Gch1 (GTP cyclohydrolase 1) - Rat Genome Database

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Gene: Gch1 (GTP cyclohydrolase 1) Rattus norvegicus
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Symbol: Gch1
Name: GTP cyclohydrolase 1
RGD ID: 61992
Description: Enables several functions, including GTP binding activity; GTP cyclohydrolase I activity; and metal ion binding activity. Involved in several processes, including dihydrobiopterin metabolic process; negative regulation of cellular senescence; and regulation of apoptotic process. Located in mitochondrion and nucleus. Part of intracellular protein-containing complex. Used to study Parkinsonism; cerebral infarction; hypertension; myocardial infarction; and transient cerebral ischemia. Biomarker of several diseases, including artery disease (multiple); liver disease (multiple); middle cerebral artery infarction; pulmonary fibrosis; and sciatic neuropathy. Human ortholog(s) of this gene implicated in several diseases, including BH4-deficient hyperphenylalaninemia B; diabetic angiopathy; movement disease (multiple); sickle cell anemia; and type 2 diabetes mellitus. Orthologous to human GCH1 (GTP cyclohydrolase 1); PARTICIPATES IN dopa responsive dystonia pathway; Segawa syndrome pathway; folate metabolic pathway; INTERACTS WITH 1,2,4-trimethylbenzene; 17alpha-ethynylestradiol; 17beta-estradiol.
Type: protein-coding
RefSeq Status: PROVISIONAL
Previously known as: Gch; GTP cyclohydrase I; GTP cyclohydrolase I; GTP-CH-I; GTPCH; GTPCH-1
RGD Orthologs
Human
Mouse
Chinchilla
Bonobo
Dog
Squirrel
Pig
Green Monkey
Naked Mole-Rat
Black Rat
Alliance Orthologs
More Info more info ...
Latest Assembly: GRCr8 - GRCr8 Assembly
Position:
Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCr81522,884,006 - 22,917,412 (-)NCBIGRCr8GRCr8GRCr8
GRCr8 Ensembl1522,884,006 - 22,917,412 (-)EnsemblGRCr8
mRatBN7.21520,404,267 - 20,437,727 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)EnsemblmRatBN7.2
UTH_Rnor_SHR_Utx1523,184,907 - 23,218,319 (-)NCBIUTH_Rnor_SHR_UtxUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01524,142,871 - 24,176,283 (-)NCBIUTH_Rnor_SHRSP_BbbUtx_1.0UTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01522,394,011 - 22,427,378 (-)NCBIUTH_Rnor_WKY_Bbb_1.0UTH_Rnor_WKY_Bbb_1.0
Rnor_6.01523,935,011 - 23,968,971 (-)NCBIRnor_6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1523,934,585 - 23,969,011 (-)Ensemblrn6Rnor6.0
Rnor_5.01527,876,253 - 27,910,213 (-)NCBIRnor_5.0Rnor_5.0rn5
RGSC_v3.41523,023,996 - 23,139,794 (-)NCBIRGSC_v3.4RGSC_v3.4rn4
Celera1520,799,206 - 20,832,598 (-)NCBICelera
RGSC_v3.11523,039,695 - 23,155,494 (-)NCBI
Cytogenetic Map15p14NCBI
JBrowse:




Gene-Chemical Interaction Annotations     Click to see Annotation Detail View
(1->4)-beta-D-glucan  (ISO)
(S)-colchicine  (ISO)
(S)-nicotine  (ISO)
1,1-dichloroethene  (ISO)
1,2,4-trimethylbenzene  (EXP)
1,2-dichloroethane  (ISO)
1,2-dimethylhydrazine  (ISO)
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine  (ISO)
17alpha-ethynylestradiol  (EXP)
17beta-estradiol  (EXP,ISO)
17beta-estradiol 3-benzoate  (EXP)
2,3,7,8-tetrachlorodibenzodioxine  (EXP,ISO)
2,4,6-trinitrobenzenesulfonic acid  (ISO)
2,4-diaminotoluene  (ISO)
2,4-dibromophenyl 2,4,5-tribromophenyl ether  (ISO)
2,4-dinitrotoluene  (EXP)
2,6-dinitrotoluene  (EXP)
2-butoxyethanol  (ISO)
2-methylcholine  (ISO)
3',5'-cyclic GMP  (ISO)
3,3',5-triiodo-L-thyronine  (EXP)
3-methylcholanthrene  (ISO)
4,4'-sulfonyldiphenol  (ISO)
4-hydroxyphenyl retinamide  (ISO)
5,6,7,8-tetrahydrobiopterin  (ISO)
5-aza-2'-deoxycytidine  (ISO)
6-propyl-2-thiouracil  (EXP)
acetylcholine  (EXP,ISO)
acrolein  (ISO)
acrylamide  (ISO)
actinomycin D  (ISO)
adenine  (ISO)
aldehydo-D-glucose  (ISO)
all-trans-retinoic acid  (ISO)
alpha-pinene  (ISO)
amitrole  (EXP)
ammonium chloride  (EXP)
anthra[1,9-cd]pyrazol-6(2H)-one  (ISO)
antimycin A  (ISO)
antirheumatic drug  (ISO)
aristolochic acid A  (ISO)
arsane  (ISO)
arsenic atom  (ISO)
arsenite(3-)  (ISO)
benzo[a]pyrene  (ISO)
benzo[a]pyrene diol epoxide I  (ISO)
benzo[b]fluoranthene  (ISO)
bisphenol A  (EXP,ISO)
bisphenol F  (ISO)
butanal  (ISO)
cadmium atom  (ISO)
cadmium dichloride  (EXP,ISO)
Calcimycin  (EXP)
camptothecin  (ISO)
capsaicin  (ISO)
carbon nanotube  (ISO)
chrysene  (ISO)
cisplatin  (ISO)
clofibrate  (ISO)
cobalt dichloride  (EXP)
copper atom  (EXP)
copper(0)  (EXP)
copper(II) sulfate  (ISO)
cordycepin  (ISO)
cyclosporin A  (ISO)
cyproconazole  (ISO)
D-glucose  (ISO)
decabromodiphenyl ether  (EXP)
dexamethasone  (EXP)
diazinon  (EXP,ISO)
dicrotophos  (ISO)
diethylstilbestrol  (EXP)
dimethylarsinic acid  (ISO)
dioxygen  (ISO)
dopamine  (EXP)
dorsomorphin  (ISO)
endosulfan  (EXP)
epoxiconazole  (ISO)
ethyl methanesulfonate  (ISO)
flavonoids  (EXP)
fluoranthene  (ISO)
flutamide  (EXP)
folic acid  (ISO)
formaldehyde  (ISO)
fulvestrant  (EXP)
furan  (EXP)
gentamycin  (EXP)
glucose  (ISO)
glutathione  (EXP)
glyphosate  (ISO)
GW 501516  (ISO)
hydrogen peroxide  (ISO)
inulin  (ISO)
L-erythro-7,8-dihydrobiopterin  (ISO)
lead diacetate  (EXP,ISO)
lipopolysaccharide  (EXP,ISO)
manganese(II) chloride  (EXP)
methamphetamine  (EXP)
methidathion  (ISO)
methotrexate  (ISO)
methyl methanesulfonate  (ISO)
methylarsonic acid  (ISO)
methylmercury chloride  (ISO)
methylphenidate  (ISO)
mitomycin C  (ISO)
mitoxantrone  (ISO)
N-nitrosodiethylamine  (EXP)
naphthalenes  (EXP)
nefazodone  (EXP)
neopterin  (ISO)
nickel atom  (ISO)
nickel dichloride  (EXP)
nicotine  (ISO)
nimesulide  (EXP)
Nutlin-3  (ISO)
okadaic acid  (ISO)
oxaliplatin  (EXP)
oxidopamine  (EXP)
ozone  (ISO)
paracetamol  (EXP,ISO)
paraquat  (EXP)
parathion  (ISO)
perfluorooctane-1-sulfonic acid  (ISO)
perfluorooctanoic acid  (EXP)
phenethyl caffeate  (EXP)
phenobarbital  (EXP,ISO)
pirinixic acid  (ISO)
pregnenolone 16alpha-carbonitrile  (EXP)
profenofos  (EXP)
propiconazole  (ISO)
reserpine  (EXP)
resveratrol  (EXP,ISO)
rotenone  (EXP,ISO)
S-(1,2-dichlorovinyl)-L-cysteine  (ISO)
sapropterin  (ISO)
sarin  (ISO)
SB 431542  (ISO)
sepiapterin  (EXP)
sevoflurane  (EXP)
silicon dioxide  (EXP,ISO)
silver atom  (ISO)
silver(0)  (ISO)
sodium arsenate  (ISO)
sodium arsenite  (ISO)
sodium dichromate  (EXP,ISO)
Soman  (EXP)
succimer  (ISO)
sulfadimethoxine  (EXP)
sunitinib  (ISO)
superoxide  (ISO)
testosterone  (EXP,ISO)
tetrachloromethane  (ISO)
thioacetamide  (EXP)
titanium dioxide  (EXP,ISO)
topotecan  (EXP,ISO)
Tributyltin oxide  (ISO)
trichostatin A  (ISO)
triptonide  (ISO)
undecane  (EXP)
urethane  (ISO)
valproic acid  (ISO)
vinclozolin  (EXP)
VX nerve agent  (ISO)
zinc atom  (ISO)
zinc(0)  (ISO)

