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Aliases for GCH1 Gene

Aliases for GCH1 Gene

  • GTP Cyclohydrolase 1 2 3 5
  • GTP Cyclohydrolase I 3 4
  • Dystonia 14 2 3
  • EC 4 63
  • GTP-CH-I 3 4
  • DYT5 3 4
  • GCH 3 4
  • Guanosine 5-Triphosphate Cyclohydrolase I 3
  • Dopa-Responsive Dystonia 2
  • GTP-CH-1 3
  • HPABH4B 3
  • GTPCH1 3
  • DYT5a 3
  • DYT14 3

External Ids for GCH1 Gene

Previous HGNC Symbols for GCH1 Gene

  • GCH
  • DYT5
  • DYT14

Previous GeneCards Identifiers for GCH1 Gene

  • GC14M052632
  • GC14M049104
  • GC14M053298
  • GC14M054378
  • GC14M055308
  • GC14M035471

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 Hyperphenylalaninemia, Bh4-Deficient, B and Dystonia, Dopa-Responsive, With Or Without Hyperphenylalaninemia. Among its related pathways are eNOS activation and regulation and Folate biosynthesis. 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

Regulatory Elements for GCH1 Gene

Enhancers for GCH1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around GCH1 on UCSC Golden Path with GeneCards custom track

Promoters for GCH1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around GCH1 on UCSC Golden Path with GeneCards custom track

Genomic Location for GCH1 Gene

54,842,005 bp from pter
54,902,885 bp from pter
60,881 bases
Minus strand

Genomic View for GCH1 Gene

Genes around GCH1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GCH1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GCH1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GCH1 Gene

Proteins for GCH1 Gene

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

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

    Protein attributes for GCH1 Gene

    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


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

Domains & Families for GCH1 Gene

Protein Domains for GCH1 Gene

Suggested Antigen Peptide Sequences for GCH1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the GTP cyclohydrolase I family.
  • Belongs to the GTP cyclohydrolase I family.
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

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

Human Phenotype Ontology for GCH1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

No data available for Gene Ontology (GO) - Molecular Function , Animal Models , Transcription Factor Targets and HOMER Transcription for GCH1 Gene

Localization for GCH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GCH1 Gene

Cytoplasm. Nucleus.

Subcellular locations from

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

Gene Ontology (GO) - Cellular Components for GCH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0031965 nuclear membrane IDA --
genes like me logo Genes that share ontologies with GCH1: view

Pathways & Interactions 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:0006729 tetrahydrobiopterin biosynthetic process IMP 17101830
GO:0006809 nitric oxide biosynthetic process NAS 9445252
GO:0014916 regulation of lung blood pressure IEA --
GO:0035998 7,8-dihydroneopterin 3-triphosphate biosynthetic process IEA --
GO:0044281 small molecule metabolic process TAS --
genes like me logo Genes that share ontologies with GCH1: view

No data available for SIGNOR curated interactions for GCH1 Gene

Drugs & Compounds for GCH1 Gene

(25) Drugs for GCH1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tetrahydrobiopterin Approved, Investigational Pharma 0
Guanine Experimental Pharma Target, inhibitor 0
Formic acid Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0

(28) Additional Compounds for GCH1 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
dihydroneopterin triphosphate
  • 2-Amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl) dihydropteridine triphosphate
  • 6-(L-Erythro-1,2-Dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
  • 6-[(1S,2R)-1,2-Dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin
  • 7,8-Dihydroneopterin 3'-triphosphate
  • 7,8-Dihydroneopterin triphosphate
2,5-Diaminopyrimidine nucleoside triphosphate
Formamidopyrimidine nucleoside triphosphate
Isopropyl alcohol
  • 2-Propanol
  • 2-Propyl alcohol
  • Alcojel
  • Alkolave
  • Avantin
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: - - -

Relevant External Links for GCH1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

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 (x11.5).

Protein differential expression in normal tissues from HIPED for GCH1 Gene

This gene is overexpressed in Islet of Langerhans (25.3), Liver (25.2), and Adrenal (12.6).

