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GCH1 Gene

protein-coding   GIFtS: 70
GCID: GC14M055308

GTP Cyclohydrolase 1

(Previous name: dystonia 14)
(Previous symbols: GCH, DYT5, DYT14)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
GTP Cyclohydrolase 11 2     EC 3.5.4.163 8
DYT51 2 3 5     HPABH4B2 5
GCH1 2 3     Dopa-Responsive Dystonia1
DYT141 2     DYT5a2
Dystonia 141 2     GTP-CH-12
GTP-CH-I2 3     GTPCH12
GTP Cyclohydrolase I2 3     Guanosine 5'-Triphosphate Cyclohydrolase I2

External Ids:    HGNC: 41931   Entrez Gene: 26432   Ensembl: ENSG000001319797   OMIM: 6002255   UniProtKB: P307933   

Export aliases for GCH1 gene to outside databases

Previous GC identifers: GC14M052632 GC14M049104 GC14M053298 GC14M054378 GC14M035471


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 dystonia 5, dopa-responsive type, and dystonia, dopa-responsive, with or without hyperphenylalaninemia. GO annotations related to this gene include GTP binding and calcium ion binding.

UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793
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

Gene Wiki entry for GCH1 (GTP cyclohydrolase I) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000014.9  NT_026437.13  NC_018925.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the GCH1 gene promoter:
         AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGCH1 promoter sequence
   Search Chromatin IP Primers for GCH1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GCH1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q22.1-q22.2   Ensembl cytogenetic band:  14q22.2   HGNC cytogenetic band: 14q22.1-q22.2

GCH1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GCH1 gene location

GeneLoc information about chromosome 14         GeneLoc Exon Structure

GeneLoc location for GC14M055308:  view genomic region     (about GC identifiers)

Start:
55,308,723 bp from pter      End:
55,369,570 bp from pter
Size:
60,848 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793 (See protein sequence)
Recommended Name: GTP cyclohydrolase 1  
Size: 250 amino acids; 27903 Da
Subunit: 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
1 PDB 3D structure from and Proteopedia for GCH1:
1FB1 (3D)    
Secondary accessions: Q6FHY7 Q9Y4I8
Alternative splicing: 4 isoforms:  P30793-1   P30793-2   P30793-3   P30793-4   

Explore the universe of human proteins at neXtProt for GCH1: NX_P30793

Explore proteomics data for GCH1 at MOPED

Post-translational modifications: 

  • Phosphorylated by casein kinase II at Ser-81 in HAECs during oscillatory shear stress; phosphorylation at Ser-81
    results in increased enzyme activity1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for GCH1 (P30793) (see all 8)
     QVQERLT  FDEDHDE  SKLARIV  GLSKLAR 


    See GCH1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_000152.1  NP_001019195.1  NP_001019241.1  NP_001019242.1  

    ENSEMBL proteins: 
     ENSP00000444011   ENSP00000419045   ENSP00000445246   ENSP00000378890  
    Reactome Protein details: P30793

    GCH1 Human Recombinant Protein Products:

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    Novus Biologicals GCH1 Proteins
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    Cloud-Clone Corp. Proteins for GCH1

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    Cloud-Clone Corp. CLIAs for GCH1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR001474 GTP_CycHdrlase_I
     IPR020602 GTP_CycHdrlase_I_dom
     IPR018234 GTP_CycHdrlase_I_CS

    Graphical View of Domain Structure for InterPro Entry P30793

    ProtoNet protein and cluster: P30793

    1 Blocks protein domain: IPB001474 GTP cyclohydrolase I

    UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793
    Similarity: Belongs to the GTP cyclohydrolase I family


    GCH1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: GCH1_HUMAN, P30793
    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
    Catalytic activity: GTP + H(2)O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine
    triphosphate
    Enzyme regulation: GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity.
    Zinc is required for catalytic activity. Inhibited by Mg(2+)
    Biophysicochemical properties: Kinetic parameters: KM=116 uM for GTP; pH dependence: Optimum pH is 7.7 in
    phosphate buffer; Temperature dependence: Relatively stable at high temperatures. Retains 50% of its activity
    after incubation at 70 degrees Celsius for 15 minutes;
    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)