Gene Ontology Annotations     Click to see Annotation Detail View

Cellular Component

Molecular Pathway Annotations     Click to see Annotation Detail View
References

References - curated
# Reference Title Reference Citation
1. Role of tetrahydrobiopterin in pulmonary vascular remodelling associated with pulmonary fibrosis. Almudéver P, etal., Thorax. 2013 Oct;68(10):938-48. doi: 10.1136/thoraxjnl-2013-203408. Epub 2013 Jun 5.
2. Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status. Asensio Lopez MDC, etal., Sci Rep. 2020 Aug 11;10(1):13553. doi: 10.1038/s41598-020-70454-8.
3. Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease. Azzouz M, etal., J Neurosci 2002 Dec 1;22(23):10302-12.
4. Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats. Baotic I, etal., Anesthesiology. 2015 Sep;123(3):582-9. doi: 10.1097/ALN.0000000000000778.
5. A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia. Belfer I, etal., Am J Hematol. 2014 Feb;89(2):187-93. doi: 10.1002/ajh.23613.
6. Evidence of a role for GTP cyclohydrolase-1 in visceral pain. Bulmer DC, etal., Neurogastroenterol Motil. 2015 May;27(5):656-62. doi: 10.1111/nmo.12538. Epub 2015 Mar 17.
7. Inhibition of tetrahydrobiopterin synthesis reduces in vivo nitric oxide production in experimental endotoxic shock. Bune AJ, etal., Biochem Biophys Res Commun. 1996 Mar 7;220(1):13-9. doi: 10.1006/bbrc.1996.0348.
8. Controlled Striatal DOPA Production From a Gene Delivery System in a Rodent Model of Parkinson's Disease. Cederfjäll E, etal., Mol Ther. 2015 May;23(5):896-906. doi: 10.1038/mt.2015.8. Epub 2015 Jan 16.
9. Continuous DOPA synthesis from a single AAV: dosing and efficacy in models of Parkinson's disease. Cederfjäll E, etal., Sci Rep. 2013;3:2157. doi: 10.1038/srep02157.
10. Pharmacological inhibition of guanosine triphosphate cyclohydrolase1 elevates tyrosine phosphorylation of caveolin1 and cellular senescence. Charles S, etal., Eur J Pharmacol. 2019 Apr 5;848:1-10. doi: 10.1016/j.ejphar.2019.01.036. Epub 2019 Jan 25.
11. Limb remote ischemic post-conditioning reduces brain reperfusion injury by reversing eNOS uncoupling. Chen G, etal., Indian J Exp Biol. 2014 Jun;52(6):597-605.
12. Sodium Tanshinone IIA sulfonate improves post-ischemic angiogenesis in hyperglycemia. Chen L, etal., Biochem Biophys Res Commun. 2019 Dec 10;520(3):580-585. doi: 10.1016/j.bbrc.2019.09.106. Epub 2019 Oct 14.
13. Blockade of tetrahydrobiopterin synthesis protects neurons after transient forebrain ischemia in rat: a novel role for the cofactor. Cho S, etal., J Neurosci. 1999 Feb 1;19(3):878-89. doi: 10.1523/JNEUROSCI.19-03-00878.1999.
14. The protein partners of GTP cyclohydrolase I in rat organs. Du J, etal., PLoS One. 2012;7(3):e33991. doi: 10.1371/journal.pone.0033991. Epub 2012 Mar 27.
15. Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet. Ezrokhi M, etal., Int J Mol Sci. 2021 Jun 7;22(11):6142. doi: 10.3390/ijms22116142.
16. GTP cyclohydrolase I induction in striatal astrocytes following intrastriatal kainic acid lesion. Foster JA, etal., J Chem Neuroanat 2002 Sep;24(3):173-9.
17. Possible involvement of tetrahydrobiopterin in the disturbance of redox homeostasis in sepsis - Induced brain dysfunction. Gamal M, etal., Brain Res. 2018 Apr 15;1685:19-28. doi: 10.1016/j.brainres.2018.02.008. Epub 2018 Feb 9.
18. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Gaudet P, etal., Brief Bioinform. 2011 Sep;12(5):449-62. doi: 10.1093/bib/bbr042. Epub 2011 Aug 27.
19. Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The first enzyme of the tetrahydrobiopterin biosynthetic pathway. Hatakeyama K, etal., J Biol Chem 1991 Jan 15;266(2):765-9.
20. Purification and characterization of rat liver GTP cyclohydrolase I. Cooperative binding of GTP to the enzyme. Hatakeyama K, etal., J Biol Chem. 1989 Dec 25;264(36):21660-4.
21. Glucocorticoid regulation of nitric oxide and tetrahydrobiopterin in a rat model of endotoxic shock. Hattori Y, etal., Biochem Biophys Res Commun. 1997 Nov 17;240(2):298-303. doi: 10.1006/bbrc.1997.7653.
22. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Ichinose H, etal., Nat Genet. 1994 Nov;8(3):236-42.
23. Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase I in PC12 cells. Imazumi K, etal., Biochem Biophys Res Commun. 1994 Dec 15;205(2):1409-16.
24. Linkage and candidate gene analysis of 14q22-24 in bipolar disorder: support for GCHI as a novel susceptibility gene. Kealey C, etal., Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136(1):75-80.
25. KEGG: Kyoto Encyclopedia of Genes and Genomes KEGG
26. Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates cerebral infarction via reducing inducible NO synthase and peroxynitrite in ischemic stroke. Kidd GA, etal., Stroke. 2005 Dec;36(12):2705-11. doi: 10.1161/01.STR.0000190000.98707.6d. Epub 2005 Nov 10.