Integrated Proteomics: protein expression in normal tissues and cell lines 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

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 expression patterns with GCH1: view

Protein tissue co-expression partners for GCH1 Gene

Primer Products

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
(Bos Taurus)
Mammalia GCH1 35
  • 89.96 (n)
  • 91.57 (a)
GCH1 36
  • 92 (a)
(Canis familiaris)
Mammalia GCH1 35
  • 93.71 (n)
  • 96.79 (a)
GCH1 36
  • 97 (a)
(Mus musculus)
Mammalia Gch1 35
  • 88.19 (n)
  • 89.17 (a)
Gch1 16
Gch1 36
  • 89 (a)
(Pan troglodytes)
Mammalia GCH1 35
  • 99.87 (n)
  • 100 (a)
GCH1 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Gch1 35
  • 90.28 (n)
  • 92.5 (a)
(Monodelphis domestica)
Mammalia GCH1 36
  • 58 (a)
(Ornithorhynchus anatinus)
Mammalia GCH1 36
  • 99 (a)
(Gallus gallus)
Aves GCH1 35
  • 81.97 (n)
  • 84.55 (a)
GCH1 36
  • 82 (a)
(Anolis carolinensis)
Reptilia GCH1 36
  • 75 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia gch1 35
  • 73.61 (n)
  • 80 (a)
Str.6098 35
(Danio rerio)
Actinopterygii gch 35
gch1 35
  • 78.17 (n)
  • 88 (a)
gch1 36
  • 71 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11719 35
fruit fly
(Drosophila melanogaster)
Insecta Pu 37
  • 75 (a)
Pu 35
  • 69.03 (n)
  • 76.5 (a)
Pu 36
  • 47 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006441 35
  • 65.79 (n)
  • 74.35 (a)
(Caenorhabditis elegans)
Secernentea F32G8.6 37
  • 71 (a)
cat-4 35
  • 65.4 (n)
  • 71.74 (a)
cat-4 36
  • 60 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGR335C 35
  • 59.1 (n)
  • 60.7 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A09735g 35
  • 59.28 (n)
  • 65.98 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FOL2 35
  • 56.62 (n)
  • 59.33 (a)
FOL2 36
  • 51 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.7353 35
bread mold
(Neurospora crassa)
Ascomycetes NCU07774 35
  • 61.61 (n)
  • 61.24 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPAC17A5.13 35
  • 56.47 (n)
  • 58.9 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 70 (a)
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

Gene Tree for GCH1 (if available)
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
VAR_002632 -
rs41298432 Dystonia, dopa-responsive (DRD) 54,902,596(-) GTTCC(C/T)CGAGC reference, missense
VAR_002634 Dystonia, dopa-responsive (DRD)
VAR_002635 Dystonia, dopa-responsive (DRD)
VAR_002636 Dystonia, dopa-responsive (DRD)

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

Variation tolerance for GCH1 Gene

Residual Variation Intolerance Score: 46% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.41; 8.95% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GCH1 Gene

Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GCH1 Gene

Disorders for GCH1 Gene

MalaCards: The human disease database

(26) MalaCards diseases for GCH1 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hyperphenylalaninemia, bh4-deficient, b
  • atypical severe phenylketonuria due to gtp cyclohydrolase i deficiency
dystonia, dopa-responsive, with or without hyperphenylalaninemia
  • autosomal dominant dopa-responsive dystonia
gtp cyclohydrolase i deficiency
  • hyperphenylalaninemia, bh4-deficient, b
gtp cyclohydrolase 1-deficient dopa-responsive dystonia
  • autosomal dominant dopa-responsive dystonia
gtp cyclohydrolase 1-related disorders
  • gch1-related disorders
- elite association - COSMIC cancer census association via MalaCards
Search GCH1 in MalaCards View complete list of genes associated with diseases


  • 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.
  • 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.

Relevant External Links for GCH1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with GCH1: view

No data available for Genatlas for GCH1 Gene

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 67
  2. Novel non-sense GCH1 mutation in a South African family diagnosed with dopa-responsive dystonia. (PMID: 19566901) Bardien S. … Carr J. (Eur. J. Neurol. 2010) 3 23
  3. GTP cyclohydrolase I phosphorylation and interaction with GTP cyclohydrolase feedback regulatory protein provide novel regulation of endothelial tetrahydrobiopterin and nitric oxide. (PMID: 19926872) Li L. … Chen W. (Circ. Res. 2010) 3 23
  4. A GTP cyclohydrolase 1 genetic variant delays cancer pain. (PMID: 19959292) LAPtsch J. … Dale O. (Pain 2010) 3 23
  5. GCH1 mutation and clinical study of Chinese patients with dopa-responsive dystonia. (PMID: 20108370) Liu X. … Shang H.F. (Mov. Disord. 2010) 3 23

Products for GCH1 Gene

Sources for GCH1 Gene