         Genatlas biochemistry entry for GCH1:
    GTP cyclohydrolase I,catalyzing the first step of tetrahydrobiopterin (BH4) synthesis

         Enzyme Number (IUBMB): EC 3.5.4.161 2

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003934NOT GTP cyclohydrolase I activity IDA11284739
    GO:0005509calcium ion binding IEA--
    GO:0005515protein binding IPI16696853
    GO:0005525GTP binding IDA14717702
    GO:0008270zinc ion binding IDA11087823
         
    GCH1 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for GCH1:
     Increased cell number in G2M,  

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for GCH1
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for GCH1

    miRNA
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    miRTarBase miRNAs that target GCH1:
    hsa-mir-18a-5p (MIRT050671), hsa-mir-26b-5p (MIRT029667), hsa-mir-215-5p (MIRT024891), hsa-mir-335-5p (MIRT018241), hsa-mir-192-5p (MIRT026625), hsa-mir-124-3p (MIRT022842), hsa-mir-1 (MIRT002772)

    Block miRNA regulation of human, mouse, rat GCH1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate GCH1 (see all 23):
    hsa-miR-875-3p hsa-miR-3938 hsa-miR-605 hsa-miR-449a hsa-miR-1304 hsa-miR-124 hsa-miR-9 hsa-miR-133a
    SwitchGear 3'UTR luciferase reporter plasmidGCH1 3' UTR sequence
    Inhib. RNA
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GCH1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    GCH1_HUMAN, P30793: Cytoplasm. Nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol5
    nucleus5
    extracellular1
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--
    GO:0031410cytoplasmic vesicle IDA3318829

    GCH1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for GCH1 About                                                                                                See pathways by source

    SuperPathContained pathways About
    1Metabolism of nitric oxide
    Metabolism of nitric oxide
    tetrahydrobiopterin de novo biosynthesis0.00
    eNOS activation and regulation0.00
    Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation0.00
    2Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    3Folate biosynthesis
    Folate biosynthesis

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 BioSystems Pathway for GCH1
        tetrahydrobiopterin de novo biosynthesis

    1 Reactome Pathway for GCH1
        Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation


    2 Kegg Pathways  (Kegg details for GCH1):
        Folate biosynthesis
    Metabolic pathways

    UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793
    Pathway: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate biosynthesis; 7,8-dihydroneopterin triphosphate
    from GTP: step 1/1


    GCH1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GCH1: 

              Hypertension in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Neurotoxicity in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for GCH1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for GCH1 (P307931, 2, 3 ENSP000003788904) via UniProtKB, MINT, STRING, and/or I2D (see all 196)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CDC37Q165432, 3MINT-8250889 I2D: score=2 
    SH3GL2Q999622, 3MINT-8270462 I2D: score=2 
    AHSA1O954331, 3, ENSP000002164794EBI-958183,EBI-448610 I2D: score=4 STRING: ENSP00000216479
    RLFQ131293, ENSP000003618574I2D: score=3 STRING: ENSP00000361857
    RAB26Q9ULW53, ENSP000002101874I2D: score=2 STRING: ENSP00000210187
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    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006184GTP catabolic process IDA2463916
    GO:0006461protein complex assembly ----
    GO:0006729tetrahydrobiopterin biosynthetic process IMP17101830
    GO:0006809nitric oxide biosynthetic process NAS9445252
    GO:0008152metabolic process IDA3753653

    GCH1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for GCH1
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    Browse Tocris compounds for GCH1

    8 HMDB Compounds for GCH1    About this table
    CompoundSynonyms CAS #PubMed Ids
    Tetrahydrobiopterin(1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol (see all 11)17528-72-29165069
    2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine ----
    2,5-Diaminopyrimidine nucleoside triphosphate ----
    Dihydroneopterin triphosphate2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl) dihydropteridine triphosphate (see all 5)20574-65-6--
    Formamidopyrimidine nucleoside triphosphate ----
    Formic acidAdd-F (see all 21)64-18-6--
    Guanosine triphosphate5'-GTP (see all 10)86-01-1--
    WaterDihydrogen oxide (see all 2)7732-18-5--

    1 DrugBank Compound for GCH1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Guanine-- 73-40-5targetinhibitor11752352