27. Effective relief of neuropathic pain by adeno-associated virus-mediated expression of a small hairpin RNA against GTP cyclohydrolase 1. Kim SJ, etal., Mol Pain. 2009 Nov 18;5:67. doi: 10.1186/1744-8069-5-67.
28. Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease. Kim SU, etal., Neuropathology. 2006 Apr;26(2):129-40. doi: 10.1111/j.1440-1789.2006.00688.x.
29. The mechanism of potent GTP cyclohydrolase I inhibition by 2,4-diamino-6-hydroxypyrimidine: requirement of the GTP cyclohydrolase I feedback regulatory protein. Kolinsky MA and Gross SS, J Biol Chem. 2004 Sep 24;279(39):40677-82. Epub 2004 Jul 29.
30. Coinduction of GTP cyclohydrolase I and inducible NO synthase in rat osteoblasts during space flight: apoptotic and self-protective response? Kumei Y, etal., Ann N Y Acad Sci. 2003 Dec;1010:481-5.
31. Increased blood flow causes coordinated upregulation of arterial eNOS and biosynthesis of tetrahydrobiopterin. Lam CF, etal., Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H786-93. Epub 2005 Sep 30.
32. Pre-treatment of acupuncture stimulation of ST36 (Zusanli) significantly attenuates CAT-2, CAT-2B and GTPCH transcription in septic rat lungs. Lao HC, etal., Acta Anaesthesiol Taiwan. 2006 Jun;44(2):83-91.
33. Administration of a low dose of sildenafil for 1 week decreases intrahepatic resistance in rats with biliary cirrhosis: the role of NO bioavailability. Lee KC, etal., Clin Sci (Lond). 2010 Apr 7;119(1):45-55. doi: 10.1042/CS20090601.
34. Effect of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats. Li HY, etal., Crit Care Med. 2002 Nov;30(11):2520-7. doi: 10.1097/00003246-200211000-00020.
35. Association of a functional polymorphism (C59038T) in GTP cyclohydrolase 1 gene and Type 2 diabetic macrovascular disease in the Chinese population. Liao YF, etal., J Diabetes Complications. 2010 Sep-Oct;24(5):313-9. doi: 10.1016/j.jdiacomp.2009.04.003. Epub 2009 Jun 9.
36. Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP, its feedback regulatory protein. Maita N, etal., J Biol Chem. 2004 Dec 3;279(49):51534-40. Epub 2004 Sep 23.
37. Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP. Maita N, etal., Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1212-7. Epub 2002 Jan 29.
38. The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis. Matei V, etal., Hepatology. 2006 Jul;44(1):44-52. doi: 10.1002/hep.21228.
39. Changes of GTP cyclohydrolase I and neuronal apoptosis in rat spinal dorsal cord induced by sciatic nerve injury. Meng C, etal., Neurol Sci. 2013 Dec;34(12):2145-50. doi: 10.1007/s10072-013-1353-5. Epub 2013 Mar 21.
40. Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP. Milstien S, etal., J Biol Chem 1996 Aug 16;271(33):19743-51.
41. GTP cyclohydrolase 1 inhibition attenuates vasodilation and increases blood pressure in rats. Mitchell BM, etal., Am J Physiol Heart Circ Physiol. 2003 Nov;285(5):H2165-70. Epub 2003 Jul 10.
42. GTP cyclohydrolase 1 downregulation contributes to glucocorticoid hypertension in rats. Mitchell BM, etal., Hypertension. 2003 Mar;41(3 Pt 2):669-74. doi: 10.1161/01.HYP.0000051889.62249.5D. Epub 2003 Jan 13.
43. Phenylalanine improves dilation and blood pressure in GTP cyclohydrolase inhibition-induced hypertensive rats. Mitchell BM, etal., J Cardiovasc Pharmacol. 2004 Jun;43(6):758-63. doi: 10.1097/00005344-200406000-00004.
44. Electronic Transfer of LocusLink and RefSeq Data NCBI rat LocusLink and RefSeq merged data July 26, 2002
45. Dopa responsive dystonia with Turner's syndrome: clinical, genetic, and neuropsychological studies in a family with a new mutation in the GTP-cyclohydrolase I gene. Nitschke M, etal., J Neurol Neurosurg Psychiatry. 1998 Jun;64(6):806-8. doi: 10.1136/jnnp.64.6.806.
46. Suppressed expression of GTP cyclohydrolase I mRNA and accelerated expression of inducible nitric oxide synthase mRNA in endomyocardial biopsy specimens from patients with dilated cardiomyopathy. Ohtsuki M, etal., Clin Chim Acta. 2005 Mar;353(1-2):103-7. doi: 10.1016/j.cccn.2004.10.004.
47. OMIM Disease Annotation Pipeline OMIM Disease Annotation Pipeline
48. KEGG Annotation Import Pipeline Pipeline to import KEGG annotations from KEGG into RGD
49. SMPDB Annotation Import Pipeline Pipeline to import SMPDB annotations from SMPDB into RGD
50. GOA pipeline RGD automated data pipeline
51. ClinVar Automated Import and Annotation Pipeline RGD automated import pipeline for ClinVar variants, variant-to-disease annotations and gene-to-disease annotations
52. Data Import for Chemical-Gene Interactions RGD automated import pipeline for gene-chemical interactions
53. Comprehensive gene review and curation RGD comprehensive gene curation
54. Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy. Satoh M, etal., Nephrol Dial Transplant. 2008 Dec;23(12):3806-13. doi: 10.1093/ndt/gfn357. Epub 2008 Jul 2.
55. Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration. Serova LI, etal., Brain Res. 2004 Jul 23;1015(1-2):1-8.
56. Exercise training augments neuronal nitric oxide synthase dimerization in the paraventricular nucleus of rats with chronic heart failure. Sharma NM, etal., Nitric Oxide. 2019 Jun 1;87:73-82. doi: 10.1016/j.niox.2019.03.005. Epub 2019 Mar 13.
57. Rat GTP cyclohydrolase I is a homodecameric protein complex containing high-affinity calcium-binding sites. Steinmetz MO, etal., J Mol Biol. 1998 May 29;279(1):189-99.
58. Coexpression of tyrosine hydroxylase, GTP cyclohydrolase I, aromatic amino acid decarboxylase, and vesicular monoamine transporter 2 from a helper virus-free herpes simplex virus type 1 vector supports high-level, long-term biochemical and behavioral correction of a rat model of Parkinson's disease. Sun M, etal., Hum Gene Ther. 2004 Dec;15(12):1177-96.
59. Enhanced expression of GTP cyclohydrolase I in V-1-overexpressing PC12D cells. Suzuki T, etal., Biochem Biophys Res Commun 2002 May 10;293(3):962-8.
60. GTP cyclohydrolase 1 gene 3'-UTR C+243T variant predicts worsening outcome in patients with first-onset ischemic stroke. Tang L, etal., J Huazhong Univ Sci Technolog Med Sci. 2010 Dec;30(6):694-8. doi: 10.1007/s11596-010-0642-y. Epub 2010 Dec 22.
61. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Tegeder I, etal., Nat Med. 2006 Nov;12(11):1269-77. Epub 2006 Oct 22.
62. Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome. Umman B, etal., Gene. 2015 Dec 10;574(1):76-81. doi: 10.1016/j.gene.2015.07.081. Epub 2015 Jul 30.
63. L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4. Wang Z, etal., PLoS One. 2021 Apr 15;16(4):e0250126. doi: 10.1371/journal.pone.0250126. eCollection 2021.
64. Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus. Wenzel P, etal., Atherosclerosis. 2008 May;198(1):65-76. Epub 2007 Dec 3.
65. Induction of GTP cyclohydrolase I by bacterial lipopolysaccharide in the rat. Werner-Felmayer G, etal., FEBS Lett. 1993 May 17;322(3):223-6.
66. Bacterial translocation up-regulates GTP-cyclohydrolase I in mesenteric vasculature of cirrhotic rats. Wiest R, etal., Hepatology. 2003 Dec;38(6):1508-15. doi: 10.1016/j.hep.2003.09.039.
67. GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus. Wolkow PP, etal., PLoS One. 2014 Nov 4;9(11):e108587. doi: 10.1371/journal.pone.0108587. eCollection 2014.
68. Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy. Wu HE, etal., Sci Rep. 2016 Jun 13;6:27925. doi: 10.1038/srep27925.
69. Polymorphisms of genes in nitric oxide-forming pathway associated with ischemic stroke in Chinese Han population. Yan JT, etal., Acta Pharmacol Sin. 2011 Nov;32(11):1357-63. doi: 10.1038/aps.2011.114. Epub 2011 Oct 3.
70. Ionizing radiation induces BH4 deficiency by downregulating GTP-cyclohydrolase 1, a novel target for preventing and treating radiation enteritis. Yan T, etal., Biochem Pharmacol. 2020 Oct;180:114102. doi: 10.1016/j.bcp.2020.114102. Epub 2020 Jun 17.
71. Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH4/eNOS to Improve Intestinal Ischemia. Yan T, etal., Front Pharmacol. 2021 Apr 22;12:629125. doi: 10.3389/fphar.2021.629125. eCollection 2021.
72. Decameric GTP cyclohydrolase I forms complexes with two pentameric GTP cyclohydrolase I feedback regulatory proteins in the presence of phenylalanine or of a combination of tetrahydrobiopterin and GTP. Yoneyama T and Hatakeyama K, J Biol Chem. 1998 Aug 7;273(32):20102-8.
73. MiR-124 inhibits spinal neuronal apoptosis through binding to GCH1. Yuan S, etal., Eur Rev Med Pharmacol Sci. 2019 Jun;23(11):4564-4574. doi: 10.26355/eurrev_201906_18032.
74. Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk. Zhang L, etal., J Clin Invest. 2007 Sep;117(9):2658-71. doi: 10.1172/JCI31093.
75. COX-2/sEH Dual Inhibitor PTUPB Alleviates CCl 4 -Induced Liver Fibrosis and Portal Hypertension. Zhao Z, etal., Front Med (Lausanne). 2021 Dec 23;8:761517. doi: 10.3389/fmed.2021.761517. eCollection 2021.
76. Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertension. Zheng JS, etal., Circulation. 2003 Sep 9;108(10):1238-45. doi: 10.1161/01.CIR.0000089082.40285.C3. Epub 2003 Aug 18.
Additional References at PubMed
PMID:2463916   PMID:3318829   PMID:3753653   PMID:7524491   PMID:7678411   PMID:7730309   PMID:8068008   PMID:9092499   PMID:9445252   PMID:10907721   PMID:11087823   PMID:11087827  
PMID:11284739   PMID:12176133   PMID:12607127   PMID:12716655   PMID:14717702   PMID:15604419   PMID:15721862   PMID:15824199   PMID:16000090   PMID:16338639   PMID:16696853   PMID:16778797  
PMID:17101830   PMID:18004997   PMID:19294699   PMID:19666465   PMID:19762783   PMID:21163945   PMID:25557619   PMID:28399119   PMID:36908807  


