compounds with SPR: view

Transcripts for SPR Gene

mRNA/cDNA for SPR Gene

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

CRISPR Products

Inhibitory RNA Products

  • 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
SP1:
SP2: -
SP3: -

Relevant External Links for SPR Gene

GeneLoc Exon Structure for
SPR

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:

Hs.301540

Evidence on tissue expression from TISSUES for SPR Gene

  • Liver(4.5)
  • Kidney(4.4)
  • Pancreas(4.2)
  • Nervous system(2.8)
  • Skin(2.8)
  • Heart(2.5)
  • Muscle(2.3)
  • Adrenal gland(2.1)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
  • mouth
  • pharynx
  • skull
Thorax:
  • chest wall
  • heart
Abdomen:
  • abdominal wall
  • kidney
General:
  • 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
Chimpanzee
(Pan troglodytes)
Mammalia SPR 30 31
  • 97.7 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SPR 30 31
  • 85.84 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SPR 30 31
  • 85.1 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Spr 30 17 31
  • 79.2 (n)
OneToMany
Spr-ps1 31
  • 66 (a)
OneToMany
Rat
(Rattus norvegicus)
Mammalia Spr 30
  • 78.72 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 71 (a)
OneToMany
-- 31
  • 68 (a)
OneToMany
-- 31
  • 54 (a)
OneToMany
Chicken
(Gallus gallus)
Aves SPR 30 31
  • 68.12 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SPR 31
  • 65 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia spr 30
  • 60.44 (n)
African clawed frog
(Xenopus laevis)
Amphibia spr-prov 30
Zebrafish
(Danio rerio)
Actinopterygii spra 30 31
  • 60.78 (n)
OneToMany
sprb 31
  • 47 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008000 30
  • 50.8 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Sptr 30 31 32
  • 47.2 (n)
OneToMany
CG12116 31
  • 26 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 31
  • 28 (a)
OneToMany
IRC24 31 33
  • 27 (a)
OneToMany
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

ENSEMBL:
Gene Tree for SPR (if available)
TreeFam:
Gene Tree for SPR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPR: view image

Paralogs for SPR Gene

Pseudogenes.org 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
625209 Pathogenic: Intellectual disability; Dystonia 72,888,312(+) A/G SPLICE_ACCEPTOR_VARIANT
642591 Uncertain Significance: Dystonia 72,888,604(+) G/C MISSENSE_VARIANT
642830 Uncertain Significance: Dystonia 72,888,445(+) C/A MISSENSE_VARIANT
643639 Uncertain Significance: Dystonia 72,887,715(+) C/G MISSENSE_VARIANT
646415 Uncertain Significance: Dystonia 72,887,448(+) G/C MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for SPR Gene

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)
SPR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPR

SNP Genotyping and Copy Number Assay Products

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

(14) MalaCards diseases for SPR Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

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

UniProtKB/Swiss-Prot

SPRE_HUMAN
  • 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 mutations affecting the gene represented in this entry.

Additional Disease Information for SPR

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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. 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 23
  2. 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 23 41
  3. 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 23 41
  4. 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 23 41
  5. Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II. (PMID: 11825621) Fujimoto K … Katoh S (Biochimica et biophysica acta 2002) 3 4 23

Products for SPR Gene

Sources for SPR Gene