    Selected Novoseek inferred chemical compound relationships for GCH1 gene (see all 46)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tetrahydrobiopterin 96.8 140 19926872 (2), 12607127 (2), 14717702 (2), 11799107 (2) (see all 95)
    gtp 94.1 575 1356983 (6), 11274478 (6), 10049741 (6), 8068008 (5) (see all 99)
    sepiapterin 92.3 20 2154472 (3), 19234759 (2), 12003346 (1), 15197144 (1) (see all 16)
    6-pyruvoyltetrahydropterin 90.9 18 2154472 (3), 9222755 (2), 12003346 (1), 15197144 (1) (see all 14)
    2,4-diamino-6-hydroxypyrimidine 87.7 7 9843157 (1), 7531790 (1), 15292175 (1), 9252248 (1) (see all 5)
    dihydroneopterin triphosphate 86.4 4 10358012 (1), 9165069 (1), 9774432 (1), 11425318 (1)
    dihydropteridine 83.8 6 12003346 (1), 16275037 (1), 19234759 (1), 8830181 (1) (see all 6)
    neopterin 82.1 21 9566389 (4), 9128393 (1), 10496263 (1), 9577670 (1) (see all 13)
    4a-hydroxytetrahydrobiopterin 78.6 1 7769265 (1)
    dihydrobiopterin 78 3 19286667 (1)



    GCH1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for GCH1 gene (4 alternative transcripts): 
    NM_000161.2  NM_001024024.1  NM_001024070.1  NM_001024071.1  

    Unigene Cluster for GCH1:

    GTP cyclohydrolase 1
    Hs.86724  [show with all ESTs]
    Unigene Representative Sequence: NM_000161
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000543643 ENST00000491895(uc001xbi.1 uc001xbj.1) ENST00000254299
    ENST00000536224 ENST00000395521 ENST00000395514(uc001xbh.1 uc001xbk.1 uc010aol.1 uc001xbl.1)

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Selected qRT-PCR Assays for microRNAs that regulate GCH1 (see all 23):
    hsa-miR-875-3p hsa-miR-3938 hsa-miR-605 hsa-miR-449a hsa-miR-1304 hsa-miR-124 hsa-miR-9 hsa-miR-133a
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    Additional mRNA sequence: 

    AF321276.1 AY137463.1 AY137464.1 AY137465.1 BC025415.2 CR536551.1 S44049.1 S44053.1 
    U19523.1 U66095.1 U66097.1 Z16418.1 Z29433.2 Z29434.2 

    7 DOTS entries:

    DT.453978  DT.100793225  DT.100831010  DT.91740520  DT.95169985  DT.120779453  DT.75160262 

    Selected AceView cDNA sequences (see all 141):

    CA307458 BM828037 AY137463 AY137465 CD639815 BQ217847 AL699561 CR536551 
    AF321276 AU139135 BM827139 CR589979 CB159554 CK820966 U66097 AA679434 
    BU949053 BI222874 T27726 AI383255 BU949048 BM856936 BM841300 AI246757 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for GCH1    About this scheme

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


    ECgene alternative splicing isoforms for GCH1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    GCH1 expression in normal human tissues (normalized intensities)      GCH1 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATCTTGAGTC
    GCH1 Expression
    About this image


    GCH1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Bone (Muscoskeletal System)    fully expand to see all 3 entries
             Membranous Facial Bones
             Bone marrow-derived mesenchymal stem cells
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Cerebral Cortex
     
     Mesenchymal Stem Cells
             Bone marrow-derived mesenchymal stem cells
     
     Eye (Sensory Organs)
             Lens
     
     Neural Tube (Nervous System)
             Telencephalon
    GCH1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GCH1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.86724

    UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793
    Tissue specificity: In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but
    not all melanocytes (at protein level)