Genomics

Comparative Map Data
Gch1
(Rattus norvegicus - Norway rat)
Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCr81522,884,006 - 22,917,412 (-)NCBIGRCr8GRCr8GRCr8
GRCr8 Ensembl1522,884,006 - 22,917,412 (-)EnsemblGRCr8
mRatBN7.21520,404,267 - 20,437,727 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)EnsemblmRatBN7.2
UTH_Rnor_SHR_Utx1523,184,907 - 23,218,319 (-)NCBIUTH_Rnor_SHR_UtxUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01524,142,871 - 24,176,283 (-)NCBIUTH_Rnor_SHRSP_BbbUtx_1.0UTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01522,394,011 - 22,427,378 (-)NCBIUTH_Rnor_WKY_Bbb_1.0UTH_Rnor_WKY_Bbb_1.0
Rnor_6.01523,935,011 - 23,968,971 (-)NCBIRnor_6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1523,934,585 - 23,969,011 (-)Ensemblrn6Rnor6.0
Rnor_5.01527,876,253 - 27,910,213 (-)NCBIRnor_5.0Rnor_5.0rn5
RGSC_v3.41523,023,996 - 23,139,794 (-)NCBIRGSC_v3.4RGSC_v3.4rn4
Celera1520,799,206 - 20,832,598 (-)NCBICelera
RGSC_v3.11523,039,695 - 23,155,494 (-)NCBI
Cytogenetic Map15p14NCBI
GCH1
(Homo sapiens - human)
Human AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCh381454,842,017 - 54,902,826 (-)NCBIGRCh38GRCh38hg38GRCh38
GRCh38.p14 Ensembl1454,842,008 - 54,903,280 (-)Ensemblhg38GRCh38
GRCh371455,308,735 - 55,369,544 (-)NCBIGRCh37GRCh37hg19GRCh37
Build 361454,378,473 - 54,439,292 (-)NCBIBuild 36Build 36hg18NCBI36
Build 341454,378,484 - 54,439,279NCBI
Celera1435,358,210 - 35,419,030 (-)NCBICelera
Cytogenetic Map14q22.2NCBI
HuRef1435,471,338 - 35,532,109 (-)NCBIHuRef
CHM1_11455,247,346 - 55,308,167 (-)NCBICHM1_1
T2T-CHM13v2.01449,047,244 - 49,108,020 (-)NCBIT2T-CHM13v2.0
Gch1
(Mus musculus - house mouse)
Mouse AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCm391447,391,352 - 47,426,870 (-)NCBIGRCm39GRCm39mm39
GRCm39 Ensembl1447,391,352 - 47,426,870 (-)EnsemblGRCm39 EnsemblGRCm39
GRCm381447,153,895 - 47,189,413 (-)NCBIGRCm38GRCm38mm10GRCm38
GRCm38.p6 Ensembl1447,153,895 - 47,189,413 (-)Ensemblmm10GRCm38
MGSCv371447,773,570 - 47,809,077 (-)NCBIMGSCv37MGSCv37mm9NCBIm37
MGSCv361446,075,772 - 46,111,279 (-)NCBIMGSCv36mm8
Celera1443,334,771 - 43,370,387 (-)NCBICelera
Cytogenetic Map14C1NCBI
cM Map1424.6NCBI
Gch1
(Chinchilla lanigera - long-tailed chinchilla)
Chinchilla AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
ChiLan1.0 EnsemblNW_0049554098,624,468 - 8,668,614 (+)Ensembl
ChiLan1.0NW_0049554098,624,225 - 8,670,436 (+)NCBIChiLan1.0ChiLan1.0
GCH1
(Pan paniscus - bonobo/pygmy chimpanzee)
Bonobo AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
NHGRI_mPanPan1-v21555,932,208 - 56,026,639 (-)NCBINHGRI_mPanPan1-v2
NHGRI_mPanPan11455,179,865 - 55,240,594 (-)NCBINHGRI_mPanPan1
Mhudiblu_PPA_v01435,428,676 - 35,489,359 (-)NCBIMhudiblu_PPA_v0Mhudiblu_PPA_v0panPan3
PanPan1.11453,706,723 - 53,767,393 (-)NCBIPanPan1.1PanPan1.1panPan2
PanPan1.1 Ensembl1453,706,723 - 53,767,393 (-)EnsemblpanPan2panpan1.1
GCH1
(Canis lupus familiaris - dog)
Dog AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
CanFam3.1830,733,422 - 30,784,067 (-)NCBICanFam3.1CanFam3.1canFam3CanFam3.1
CanFam3.1 Ensembl830,732,608 - 30,784,156 (-)EnsemblcanFam3CanFam3.1
Dog10K_Boxer_Tasha830,501,844 - 30,552,428 (-)NCBIDog10K_Boxer_TashaDog10K_Boxer_Tasha
ROS_Cfam_1.0830,989,520 - 31,040,202 (-)NCBIROS_Cfam_1.0ROS_Cfam_1.0
ROS_Cfam_1.0 Ensembl830,967,731 - 31,040,294 (-)EnsemblROS_Cfam_1.0 Ensembl
UMICH_Zoey_3.1830,593,993 - 30,644,489 (-)NCBIUMICH_Zoey_3.1
UNSW_CanFamBas_1.0830,669,980 - 30,720,620 (-)NCBIUNSW_CanFamBas_1.0
UU_Cfam_GSD_1.0831,035,484 - 31,086,113 (-)NCBIUU_Cfam_GSD_1.0UU_Cfam_GSD_1.0
Gch1
(Ictidomys tridecemlineatus - thirteen-lined ground squirrel)
Squirrel AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
HiC_Itri_2NW_02440864074,457,811 - 74,501,265 (+)NCBIHiC_Itri_2
SpeTri2.0 EnsemblNW_004936697232,198 - 273,389 (+)EnsemblSpeTri2.0 Ensembl
SpeTri2.0NW_004936697232,048 - 275,420 (+)NCBISpeTri2.0SpeTri2.0SpeTri2.0
GCH1
(Sus scrofa - pig)
Pig AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
Sscrofa11.1 Ensembl1184,199,679 - 184,257,315 (-)EnsemblsusScr11Sscrofa11.1
Sscrofa11.11184,201,232 - 184,264,060 (-)NCBISscrofa11.1Sscrofa11.1susScr11Sscrofa11.1
Sscrofa10.21204,648,349 - 204,712,905 (-)NCBISscrofa10.2Sscrofa10.2susScr3
GCH1
(Chlorocebus sabaeus - green monkey)
Green Monkey AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
ChlSab1.12432,029,997 - 32,079,656 (-)NCBIChlSab1.1ChlSab1.1chlSab2
ChlSab1.1 Ensembl2432,027,648 - 32,079,490 (-)EnsemblChlSab1.1 EnsemblchlSab2Vervet-AGM
Vero_WHO_p1.0NW_02366605320,264,246 - 20,316,487 (-)NCBIVero_WHO_p1.0Vero_WHO_p1.0
Gch1
(Heterocephalus glaber - naked mole-rat)
Naked Mole-Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
HetGla_female_1.0 EnsemblNW_00462473114,459,303 - 14,500,429 (+)EnsemblHetGla_female_1.0 EnsemblhetGla2HetGla_female_1.0 Ensembl
HetGla 1.0NW_00462473114,459,164 - 14,502,485 (+)NCBIHetGla 1.0HetGla 1.0hetGla2
Gch1
(Rattus rattus - black rat)
Black Rat AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
Rrattus_CSIRO_v11275,861,953 - 75,897,122 (+)NCBIRrattus_CSIRO_v1

