Gene: GCH1

Alternate names for this Gene: DYT14|DYT5|DYT5a|GCH|GTP-CH-1|GTPCH1|HPABH4B

Gene 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.

Gene is located in Chromosome: 14

Location in Chromosome : 14q22.2

Description of this Gene: GTP cyclohydrolase 1

Type of Gene: protein-coding

rs104894433 in GCH1 gene and Dopa-Responsive Dystonia PMID 7874165 1994 Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.

PMID 10825351 2000 Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations?

PMID 10582612 1999 Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I: relationship to etiology of dopa-responsive dystonia.

PMID 9120469 1997 A novel point mutation in the GTP cyclohydrolase I gene in a Spanish family with hereditary progressive and dopa responsive dystonia.

PMID 8957022 1996 Mutant GTP cyclohydrolase I mRNA levels contribute to dopa-responsive dystonia onset.

PMID 17101830 2006 Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia.

PMID 10076897 1999 A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive dystonia.

PMID 9778264 1998 Dopa-responsive dystonia: a clinical and molecular genetic study.

PMID 8852666 1996 Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity.

PMID 7501255 1995 GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation.

PMID 10208576 1999 A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form.

PMID 10987649 1999 Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation.

PMID 20482602 2011 EFNS guidelines on diagnosis and treatment of primary dystonias.

PMID 11113234 2000 Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. German Dystonia Study Group.

PMID 9328244 1997 GTP cyclohydrolase I mutations in patients with dystonia responsive to anticholinergic drugs.

PMID 12391354 2002 Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome.

PMID 17898029 2008 Frequency of GCH1 deletions in Dopa-responsive dystonia.

PMID 16917893 2006 Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase.

PMID 9667588 1998 Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations.

PMID 15753436 2005 High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening.

PMID 15303002 2004 GTP-cyclohydrolase I gene mutations in patients with autosomal dominant and recessive GTP-CH1 deficiency: identification and functional characterization of four novel mutations.

PMID 20842687 2011 Severe dystonic encephalopathy without hyperphenylalaninemia associated with an 18-bp deletion within the proximal GCH1 promoter.

PMID 10496263 1999 Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia.

PMID 9749603 1998 Dominant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia.

PMID 19491146 2009 Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.

PMID 8619546 1996 GTP-cyclohydrolase I gene mutations in hereditary progressive amd dopa-responsive dystonia.

PMID 10457396 1999 A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia.

PMID 20082337 2010 High frequency of multiexonic deletion of the GCH1 gene in a Taiwanese cohort of dopa-response dystonia.

PMID 19332422 2009 Autosomal-dominant GTPCH1-deficient DRD: clinical characteristics and long-term outcome of 34 patients.

PMID 20108370 2010 GCH1 mutation and clinical study of Chinese patients with dopa-responsive dystonia.

PMID 20491893 2011 A novel missense mutation in GTP cyclohydrolase I (GCH1) gene causes Dopa-responsive dystonia in Chinese Han population.

PMID 10984670 2000 Missense mutants inactivate guanosine triphosphate cyclohydrolase I in hereditary progressive dystonia.

PMID 23211702 2013 Two novel mutations of the GTP cyclohydrolase 1 gene and genotype-phenotype correlation in Chinese Dopa-responsive dystonia patients.

PMID 11486899 2001 A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping.

rs10149080 in GCH1 gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs104894434 in GCH1 gene and Hyperphenylalaninemia, BH4-Deficient, B PMID 7501255 1995 GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation.

PMID 9667588 1998 Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations.

PMID 16917893 2006 Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase.

PMID 17898029 2008 Frequency of GCH1 deletions in Dopa-responsive dystonia.

PMID 15753436 2005 High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening.

PMID 27246466 2017 Four Years of Diagnostic Challenges with Tetrahydrobiopterin Deficiencies in Iranian Patients.

PMID 20842687 2011 Severe dystonic encephalopathy without hyperphenylalaninemia associated with an 18-bp deletion within the proximal GCH1 promoter.

PMID 15303002 2004 GTP-cyclohydrolase I gene mutations in patients with autosomal dominant and recessive GTP-CH1 deficiency: identification and functional characterization of four novel mutations.

PMID 10496263 1999 Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia.

PMID 17101830 2006 Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia.

PMID 19491146 2009 Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.

PMID 9749603 1998 Dominant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia.

PMID 8619546 1996 GTP-cyclohydrolase I gene mutations in hereditary progressive amd dopa-responsive dystonia.

PMID 10457396 1999 A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia.

PMID 11486899 2001 A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping.

PMID 23211702 2013 Two novel mutations of the GTP cyclohydrolase 1 gene and genotype-phenotype correlation in Chinese Dopa-responsive dystonia patients.

PMID 20082337 2010 High frequency of multiexonic deletion of the GCH1 gene in a Taiwanese cohort of dopa-response dystonia.

PMID 20108370 2010 GCH1 mutation and clinical study of Chinese patients with dopa-responsive dystonia.

PMID 10984670 2000 Missense mutants inactivate guanosine triphosphate cyclohydrolase I in hereditary progressive dystonia.

PMID 8852666 1996 Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity.

PMID 19332422 2009 Autosomal-dominant GTPCH1-deficient DRD: clinical characteristics and long-term outcome of 34 patients.

PMID 20491893 2011 A novel missense mutation in GTP cyclohydrolase I (GCH1) gene causes Dopa-responsive dystonia in Chinese Han population.

rs11158026 in GCH1 gene and Parkinson Disease PMID 25064009 2014 Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

PMID 28892059 2017 A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.

PMID 27182965 2016 Detection and interpretation of shared genetic influences on 42 human traits.

rs3783637 in GCH1 gene and Polysomnography PMID 23251661 2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.

rs10131232 in GCH1 gene and Protein measurement PMID 23056639 2012 A genome-wide association study of circulating galectin-3.

rs10149080 in GCH1 gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.