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GCH1: 
              Hypertension in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Neurotoxicity in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for GCH1 gene from Selected species (see all 22)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Gch11 , 5 GTP cyclohydrolase 11, 5 88.19(n)1
    89.17(a)1
      14 (24.60 cM)5
    145281  NM_008102.31  NP_032128.11 
     471538955 
    chicken
    (Gallus gallus)
    Aves GCH11 GTP cyclohydrolase 1 81.97(n)
    84.55(a)
      396146  NM_205223.1  NP_990554.1 
    lizard
    (Anolis carolinensis)
    Reptilia GCH16
    GTP cyclohydrolase 1
    75(a)
    1 ↔ 1
    2(142845521-142856658)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia Str.60982 Transcribed sequence with moderate similarity to protein more 80.95(n)    CF239391.1 
    zebrafish
    (Danio rerio)
    Actinopterygii gch2 GTP cyclohydrolase 1 76.98(n)   64263  AJ311846.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Pu1 , 3 ommochrome biosynthesis GTP
    cyclohydrolase I3
    Punch1
    75(a)3
    69.03(n)1
    76.5(a)1
      374151  NM_166431.41  NP_726038.11 
    worm
    (Caenorhabditis elegans)
    Secernentea F32G8.63
    cat-41
    GTP cyclohydrolase I3
    cat-41
    71(a)3
    65.4(n)1
    71.74(a)1
      V(10567504-10568847)3
    1794721  NM_073309.51  NP_505710.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes FOL21 FOL2 56.62(n)
    59.33(a)
      853183   NP_011783.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for GCH1 (see all 1490)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 14 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs412984421,2,,4
    CGTP cyclohydrolase 1 deficiency (GCH1D)4 pathogenic136294064(-) CAGCAA/GAACTG 6 K R mis1 int12Minor allele frequency- G:0.00NA EU 1325
    rs412984321,2,,4
    CDystonia 5 (DYT5)4 --36352665(-) GTTCCC/TCGAGC 8 P L mis11Minor allele frequency- T:0.00NA 2
    VAR_0169074
    Dystonia 5 (DYT5)4--see VAR_0169072 R S mis40--------
    VAR_0026434
    GTP cyclohydrolase 1 deficiency (GCH1D)4--see VAR_0026432 R H mis40--------
    VAR_0026364
    Dystonia 5 (DYT5)4--see VAR_0026362 R W mis40--------
    VAR_0169044
    Dystonia 5 (DYT5)4--see VAR_0169042 M V mis40--------
    VAR_0026424
    Dystonia 5 (DYT5)4--see VAR_0026422 R S mis40--------
    VAR_0169064
    Dystonia 5 (DYT5)4--see VAR_0169062 R W mis40--------
    VAR_0168904
    Dystonia 5 (DYT5)4--see VAR_0168902 G A mis40--------
    VAR_0026384
    Dystonia 5 (DYT5)4--see VAR_0026382 D V mis40--------

    HapMap Linkage Disequilibrium report for GCH1 (55308723 - 55369570 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for GCH1:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2675781CNV Deletion23128226
    esv2659466CNV Deletion23128226
    esv2661782CNV Deletion23128226
    nsv819735CNV Loss19587683

    Human Gene Mutation Database (HGMD): GCH1
    Locus Specific Mutation Databases (LSDB): GCH1

    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing GCH1
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600225   
    OMIM disorders: 128230  233910  
    UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793
  • GTP cyclohydrolase 1 deficiency (GCH1D) [MIM:233910]: A cause of malignant hyperphenylalaninemia due to
    tetrahydrobiopterin deficiency. It is also responsible for 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 type 5 (dystonia-parkinsonism with diurnal fluctuation). In this
    intermediate phenotype, there is marked motor delay, but no mental retardation and only minimal, if any,
    hyperphenylalaninemia. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Dystonia 5 (DYT5) [MIM:128230]: A DOPA-responsive dystonia. Dystonia is defined by the presence of
    sustained involuntary muscle contractions, often leading to abnormal postures. DYT5 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. There is a
    favorable response to L-DOPA without side effects. Note=The disease is caused by mutations affecting the gene
    represented in this entry

  • Selected diseases for GCH1 (see all 66):    About MalaCards
    dystonia 5, dopa-responsive type    dystonia, dopa-responsive, with or without hyperphenylalaninemia    gtp cyclohydrolase 1-related disorders    gtp cyclohydrolase i deficiency
    oromandibular dystonia    gtp cyclohydrolase 1-deficient dopa-responsive dystonia    tyrosine hydroxylase deficiency    torsion dystonia
    hyperphenylalaninemia    myoclonus-dystonia    cervical dystonia    tetrahydrobiopterin deficiency
    basal ganglia disease    biotin-responsive basal ganglia disease    somatoform disorder    dystonia musculorum deformans
    blepharospasm    low renin hypertension    complex regional pain syndrome    back pain