Variants

.
Variants in Gch1
325 total Variants
miRNA Target Status (No longer updated)

Predicted Target Of
Summary Value
Count of predictions:131
Count of miRNA genes:109
Interacting mature miRNAs:114
Transcripts:ENSRNOT00000014821
Prediction methods:Microtar, Miranda, Rnahybrid, Targetscan
Result types:miRGate_prediction

The detailed report is available here: Full Report CSV TAB Printer

miRNA Target Status data imported from miRGate (http://mirgate.bioinfo.cnio.es/).
For more information about miRGate, see PMID:25858286 or access the full paper here.


QTLs in Region (GRCr8)
The following QTLs overlap with this region.    Full Report CSV TAB Printer Gviewer
RGD IDSymbolNameLODP ValueTraitSub TraitChrStartStopSpecies
1641913Colcr2Colorectal carcinoma resistance QTL 26.570.0197intestine integrity trait (VT:0010554)poorly differentiated malignant colorectal tumor number (CMO:0002076)15231575947315759Rat
61424Scl1Serum cholesterol level QTL 17.70.001blood cholesterol amount (VT:0000180)serum total cholesterol level (CMO:0000363)151915576287086765Rat
10401805Kidm51Kidney mass QTL 51kidney mass (VT:0002707)both kidneys wet weight (CMO:0000085)15278592347785923Rat
5684946Bss98Bone structure and strength QTL 983.90.0026tibia strength trait (VT:1000284)tibia ultimate force (CMO:0001734)15139411584Rat
1354657Despr13Despair related QTL 130.0022locomotor behavior trait (VT:0001392)amount of experiment time spent in a discrete space in an experimental apparatus (CMO:0000958)15132342855Rat
2317750Glom26Glomerulus QTL 264.3urine protein amount (VT:0005160)urine protein level (CMO:0000591)151492659471614418Rat
1641887Alcrsp14Alcohol response QTL 14response to alcohol trait (VT:0010489)brain neurotensin receptor 1 density (CMO:0002068)15144836456Rat
631550Bw7Body weight QTL 73.6body mass (VT:0001259)body weight (CMO:0000012)152233635167336351Rat
738017Hcas7Hepatocarcinoma susceptibility QTL 72.91liver integrity trait (VT:0010547)liver nonremodeling tumorous lesion volume to total liver volume ratio (CMO:0001464)15231575953331089Rat
10755503Bp391Blood pressure QTL 3912.37arterial blood pressure trait (VT:2000000)systolic blood pressure (CMO:0000004)152272835342072050Rat
5685002Bss103Bone structure and strength QTL 1032.8tibia strength trait (VT:1000284)tibia total energy absorbed before break (CMO:0001736)151691152132439851Rat
2324620Coatc3Coat color QTL 3coat/hair pigmentation trait (VT:0010463)pigmented coat/hair area to total coat/hair area ratio (CMO:0001810)152233635152597086Rat


Expression

RNA-SEQ Expression

alimentary part of gastrointestinal system
appendage
circulatory system
ectoderm
endocrine system
endoderm
exocrine system
hemolymphoid system
hepatobiliary system
integumental system
mesenchyme
mesoderm
musculoskeletal system
nervous system
renal system
reproductive system
respiratory system
sensory system
visual system
16 12 67 163 91 90 59 92 59 6 353 192 11 142 78 91 31 17 17

