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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

GCH1 Gene

protein-coding   GIFtS: 69
GCID: GC14M055308

GTP cyclohydrolase 1

(Previous name: dystonia 14 )
(Previous symbols: GCH, DYT5, DYT14)
 Explore 62 diseases affiliated with
GCH1 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for GCH1    

Aliases
for GCH1 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
GTP Cyclohydrolase 11 2     GTP-CH-I2 3
DYT51 2 3 5     GTP Cyclohydrolase I2 3
GCH1 2 3     EC 3.5.4.163 8
DYT141 2     HPABH4B2 5
DYT5a1 2     GTP-CH-12
GTPCH11 2     Guanosine 5'-Triphosphate Cyclohydrolase I2
Dystonia 141 2     

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


Summaries
for GCH1 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for GCH1:
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)

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)


Genomic Views
for GCH1 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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000014.8  NC_018925.1  NT_026437.12  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the GCH1 gene promoter:
         AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: GCH1 promoter sequence
   Search SABiosciences Chromatin IP Primers for GCH1

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for GCH1 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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
Subcellular location: Cytoplasm. Nucleus
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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P30793

    • 4/8 DME Specific Peptides for GCH1 (P30793) (see all 8)
     QVQERLT  FDEDHDE  SKLARIV  GLSKLAR 

    GCH1 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    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
    Human Recombinant Protein Products: 
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    Novus Biologicals GCH1 Proteins
    Novus Biologicals GCH1 Lysates
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    Browse ProSpec Recombinant Proteins
    Uscn Proteins for GCH1

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005625soluble fraction ----
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--


    GCH1 for ontologies           About GeneDecksing



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    Uscn ELISAs and CLIAs for GCH1

    Protein Domains /
    Families
    for GCH1 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    GCH1 for domains           About GeneDecksing

    3 InterPro domains/families:
     IPR001474 GTP_CycHdrlase_I
     IPR020602 GTP_CycHdrlase_I/CN_OxRdtase
     IPR018234 GTP_CycHdrlase_I_CS

    Graphical View of Domain Structure for InterPro Entry P30793

    ProtoNet protein and cluster: P30793

    1 Blocks protein family: IPB001474 GTP cyclohydrolase I

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


    Function
    for GCH1 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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
    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

    miRNA
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    hsa-mir-1 (MIRT002772)

    OriGene 3'-UTR Clone (see all 4): GCH1
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat GCH1
    8/23 QIAGEN miScript miRNA 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 plasmid: GCH1 3' UTR sequence
    Inhib. RNA
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    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat GCH1

    Gene Editing
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    Clone
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    Cell Line
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    Search LifeMap BioReagents cell lines for GCH1

    In Situ Assay
    Products:       
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    Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (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 IPI--
    GO:0005525GTP binding IDA14717702
    GO:0008270zinc ion binding IDA11087823


    GCH1 for ontologies           About GeneDecksing


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


    Pathways & Interactions
    for GCH1 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways  About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Metabolism of nitric oxide
    		eNOS activation and regulation1.00
    		tetrahydrobiopterin biosynthesis II0.18
    		Metabolism of nitric oxide1.00
    		tetrahydrobiopterin biosynthesis I0.18
    		Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation0.59
    2Metabolism
    		Metabolism1.00
    		Metabolic pathways0.38
    3Folate biosynthesis
    		Folate biosynthesis1.00

    Pathway sources
    See GeneCards unified pathways
    Show all pathways


    2 BioSystems Pathways for GCH1 
        tetrahydrobiopterin biosynthesis II
    tetrahydrobiopterin biosynthesis I

    4        Reactome Pathways for GCH1
        eNOS activation and regulation
    Metabolism of nitric oxide
    Metabolism
    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

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for GCH1

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

    5/187 Interacting proteins for GCH1 (P307931, 2, 3 ENSP000003788904) via UniProtKB, MINT, STRING, and/or I2D (see all 187)

