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    GCH1 GTP cyclohydrolase 1 [ Homo sapiens (human) ]

    Gene ID: 2643, updated on 17-Feb-2019

    Summary

    Official Symbol
    GCH1provided by HGNC
    Official Full Name
    GTP cyclohydrolase 1provided by HGNC
    Primary source
    HGNC:HGNC:4193
    See related
    Ensembl:ENSG00000131979 MIM:600225
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GCH; DYT5; DYT14; DYT5a; GTPCH1; HPABH4B; GTP-CH-1
    Summary
    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]
    Expression
    Broad expression in liver (RPKM 22.0), bone marrow (RPKM 9.4) and 19 other tissues See more
    Orthologs

    Genomic context

    See GCH1 in Genome Data Viewer
    Location:
    14q22.2
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 14 NC_000014.9 (54842005..54902824, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (55308723..55369603, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC112268133 Neighboring gene sterile alpha motif domain containing 4A Neighboring gene uncharacterized LOC729451 Neighboring gene RNA, U6atac small nuclear 9, pseudogene Neighboring gene microRNA 4308 Neighboring gene farnesyl diphosphate synthase pseudogene 3 Neighboring gene WD repeat and HMG-box DNA binding protein 1 Neighboring gene ribosomal protein SA pseudogene 13 Neighboring gene suppressor of cytokine signaling 4

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Dystonia 5, Dopa-responsive type Compare labs
    GTP cyclohydrolase I deficiency
    MedGen: C0268467 OMIM: 233910 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2016-05-12)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2016-05-12)

    ClinGen Genome Curation PagePubMed

    NHGRI GWAS Catalog

    Description
    Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
    NHGRI GWA Catalog
    Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.
    NHGRI GWA Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    NHGRI GWA Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of GTP cyclohydrolase 1 (GCH1) in primary human brain microvascular endothelial cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    GTP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    GTP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    GTP cyclohydrolase I activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    GTP cyclohydrolase I activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    GTP-dependent protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    GTPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    coenzyme binding IEA
    Inferred from Electronic Annotation
    more info
     
    mitogen-activated protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    translation initiation factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    zinc ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    zinc ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    7,8-dihydroneopterin 3'-triphosphate biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    cofactor metabolic process TAS
    Traceable Author Statement
    more info
     
    dopamine biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of blood pressure IEA
    Inferred from Electronic Annotation
    more info
     
    neuromuscular process controlling posture IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    nitric oxide biosynthetic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of heart rate IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of nitric-oxide synthase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of nitric-oxide synthase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein heterooligomerization IEA
    Inferred from Electronic Annotation
    more info
     
    protein homooligomerization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    pteridine-containing compound biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of blood pressure IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of lung blood pressure IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of removal of superoxide radicals IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to interferon-gamma IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to lipopolysaccharide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT response to lipopolysaccharide IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    response to pain ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    response to tumor necrosis factor IDA
    Inferred from Direct Assay
    more info
    PubMed 
    tetrahydrobiopterin biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    tetrahydrobiopterin biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    tetrahydrobiopterin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    tetrahydrofolate biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    vasodilation IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    neuron projection terminus TAS
    Traceable Author Statement
    more info
    PubMed 
    nuclear membrane IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    GTP cyclohydrolase 1
    Names
    GTP cyclohydrolase I
    GTP-CH-I
    dystonia 14
    guanosine 5'-triphosphate cyclohydrolase I
    NP_000152.1
    NP_001019195.1
    NP_001019241.1
    NP_001019242.1
    XP_016876707.1

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008647.1 RefSeqGene

      Range
      5001..65820
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000161.3NP_000152.1  GTP cyclohydrolase 1 isoform 1

      See identical proteins and their annotated locations for NP_000152.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as Type I, represents the longest transcript. Variants 1 and 2 encode the longest isoform (1), which is the active enzyme.
      Source sequence(s)
      AL133444, AL160471
      Consensus CDS
      CCDS9720.1
      UniProtKB/Swiss-Prot
      P30793
      UniProtKB/TrEMBL
      A0A024R642
      Related
      ENSP00000477796.1, ENST00000622544.4
      Conserved Domains (1) summary
      cd00642
      Location:66250
      GTP_cyclohydro1; GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In ...
    2. NM_001024024.1NP_001019195.1  GTP cyclohydrolase 1 isoform 1

      See identical proteins and their annotated locations for NP_001019195.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also known as Type V, differs in the 3' UTR, compared to variant 1. Variants 1 and 2 both encode the functional enzyme, isoform 1.
      Source sequence(s)
      AL160471, AY137463, BM971258, U66095
      Consensus CDS
      CCDS9720.1
      UniProtKB/Swiss-Prot
      P30793
      UniProtKB/TrEMBL
      A0A024R642, Q8IZH9
      Related
      ENSP00000378890.1, ENST00000395514.5
      Conserved Domains (1) summary
      cd00642
      Location:66250
      GTP_cyclohydro1; GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In ...
    3. NM_001024070.1NP_001019241.1  GTP cyclohydrolase 1 isoform 2

      See identical proteins and their annotated locations for NP_001019241.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as Type IV, uses alternate, in-frame splice sites in the 3' coding region and 3' UTR, compared to variant 1. The resulting non-functional protein (isoform 2) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL160471, BM971258, U66095
      Consensus CDS
      CCDS41954.1
      UniProtKB/Swiss-Prot
      P30793
      Related
      ENSP00000444011.2, ENST00000543643.6
      Conserved Domains (1) summary
      cl00263
      Location:66209
      TFold; Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl ...
    4. NM_001024071.1NP_001019242.1  GTP cyclohydrolase 1 isoform 3

      See identical proteins and their annotated locations for NP_001019242.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), also known as Type II, lacks an alternate in-frame exon in the 3' coding region and uses a downstream stop codon, compared to variant 1. The resulting non-functional protein (isoform 3) is shorter and has a distinct C-terminus, compared to variant 1.
      Source sequence(s)
      AL160471, BC025415, BM971258, Z29433
      Consensus CDS
      CCDS45110.1
      UniProtKB/Swiss-Prot
      P30793
      Related
      ENSP00000445246.2, ENST00000536224.2
      Conserved Domains (1) summary
      cl00263
      Location:66209
      TFold; Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p12 Primary Assembly

      Range
      54842005..54902824 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017021218.1XP_016876707.1  GTP cyclohydrolase 1 isoform X1

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