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GCH1 GTP cyclohydrolase 1 [ Homo sapiens (human) ]

Gene ID: 2643, updated on 6-Jan-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 cyclohydrolase I activity TAS
Traceable Author Statement
more info
 
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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