    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
    NTMT1Q9BV863, ENSP000003615584I2D: score=2 STRING: ENSP00000361558
    About this table

    Gene Ontology (GO): 5/25 biological process terms (GO ID links to tree view) (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:0006917induction of apoptosis IEA--


    GCH1 for ontologies           About GeneDecksing



    Drugs & Compounds
    for GCH1 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    GCH1 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Enzo Life Sciences drugs & compounds for GCH1

    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

    10/46 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about GCH1 

    Transcripts
    for GCH1 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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)


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    Inhib. RNA
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    Clone
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    Primer
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    Additional cDNA 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 

    24/141 AceView cDNA sequences (see all 141):

    CR536551 BM828037 AU139135 CK820966 CR589979 AF321276 AL699561 BQ217847 
    U66097 AY137465 CB159554 CA307458 BM827139 AY137463 CD639815 T28949 
    BU949048 U66095 AI951824 S43856 AA343920 CB178782 BI964927 BC025415 

    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

    Expression
    for GCH1 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    GCH1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: ATCTTGAGTC

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image
    See GCH1 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for GCH1

    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)

        SABiosciences Expression via Pathway-Focused 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
    for GCH1 gene

    (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)
    About This Section
    This gene was present in the last universal common ancestor (LUCA).

    Orthologs for GCH1 gene from 11/38 species (see all 38)    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
    		 --
    		 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
    68.64(n)1
    75.81(a)1    		   374151  NM_166431.31  NP_726038.11 
    worm
    (Caenorhabditis elegans)    		 Secernentea F32G8.63
    cat-41    		 GTP cyclohydrolase I3
    Protein CAT-41    		 71(a)3
    65.4(n)1
    71.74(a)1    		   V(10567504-10568847)3
    1794721  NM_073309.41  NP_505710.11 
    baker's yeast
    (Saccharomyces cerevisiae)    		 Saccharomycetes FOL21 Fol2p 56.62(n)
    59.33(a)    		   853183   NP_011783.1 
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons AT3G072701 GTP cyclohydrolase I 49.17(n)
    41.99(a)    		   819915  NM_202517.1  NP_974246.1 
    rice
    (Oryza sativa)    		 Liliopsida Os04g06627001 hypothetical protein 49.33(n)
    41.14(a)    		   4337297  NM_001060693.1  NP_001054158.1 


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

    Paralogs
    for GCH1 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    		  --

    Genomic Variants
    for GCH1 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1134 NCBI SNPs in GCH1 are shown (see all 1134)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 14 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs1048944421,2
    		Cpathogenic35473356(-) ATTAGC/GAGCTG 6 S R mis1 int10--------
    rs412984421,2
    		C,pathogenic35473432(-) CAGCAA/GAACTG 6 K R int1 mis12Minor allele frequency- G:0.00NA EU 1325
    rs1048944431,2
    		Cpathogenic35473470(-) CACATA/GTGTAT 6 I M int1 mis10--------
    rs1048944381,2
    		Cpathogenic35475125(-) TGCTGA/GAGTCG 8 E G mis10--------
    rs1048944361,2
    		Cpathogenic35475141(-) CGGAAG/TCCTTG 8 A S mis10--------
    rs1048944451,2
    		Cpathogenic35475176(-) GGAGCA/GCCTTA 8 H R mis10--------
    rs1048944401,2
    		Cpathogenic35494681(-) GCATCA/CCTTGG 8 H P mis10--------
    rs1048944411,2
    		Cpathogenic35494708(-) GGACAA/TAGACA 8 K I mis10--------
    rs1048944371,2
    		Cpathogenic35494711(-) GAAGGA/TCATAG 8 D V mis10--------
    rs1048944351,2
    		Cpathogenic35531626(-) CAAGGA/GCTACC 8 D G mis10--------

