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Aliases for GCH1 Gene

Aliases for GCH1 Gene

  • GTP Cyclohydrolase 1 2 3
  • DYT5 3 4 6
  • GTP Cyclohydrolase I 3 4
  • Dystonia 14 2 3
  • EC 3.5.4.16 4 64
  • GTP-CH-I 3 4
  • HPABH4B 3 6
  • GCH 3 4
  • Guanosine 5-Triphosphate Cyclohydrolase I 3
  • Dopa-Responsive Dystonia 2
  • GTP-CH-1 3
  • GTPCH1 3
  • DYT5a 3
  • DYT14 3

External Ids for GCH1 Gene

Previous Symbols for GCH1 Gene

  • GCH
  • DYT5
  • DYT14

Summaries for GCH1 Gene

Entrez Gene Summary for GCH1 Gene

  • This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]

GeneCards Summary for GCH1 Gene

GCH1 (GTP Cyclohydrolase 1) is a Protein Coding gene. Diseases associated with GCH1 include gtp cyclohydrolase 1-deficient dopa-responsive dystonia and oromandibular dystonia. Among its related pathways are Metabolism and Metabolism. GO annotations related to this gene include calcium ion binding and GTP binding.

UniProtKB/Swiss-Prot for GCH1 Gene

  • Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.

Gene Wiki entry for GCH1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GCH1 Gene

Genomics for GCH1 Gene

Genomic Location for GCH1 Gene

Start:
54,842,005 bp from pter
End:
54,902,885 bp from pter
Size:
60,881 bases
Orientation:
Minus strand

Genomic View for GCH1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for GCH1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GCH1 Gene

Regulatory Elements for GCH1 Gene

Proteins for GCH1 Gene

  • Protein details for GCH1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P30793-GCH1_HUMAN
    Recommended name:
    GTP cyclohydrolase 1
    Protein Accession:
    P30793
    Secondary Accessions:
    • Q6FHY7
    • Q9Y4I8

    Protein attributes for GCH1 Gene

    Size:
    250 amino acids
    Molecular mass:
    27903 Da
    Quaternary structure:
    • Toroid-shaped homodecamer, composed of a dimer of pentamers. The inactive isoforms also form decamers and may possibly be incorporated into GCH1 heterodecamers, decreasing enzyme stability and activity. Interacts with AHSA1 and GCHFR/GFRP.

    Three dimensional structures from OCA and Proteopedia for GCH1 Gene

    Alternative splice isoforms for GCH1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GCH1 Gene

Proteomics data for GCH1 Gene at MOPED

Selected DME Specific Peptides for GCH1 Gene

Post-translational modifications for GCH1 Gene

  • Phosphorylated by casein kinase II at Ser-81 in HAECs during oscillatory shear stress; phosphorylation at Ser-81 results in increased enzyme activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GCH1 Gene

Domains for GCH1 Gene

Protein Domains for GCH1 Gene

UniProtKB/Swiss-Prot:

GCH1_HUMAN
Family:
  • Belongs to the GTP cyclohydrolase I family.:
    • P30793
genes like me logo Genes that share domains with GCH1: view

No data available for Gene Families for GCH1 Gene

Function for GCH1 Gene

Molecular function for GCH1 Gene

GENATLAS Biochemistry: GTP cyclohydrolase I,catalyzing the first step of tetrahydrobiopterin (BH4) synthesis
UniProtKB/Swiss-Prot BiophysicochemicalProperties: Kinetic parameters: KM=116 uM for GTP {ECO:0000269 PubMed:2500984}; pH dependence: Optimum pH is 7.7 in phosphate buffer. {ECO:0000269 PubMed:2500984}; Temperature dependence: Relatively stable at high temperatures. Retains 50% of its activity after incubation at 70 degrees Celsius for 15 minutes. {ECO:0000269 PubMed:2500984};
UniProtKB/Swiss-Prot CatalyticActivity: GTP + H(2)O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate.
UniProtKB/Swiss-Prot EnzymeRegulation: GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg(2+).
UniProtKB/Swiss-Prot Function: Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.
UniProtKB/Swiss-Prot Induction: Up-regulated by IFNG/IFN-gamma, TNF, IL1B/interleukin-1 beta, bacterial lipopolysaccharides (LPS) and phenylalanine, and down-regulated by dibutyryl-cAMP, iloprost and 8-bromo-cGMP in HUVEC cells. Up-regulation of GCH1 expression, in turn, stimulates production of tetrahydrobiopterin, with subsequent elevation of endothelial nitric oxide synthase activity. Cytokine-induced GCH1 up-regulation in HUVECs in response to TNF and IFNG/IFN-gamma involves cooperative activation of both the NF-kappa-B and JAK2/STAT pathways. Also up-regulated by hydrogen peroxide in human aorta endothelial cells (HAECs).