Sequence


Ensembl Acc Id: ENSRNOT00000014821   ⟹   ENSRNOP00000014821
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr8 Ensembl1522,884,006 - 22,917,412 (-)Ensembl
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)Ensembl
Rnor_6.0 Ensembl1523,934,585 - 23,969,011 (-)Ensembl
Ensembl Acc Id: ENSRNOT00000106422   ⟹   ENSRNOP00000082682
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr8 Ensembl1522,884,006 - 22,917,412 (-)Ensembl
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)Ensembl
Ensembl Acc Id: ENSRNOT00000131862   ⟹   ENSRNOP00000103431
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr8 Ensembl1522,884,006 - 22,917,412 (-)Ensembl
RefSeq Acc Id: NM_024356   ⟹   NP_077332
RefSeq Status: PROVISIONAL
Type: CODING
Position:
Rat AssemblyChrPosition (strand)Source
GRCr81522,884,006 - 22,917,412 (-)NCBI
mRatBN7.21520,404,267 - 20,437,677 (-)NCBI
Rnor_6.01523,935,011 - 23,968,971 (-)NCBI
Rnor_5.01527,876,253 - 27,910,213 (-)NCBI
RGSC_v3.41523,023,996 - 23,139,794 (-)RGD
Celera1520,799,206 - 20,832,598 (-)RGD
Sequence:
Protein Sequences
Protein RefSeqs NP_077332 (Get FASTA)   NCBI Sequence Viewer  
GenBank Protein AAA41299 (Get FASTA)   NCBI Sequence Viewer  
  AAD56338 (Get FASTA)   NCBI Sequence Viewer  
  AAG30952 (Get FASTA)   NCBI Sequence Viewer  
  EDL88345 (Get FASTA)   NCBI Sequence Viewer  
Ensembl Protein ENSRNOP00000014821
  ENSRNOP00000014821.5
GenBank Protein P22288 (Get FASTA)   NCBI Sequence Viewer  
RefSeq Acc Id: NP_077332   ⟸   NM_024356
- Peptide Label: precursor
- UniProtKB: P22288 (UniProtKB/Swiss-Prot),   A6KE40 (UniProtKB/TrEMBL),   A0A8I5ZYD9 (UniProtKB/TrEMBL)
- Sequence:
Ensembl Acc Id: ENSRNOP00000014821   ⟸   ENSRNOT00000014821
Ensembl Acc Id: ENSRNOP00000082682   ⟸   ENSRNOT00000106422
Ensembl Acc Id: ENSRNOP00000103431   ⟸   ENSRNOT00000131862
Protein Domains
GTP cyclohydrolase I

Protein Structures
Name Modeler Protein Id AA Range Protein Structure
AF-P22288-F1-model_v2 AlphaFold P22288 1-241 view protein structure

Transcriptome

eQTL   View at Phenogen
WGCNA   View at Phenogen
Tissue/Strain Expression   View at Phenogen

Promoters
RGD ID:13699609
Promoter ID:EPDNEW_R10133
Type:multiple initiation site
Name:Gch1_1
Description:GTP cyclohydrolase 1
SO ACC ID:SO:0000170
Source:EPDNEW (Eukaryotic Promoter Database, http://epd.vital-it.ch/)
Experiment Methods:Single-end sequencing.
Position:
Rat AssemblyChrPosition (strand)Source
Rnor_6.01523,968,989 - 23,969,049EPDNEW

Additional Information

Database Acc Id Source(s)
AGR Gene RGD:61992 AgrOrtholog
BioCyc Gene G2FUF-14161 BioCyc
Ensembl Genes ENSRNOG00000011039 Ensembl, ENTREZGENE, UniProtKB/Swiss-Prot
Ensembl Transcript ENSRNOT00000014821 ENTREZGENE
  ENSRNOT00000014821.8 UniProtKB/Swiss-Prot
Gene3D-CATH 1.10.286.10 UniProtKB/Swiss-Prot
  3.30.1130.10 UniProtKB/Swiss-Prot
InterPro GTP-CH-I_C/QueF UniProtKB/Swiss-Prot
  GTP-CH-I_N UniProtKB/Swiss-Prot
  GTP_CycHdrlase_I UniProtKB/Swiss-Prot
  GTP_CycHdrlase_I_CS UniProtKB/Swiss-Prot
  GTP_CycHdrlase_I_dom UniProtKB/Swiss-Prot
KEGG Report rno:29244 UniProtKB/Swiss-Prot
NCBI Gene 29244 ENTREZGENE
PANTHER GTP CYCLOHYDROLASE 1 UniProtKB/Swiss-Prot
  PTHR11109 UniProtKB/Swiss-Prot
Pfam GTP_cyclohydroI UniProtKB/Swiss-Prot
PharmGKB GCH1 RGD
PhenoGen Gch1 PhenoGen
PROSITE GTP_CYCLOHYDROL_1_1 UniProtKB/Swiss-Prot
  GTP_CYCLOHYDROL_1_2 UniProtKB/Swiss-Prot
RatGTEx ENSRNOG00000011039 RatGTEx
Superfamily-SCOP Tetrahydrobiopterin biosynthesis enzymes-like UniProtKB/Swiss-Prot
UniProt A0A8I5ZYD9 ENTREZGENE, UniProtKB/TrEMBL
  A0ABK0L314_RAT UniProtKB/TrEMBL
  A6KE40 ENTREZGENE, UniProtKB/TrEMBL
  GCH1_RAT UniProtKB/Swiss-Prot, ENTREZGENE


Nomenclature History
Date Current Symbol Current Name Previous Symbol Previous Name Description Reference Status
2008-02-18 Gch1  GTP cyclohydrolase 1  Gch  GTP cyclohydrolase 1  Nomenclature updated to reflect human and mouse nomenclature 1299863 APPROVED
2002-06-10 Gch  GTP cyclohydrolase 1      Name updated 70584 APPROVED

RGD Curation Notes
Note Type Note Reference
gene_function the first and rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH(4)), an essential cofactor for tyrosine hydroxylase and nitric oxide synthase 625450
gene_function the first and rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH(4)), an essential cofactor for tyrosine hydroxylase and nitric oxide synthase 632772
gene_regulation expression and activity are upregulated by V-1 (Gcdp), a cdc10/SWI6 motif-containing protein 625450
gene_regulation induced by intrastriatal kainic acid lesion 632772