Gch1 (GTP cyclohydrolase 1) - Rat Genome Database

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Gene: Gch1 (GTP cyclohydrolase 1) Rattus norvegicus
Symbol: Gch1
Name: GTP cyclohydrolase 1
RGD ID: 61992
Description: Enables several functions, including GTP cyclohydrolase I activity; GTP-dependent protein binding activity; and 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 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
Previously known as: Gch; GTP cyclohydrase I; GTP cyclohydrolase I; GTP-CH-I; GTPCH; GTPCH-1
RGD Orthologs
Green Monkey
Naked Mole-Rat
Alliance Genes
More Info more info ...
Latest Assembly: mRatBN7.2 - mRatBN7.2 Assembly
Rat AssemblyChrPosition (strand)SourceGenome Browsers
mRatBN7.21520,404,267 - 20,437,727 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)EnsemblmRatBN7.2 Ensembl
UTH_Rnor_SHR_Utx1523,184,907 - 23,218,319 (-)NCBIRnor_SHRUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01524,142,871 - 24,176,283 (-)NCBIRnor_SHRSPUTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01522,394,011 - 22,427,378 (-)NCBIRnor_WKYUTH_Rnor_WKY_Bbb_1.0
Rnor_6.01523,935,011 - 23,968,971 (-)NCBIRnor6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1523,934,585 - 23,969,011 (-)EnsemblRnor6.0rn6Rnor6.0
Rnor_5.01527,876,253 - 27,910,213 (-)NCBIRnor5.0Rnor_5.0rn5Rnor5.0
RGSC_v3.41523,023,996 - 23,139,794 (-)NCBIRGSC3.4RGSC_v3.4rn4RGSC3.4
RGSC_v3.11523,039,695 - 23,155,494 (-)NCBI
Celera1520,799,206 - 20,832,598 (-)NCBICelera
Cytogenetic Map15p14NCBI
JBrowse: View Region in Genome Browser (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)
adenine  (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[b]fluoranthene  (ISO)
bisphenol A  (EXP,ISO)
bisphenol F  (ISO)
butanal  (ISO)
cadmium dichloride  (EXP)
Calcimycin  (EXP)
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)
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)
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)
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)
zinc atom  (ISO)
zinc(0)  (ISO)

Gene Ontology Annotations     Click to see Annotation Detail View

Cellular Component
cytoplasm  (IBA,IEA,ISO)
cytoplasmic vesicle  (ISO)
cytosol  (ISO)
mitochondrion  (IDA)
nuclear membrane  (IEA,ISO)
nucleoplasm  (IEA,ISO)
nucleus  (IDA,IEA,ISO)
protein-containing complex  (IDA,ISO)