Enzyme Numbers (IUBMB) for GCH1 Gene

Gene Ontology (GO) - Molecular Function for GCH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003934 NOT GTP cyclohydrolase I activity IDA 11284739
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 16696853
GO:0005525 GTP binding IDA 14717702
GO:0008270 zinc ion binding IDA 11087823
genes like me logo Genes that share ontologies with GCH1: view

Phenotypes for GCH1 Gene

GenomeRNAi human phenotypes for GCH1:
genes like me logo Genes that share phenotypes with GCH1: view

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for GCH1 Gene

Localization for GCH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GCH1 Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for GCH1 Gene COMPARTMENTS Subcellular localization image for GCH1 gene
Compartment Confidence
cytosol 5
nucleus 5
extracellular 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for GCH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 16778797
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0031410 cytoplasmic vesicle IDA 3318829
genes like me logo Genes that share ontologies with GCH1: view

Pathways for GCH1 Gene

genes like me logo Genes that share pathways with GCH1: view

UniProtKB/Swiss-Prot P30793-GCH1_HUMAN

  • Pathway: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1

Gene Ontology (GO) - Biological Process for GCH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006184 obsolete GTP catabolic process --
GO:0006461 protein complex assembly --
GO:0006729 tetrahydrobiopterin biosynthetic process IMP 17101830
GO:0006809 nitric oxide biosynthetic process NAS 9445252
GO:0008152 metabolic process IDA 3753653
genes like me logo Genes that share ontologies with GCH1: view

Compounds for GCH1 Gene

(8) HMDB Compounds for GCH1 Gene

Compound Synonyms Cas Number PubMed IDs
2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine
Not Available
2,5-Diaminopyrimidine nucleoside triphosphate
Not Available
Dihydroneopterin triphosphate
  • 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl) dihydropteridine triphosphate
20574-65-6
Formamidopyrimidine nucleoside triphosphate
Not Available
Formic acid
  • Add-F
64-18-6

(1) Drugbank Compounds for GCH1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Guanine
73-40-5 target inhibitor

(46) Novoseek inferred chemical compound relationships for GCH1 Gene

Compound -log(P) Hits PubMed IDs
tetrahydrobiopterin 96.8 102
gtp 94.1 229
sepiapterin 92.3 19
6-pyruvoyltetrahydropterin 90.9 17
2,4-diamino-6-hydroxypyrimidine 87.7 5
genes like me logo Genes that share compounds with GCH1: view

Transcripts for GCH1 Gene

Unigene Clusters for GCH1 Gene

GTP cyclohydrolase 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for GCH1 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9
SP1: - -
SP2: -
SP3: - - -
SP4:

Relevant External Links for GCH1 Gene

GeneLoc Exon Structure for
GCH1
ECgene alternative splicing isoforms for
GCH1

Expression for GCH1 Gene

mRNA expression in normal human tissues for GCH1 Gene

mRNA differential expression in normal tissues according to GTEx for GCH1 Gene

This gene is overexpressed in Liver (11.5).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for GCH1 Gene

SOURCE GeneReport for Unigene cluster for GCH1 Gene Hs.86724

mRNA Expression by UniProt/SwissProt for GCH1 Gene

P30793-GCH1_HUMAN
Tissue specificity: In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but not all melanocytes (at protein level).
genes like me logo Genes that share expressions with GCH1: view

Orthologs for GCH1 Gene

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

Orthologs for GCH1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GCH1 36
  • 99.87 (n)
  • 100 (a)
GCH1 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GCH1 36
  • 89.96 (n)
  • 91.57 (a)
GCH1 37
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia GCH1 36
  • 93.71 (n)
  • 96.79 (a)
GCH1 37
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Gch1 36
  • 88.19 (n)
  • 89.17 (a)
Gch1 16
Gch1 37
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GCH1 37
  • 58 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GCH1 37
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gch1 36
  • 90.28 (n)
  • 92.5 (a)
chicken
(Gallus gallus)
Aves GCH1 36
  • 81.97 (n)
  • 84.55 (a)
GCH1 37
  • 82 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GCH1 37
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gch1 36
  • 73.61 (n)
  • 80 (a)
Str.6098 36
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11719 36
zebrafish
(Danio rerio)
Actinopterygii gch 36
gch1 36
  • 78.17 (n)
  • 88 (a)
gch1 37
  • 71 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006441 36
  • 65.79 (n)
  • 74.35 (a)
fruit fly
(Drosophila melanogaster)
Insecta Pu 36
  • 69.03 (n)
  • 76.5 (a)
Pu 37
  • 47 (a)
OneToOne
Pu 38
  • 75 (a)
worm
(Caenorhabditis elegans)
Secernentea cat-4 36
  • 65.4 (n)
  • 71.74 (a)
cat-4 37
  • 60 (a)
OneToOne
F32G8.6 38
  • 71 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGR335C 36
  • 59.1 (n)
  • 60.7 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FOL2 36
  • 56.62 (n)
  • 59.33 (a)
FOL2 37
  • 51 (a)
OneToOne
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A09735g 36
  • 59.28 (n)
  • 65.98 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU07774 36
  • 61.61 (n)
  • 61.24 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPAC17A5.13 36
  • 56.47 (n)
  • 58.9 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.7353 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 70 (a)
OneToOne
Species with no ortholog for GCH1:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)

