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
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]
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]
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.
ModBase Predicted Comparative 3D Structure on P30793-2
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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.
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