    HapMap Linkage Disequilibrium report for GCH1 (55308723 - 55369570 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for GCH1
         1 CNV: 58682
    Human Gene Mutation Database (HGMD): GCH1

    Locus Specific Mutation Databases (LSDB): GCH1

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    Disorders / Diseases
    for GCH1 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    GCH1 for disorders           About GeneDecksing

    OMIM gene information: 600225   
    OMIM disorders: 233910  
    UniProtKB/Swiss-Prot: GCH1_HUMAN, P30793
  • Defects in GCH1 are the cause of GTP cyclohydrolase 1 deficiency (GCH1D) [MIM:233910]; also known as atypical
    • severe phenylketonuria due to GTP cyclohydrolase I deficiency;. GCH1D is one of the causes 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
  • Defects in GCH1 are the cause of dystonia type 5 (DYT5) [MIM:128230]; also known as progressive dystonia with
    • diurnal fluctuation, autosomal dominant Segawa syndrome or dystonia-parkinsonism with diurnal fluctuation. DYT5 is 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 excercise. There is a favorable response to L-DOPA without side effects

    20/62 diseases for GCH1 (see all 62):    About MalaCards
    dopa-responsive dystonia    gtp cyclohydrolase 1-deficient dopa-responsive dystonia    dystonia, dopa-responsive, with or without hyperphenylalainemia    gtp cyclohydrolase i deficiency
    hyperphenylalaninemia    biotin-responsive basal ganglia disease    dystonia musculorum deformans    tyrosine hydroxylase deficiency
    torsion dystonia    myoclonus-dystonia    hermansky-pudlak syndrome    complex regional pain syndrome
    degenerative disc disease    basal ganglia disease    back pain    segawa syndrome
    tetrahydrobiopterin deficiency    somatoform disorder    spastic paraplegia    essential tremor

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

    10/22 Novoseek 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
    GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia

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

    Export disorders for GCH1 gene to outside databases

    Publications
    for GCH1 gene

    (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)
    About This Section

    PubMed articles for GCH1 gene, integrated from 9 sources (see all 362):
    (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. (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. (1995)
    3. A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions. (PubMed id 16696853)1, 2, 9 Swick L. and Kapatos G. (2006)
    4. GTP cyclohydrolase I utilizes metal-free GTP as its substrate. (PubMed id 14717702)1, 2, 9 Suzuki T.... Ichinose H. (2004)
    5. Role of human GTP cyclohydrolase I and its regulatory protein in tetrahydrobiopterin metabolism. (PubMed id 12607127)1, 2, 9 Gesierich A.... Tiefenbacher C.P. (2003)
    6. A novel missense mutant inactivates GTP cyclohydrolase I in dopa- responsive dystonia. (PubMed id 10076897)1, 2, 9 Hirano M.... Ueno S. (1999)
    7. Dystonia with motor delay in compound heterozygotes for GTP- cyclohydrolase I gene mutations. (PubMed id 9667588)1, 2, 9 Furukawa Y.... Trugman J.M. (1998)
    8. Dopa-responsive dystonia: a clinical and molecular genetic study. (PubMed id 9778264)1, 2, 9 Bandmann O.... Wood N.W. (1998)
    9. Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. (PubMed id 7730309)1, 2, 9 Ichinose H.... Nagatsu T. (1995)
    10. Human GTP cyclohydrolase I: only one out of three cDNA isoforms gives rise to the active enzyme. (PubMed id 8068008)1, 2, 9 Guetlich M.... Bacher A. (1994)

    External Searches for GCH1 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
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    Genome Databases showing GCH1 gene

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

    Other Databases showing GCH1 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing GCH1 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for GCH1 Pharmacogenomics, SNPs, Pathways
    BIOMDBhttp://www.bh4.org/biodef1.html
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GCH1

    Intellectual Property
    for GCH1 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		Patent Information for GCH1 gene:
    Search GeneIP for patents involving GCH1

    GeneCards and IP:
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