    5 diseases from the University of Copenhagen DISEASES database for GCH1:
    Parkinson's disease     Movement disease     Phenylketonuria     Choriocarcinoma
    Cerebral palsy

    GCH1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for GCH1 gene (see all 22)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    gtp cyclohydrolase i deficiency 96.1 25 12891655 (3), 7730309 (2), 10321973 (2), 10582612 (1) (see all 14)
    dystonia 5 89 7 10762165 (1), 19735094 (1), 11464453 (1), 16289769 (1)
    hyperphenylalaninemia 85.1 11 17432176 (1), 18241680 (1), 9921872 (1), 16275037 (1) (see all 9)
    dystonia hereditary 73.9 1 10208576 (1)
    torsion dystonia 73.5 7 9328244 (2), 9778264 (1), 12194383 (1), 15679701 (1) (see all 5)
    dystonia primary 70.3 1 17061184 (1)
    secondary dystonia 65.4 1 19491146 (1)
    parkinsonism 62.2 2 18511327 (1), 10495030 (1)
    movement disorders 57.3 3 19566901 (1), 18044725 (1), 15786464 (1)
    parkinson disease 54.3 16 16708545 (2), 16267845 (2), 9592104 (2), 9182249 (1) (see all 12)

    GeneTests: GCH1
    GeneReviews: GCH1
    Genetic Association Database (GAD): GCH1
    Human Genome Epidemiology (HuGE) Navigator: GCH1 (30 documents)

    Export disorders for GCH1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for GCH1 gene, integrated from 10 sources (see all 375):
    (articles sorted by number of sources associating them with GCH1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. (PubMed id 7874165)1, 2, 3, 9 Ichinose H.... Nagatsu T. (Nat. Genet. 1994)
    2. Isolation of a full-length cDNA clone for human GTP cyclohydrolase I type 1 from pheochromocytoma. (PubMed id 8695054)1, 2, 3 Nomura T.... Nagatsu T. (J. Neural Transm. 1995)
    3. GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide production and endothelial function. (PubMed id 18598896)1, 4, 9 Antoniades C....Channon K.M. (J. Am. Coll. Cardiol. 2008)
    4. GCH1 in early-onset Parkinson's disease. (PubMed id 19735094)1, 4, 9 Cobb S.A....Farrer M.J. (Mov. Disord. 2009)
    5. Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk. (PubMed id 17717598)1, 4, 9 Zhang L....O'Connor D.T. (J. Clin. Invest. 2007)
    6. A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions. (PubMed id 16696853)1, 2, 9 Swick L. and Kapatos G. (J. Neurochem. 2006)
    7. Cross-sectional assessment of the consequences of a GTP cyclohydrolase 1 haplotype for specialized tertiary outpatient pain care. (PubMed id 19851158)1, 4, 9 Doehring A....LAPtsch J. (Clin J Pain 2009)
    8. Frequency of GCH1 deletions in Dopa-responsive dystonia. (PubMed id 17898029)1, 4, 9 Zirn B....MA1ller U. (J. Neurol. Neurosurg. Psychiatr. 2008)
    9. Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms. (PubMed id 17363416)1, 4, 9 LAPtsch J....Tegeder I. (Clin. Chem. 2007)
    10. A GTP cyclohydrolase 1 genetic variant delays cancer pain. (PubMed id 19959292)1, 4, 9 LAPtsch J....Dale O. (Pain 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2643 HGNC: 4193 AceView: GCH1 Ensembl:ENSG00000131979 euGenes: HUgn2643
    ECgene: GCH1 Kegg: 2643 H-InvDB: GCH1

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for GCH1 Pharmacogenomics, SNPs, Pathways
    BIOMDBhttp://www.bh4.org/biodef1.html
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=GCH1[genesymbol]

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for GCH1 gene:
    Search GeneIP for patents involving GCH1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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