Evolution for GCH1 Gene

ENSEMBL:
Gene Tree for GCH1 (if available)
TreeFam:
Gene Tree for GCH1 (if available)

Paralogs for GCH1 Gene

No data available for Paralogs for GCH1 Gene

Variants for GCH1 Gene

Sequence variations from dbSNP and Humsavar for GCH1 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type MAF
rs841 -- 54,843,774(-) AAGTA(C/T)GTGCA utr-variant-3-prime, intron-variant
rs987 -- 54,843,776(-) GTAAG(C/T)ACGTG utr-variant-3-prime, intron-variant
rs752688 -- 54,844,851(+) GAAAT(C/T)AAGAG intron-variant
rs998259 -- 54,888,313(+) GTGAG(C/T)GATGA intron-variant
rs1753589 -- 54,902,784(-) CAGGT(C/T)GCGTA utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for GCH1 Gene

Variant ID Type Subtype PubMed ID
nsv819735 CNV Loss 19587683
esv2675781 CNV Deletion 23128226
esv2659466 CNV Deletion 23128226
esv2661782 CNV Deletion 23128226

Relevant External Links for GCH1 Gene

HapMap Linkage Disequilibrium report
GCH1
Human Gene Mutation Database (HGMD)
GCH1
Locus Specific Mutation Databases (LSDB)
GCH1

Disorders for GCH1 Gene

(2) OMIM Diseases for GCH1 Gene (600225)

UniProtKB/Swiss-Prot

GCH1_HUMAN
  • Hyperphenylalaninemia, BH4-deficient, B (HPABH4B) [MIM:233910]: A disease characterized by malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency, and defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia. In this intermediate phenotype, there is marked motor delay, but no mental retardation and only minimal, if any, hyperphenylalaninemia. {ECO:0000269 PubMed:7501255, ECO:0000269 PubMed:9667588}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Dystonia, dopa-responsive (DRD) [MIM:128230]: A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise. {ECO:0000269 PubMed:10076897, ECO:0000269 PubMed:10208576, ECO:0000269 PubMed:10582612, ECO:0000269 PubMed:10825351, ECO:0000269 PubMed:10987649, ECO:0000269 PubMed:11113234, ECO:0000269 PubMed:12391354, ECO:0000269 PubMed:17101830, ECO:0000269 PubMed:7501255, ECO:0000269 PubMed:7874165, ECO:0000269 PubMed:8852666, ECO:0000269 PubMed:8957022, ECO:0000269 PubMed:9120469, ECO:0000269 PubMed:9328244, ECO:0000269 PubMed:9778264}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(22) Novoseek inferred disease relationships for GCH1 Gene

Disease -log(P) Hits PubMed IDs
gtp cyclohydrolase i deficiency 96.1 18
dystonia 5 89 4
hyperphenylalaninemia 85.1 9
dystonia hereditary 73.9 1
torsion dystonia 73.5 6

Relevant External Links for GCH1

GeneTests
GCH1
GeneReviews
GCH1
Genetic Association Database (GAD)
GCH1
Human Genome Epidemiology (HuGE) Navigator
GCH1
genes like me logo Genes that share disorders with GCH1: view

Publications for GCH1 Gene

  1. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. (PMID: 7874165) Ichinose H. … Nagatsu T. (Nat. Genet. 1994) 2 3 4 23
  2. Human GTP cyclohydrolase I: only one out of three cDNA isoforms gives rise to the active enzyme. (PMID: 8068008) Guetlich M. … Bacher A. (Biochem. J. 1994) 3 4 23
  3. Multiple mRNA forms of human GTP cyclohydrolase I. (PMID: 1520321) Togari A. … Nagatsu T. (Biochem. Biophys. Res. Commun. 1992) 3 4 23
  4. Cloning, sequencing and functional studies of the gene encoding human GTP cyclohydrolase I. (PMID: 8666288) Witter K. … Guetlich M. (Gene 1996) 3 4 23
  5. Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP. (PMID: 7678411) Werner-Felmayer G. … Wachter H. (J. Biol. Chem. 1993) 3 4 23

Products for GCH1 Gene

Sources for GCH1 Gene

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