Human Gene GCH1 (uc001xbk.1)
  Description: Homo sapiens GTP cyclohydrolase 1 (GCH1), transcript variant 4, mRNA.
RefSeq Summary (NM_001024071): 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].
Transcript (Including UTRs)
   Position: hg19 chr14:55,308,724-55,369,542 Size: 60,819 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg19 chr14:55,309,757-55,369,381 Size: 59,625 Coding Exon Count: 6 

Page IndexSequence and LinksPrimersGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
mRNA DescriptionsPathwaysOther NamesGeneReviewsModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr14:55,308,724-55,369,542)mRNA (may differ from genome)Protein (213 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMalacardsMGI
OMIMPubMedReactomeTreefamUniProtKBWikipedia
BioGrid CRISPR DB

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GCH1
CDC HuGE Published Literature: GCH1
Positive Disease Associations: Arthritis, Rheumatoid , broad range of clinical presentations
Related Studies:
  1. Arthritis, Rheumatoid
    Yukinori Okada et al. Nature genetics 2012, Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population., Nature genetics. [PubMed 22446963]
  2. broad range of clinical presentations
    Markova ED et al. 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., European journal of neurology. 1999 Sep;6(5):605-8. [PubMed 10457396]

-  MalaCards Disease Associations
  MalaCards Gene Search: GCH1
Diseases sorted by gene-association score: hyperphenylalaninemia, bh4-deficient, b* (1692), dystonia, dopa-responsive, with or without hyperphenylalaninemia* (1227), segawa syndrome, recessive* (283), gtp cyclohydrolase 1-deficient dopa-responsive dystonia* (100), gtp cyclohydrolase 1-related disorders* (100), dystonia (36), hyperphenylalaninemia (34), tetrahydrobiopterin deficiency (28), hereditary dystonia (27), oromandibular dystonia (23), movement disease (13), tyrosine hydroxylase deficiency (12), cervical dystonia (12), dystonia-1, torsion (11), dystonia-12 (9), non-gestational choriocarcinoma (9), phenylketonuria (8), segmental dystonia (8), dystonia-11, myoclonic (8), early-onset generalized dystonia (7), dystonia-parkinsonism, x-linked (7), blepharospasm (5), thiamine metabolism dysfunction syndrome 2 (5), degenerative disc disease (5), somatoform disorder (5), leukodystrophy, hypomyelinating, 2 (5), cranio-facial dystonia (5), meige syndrome (5), vitiligo-associated multiple autoimmune disease susceptibility 1 (5), hemidystonia (5), oculogyric crisis (4), gliosarcoma (3), parkinson disease, late-onset (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 29.79 RPKM in Liver
Total median expression: 202.87 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -72.90161-0.453 Picture PostScript Text
3' UTR -235.671033-0.228 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  Pfam Domains:
PF01227 - GTP cyclohydrolase I

SCOP Domains:
55620 - Tetrahydrobiopterin biosynthesis enzymes-like

ModBase Predicted Comparative 3D Structure on P30793-2
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Descriptions from all associated GenBank mRNAs
  U66095 - Homo sapiens cell-line THP-1 GTP cyclohydrolase I mRNA, complete cds.
U66097 - Homo sapiens cell-line THP-1 GTP cyclohydrolase I mRNA, complete cds.
BC025415 - Homo sapiens GTP cyclohydrolase 1, mRNA (cDNA clone MGC:12737 IMAGE:4129035), complete cds.
U19523 - Human GTP cyclohydrolase I mRNA, complete cds.
Z29433 - Homo sapiens mRNA for GTP cyclohydrase I, clone 1.
S44053 - GTP cyclohydrolase I {alternatively spliced, clone hGCH-2} [human, liver, mRNA, 994 nt].
AF321276 - Homo sapiens GTP cyclohydrolase I mRNA, partial cds.
AY137463 - Homo sapiens GTP cyclohydrolase I type IV mRNA, partial cds; alternatively spliced.
AY137464 - Homo sapiens GTP cyclohydrolase I type V mRNA, partial cds; alternatively spliced.
AY137465 - Homo sapiens GTP cyclohydrolase I type VI mRNA, partial cds; alternatively spliced.
S44049 - GTP cyclohydrolase I {clone hGCH-1} [human, liver, mRNA, 1180 nt].
Z29434 - Homo sapiens mRNA for GTP cyclohydrase I, clone 2.
CR536551 - Homo sapiens full open reading frame cDNA clone RZPDo834G0222D for gene GCH1, GTP cyclohydrolase 1 (dopa-responsive dystonia); complete cds, incl. stopcodon.
DQ892998 - Synthetic construct clone IMAGE:100005628; FLH191518.01X; RZPDo839E0277D GTP cyclohydrolase 1 (dopa-responsive dystonia) (GCH1) gene, encodes complete protein.
DQ896245 - Synthetic construct Homo sapiens clone IMAGE:100010705; FLH191514.01L; RZPDo839E0267D GTP cyclohydrolase 1 (dopa-responsive dystonia) (GCH1) gene, encodes complete protein.
Z16418 - Homo sapiens mRNA for GTP cyclohydrolase I.
S43856 - GTP cyclohydrolase I {clone hGCH-3} [human, liver, mRNA, 819 nt].
JD563028 - Sequence 544052 from Patent EP1572962.
JD110657 - Sequence 91681 from Patent EP1572962.
JD047001 - Sequence 28025 from Patent EP1572962.
JD262826 - Sequence 243850 from Patent EP1572962.
JD088759 - Sequence 69783 from Patent EP1572962.
JD499469 - Sequence 480493 from Patent EP1572962.
JD119947 - Sequence 100971 from Patent EP1572962.
JD173666 - Sequence 154690 from Patent EP1572962.
JD374094 - Sequence 355118 from Patent EP1572962.
JD250704 - Sequence 231728 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00790 - Folate biosynthesis
hsa01100 - Metabolic pathways

Reactome (by CSHL, EBI, and GO)

Protein P30793 (Reactome details) participates in the following event(s):

R-HSA-1474158 GCHFR binds to GCH1 and negatively regulates its activity
R-HSA-1474146 GCH1 reduces GTP to dihydroneopterin triphosphate
R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-8978934 Metabolism of cofactors
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: DYT5, GCH, NM_001024071, NP_001019242, P30793-2
UCSC ID: uc001xbk.1
RefSeq Accession: NM_001024071
Protein: P30793-2, splice isoform of P30793 CCDS: CCDS45110.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene GCH1:
drd (GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia)
dystonia-ov (Hereditary Dystonia Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001024071.1
exon count: 6CDS single in 3' UTR: no RNA size: 1852
ORF size: 642CDS single in intron: no Alignment % ID: 99.95
txCdsPredict score: 1484.00frame shift in genome: no % Coverage: 99.14
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.