Molecular Function

Molecular Pathway Annotations     Click to see Annotation Detail View

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  


Comparative Map Data
(Rattus norvegicus - Norway rat)
Rat AssemblyChrPosition (strand)SourceGenome Browsers
mRatBN7.21520,404,267 - 20,437,727 (-)NCBImRatBN7.2mRatBN7.2
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)EnsemblmRatBN7.2 Ensembl
UTH_Rnor_SHR_Utx1523,184,907 - 23,218,319 (-)NCBIRnor_SHRUTH_Rnor_SHR_Utx
UTH_Rnor_SHRSP_BbbUtx_1.01524,142,871 - 24,176,283 (-)NCBIRnor_SHRSPUTH_Rnor_SHRSP_BbbUtx_1.0
UTH_Rnor_WKY_Bbb_1.01522,394,011 - 22,427,378 (-)NCBIRnor_WKYUTH_Rnor_WKY_Bbb_1.0
Rnor_6.01523,935,011 - 23,968,971 (-)NCBIRnor6.0Rnor_6.0rn6Rnor6.0
Rnor_6.0 Ensembl1523,934,585 - 23,969,011 (-)EnsemblRnor6.0rn6Rnor6.0
Rnor_5.01527,876,253 - 27,910,213 (-)NCBIRnor5.0Rnor_5.0rn5Rnor5.0
RGSC_v3.41523,023,996 - 23,139,794 (-)NCBIRGSC3.4RGSC_v3.4rn4RGSC3.4
RGSC_v3.11523,039,695 - 23,155,494 (-)NCBI
Celera1520,799,206 - 20,832,598 (-)NCBICelera
Cytogenetic Map15p14NCBI
(Homo sapiens - human)
Human AssemblyChrPosition (strand)SourceGenome Browsers
GRCh381454,842,017 - 54,902,826 (-)NCBIGRCh38GRCh38hg38GRCh38
GRCh38.p14 Ensembl1454,842,008 - 54,902,826 (-)EnsemblGRCh38hg38GRCh38
GRCh371455,308,735 - 55,369,544 (-)NCBIGRCh37GRCh37hg19GRCh37
Build 361454,378,473 - 54,439,292 (-)NCBINCBI36Build 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
(Mus musculus - house mouse)
Mouse AssemblyChrPosition (strand)SourceGenome Browsers
GRCm391447,391,352 - 47,426,870 (-)NCBIGRCm39GRCm39mm39
GRCm39 Ensembl1447,391,352 - 47,426,870 (-)EnsemblGRCm39 Ensembl
GRCm381447,153,895 - 47,189,413 (-)NCBIGRCm38GRCm38mm10GRCm38
GRCm38.p6 Ensembl1447,153,895 - 47,189,413 (-)EnsemblGRCm38mm10GRCm38
MGSCv371447,773,570 - 47,809,077 (-)NCBIGRCm37MGSCv37mm9NCBIm37
MGSCv361446,075,772 - 46,111,279 (-)NCBIMGSCv36mm8
Celera1443,334,771 - 43,370,387 (-)NCBICelera
Cytogenetic Map14C1NCBI
cM Map1424.6NCBI
(Chinchilla lanigera - long-tailed chinchilla)
Chinchilla AssemblyChrPosition (strand)SourceGenome Browsers
ChiLan1.0 EnsemblNW_0049554098,624,468 - 8,668,614 (+)EnsemblChiLan1.0
ChiLan1.0NW_0049554098,624,225 - 8,670,436 (+)NCBIChiLan1.0ChiLan1.0
(Pan paniscus - bonobo/pygmy chimpanzee)
Bonobo AssemblyChrPosition (strand)SourceGenome Browsers
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 (-)Ensemblpanpan1.1panPan2
(Canis lupus familiaris - dog)
Dog AssemblyChrPosition (strand)SourceGenome Browsers
CanFam3.1830,733,422 - 30,784,067 (-)NCBICanFam3.1CanFam3.1canFam3CanFam3.1
CanFam3.1 Ensembl830,732,608 - 30,784,156 (-)EnsemblCanFam3.1canFam3CanFam3.1
Dog10K_Boxer_Tasha830,501,844 - 30,552,428 (-)NCBIDog10K_Boxer_Tasha
ROS_Cfam_1.0830,989,520 - 31,040,202 (-)NCBIROS_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_1.0
(Ictidomys tridecemlineatus - thirteen-lined ground squirrel)
Squirrel AssemblyChrPosition (strand)SourceGenome Browsers
HiC_Itri_2NW_02440864074,457,811 - 74,501,265 (+)NCBIHiC_Itri_2
SpeTri2.0NW_004936697232,048 - 275,420 (+)NCBISpeTri2.0SpeTri2.0SpeTri2.0
(Sus scrofa - pig)
Pig AssemblyChrPosition (strand)SourceGenome Browsers
Sscrofa11.1 Ensembl1184,199,679 - 184,257,315 (-)EnsemblSscrofa11.1susScr11Sscrofa11.1
Sscrofa11.11184,201,232 - 184,264,060 (-)NCBISscrofa11.1Sscrofa11.1susScr11Sscrofa11.1
Sscrofa10.21204,648,349 - 204,712,905 (-)NCBISscrofa10.2Sscrofa10.2susScr3
(Chlorocebus sabaeus - green monkey)
Green Monkey AssemblyChrPosition (strand)SourceGenome Browsers
ChlSab1.12432,029,997 - 32,079,656 (-)NCBIChlSab1.1ChlSab1.1chlSab2
ChlSab1.1 Ensembl2432,027,648 - 32,079,490 (-)EnsemblChlSab1.1ChlSab1.1 EnsemblchlSab2
Vero_WHO_p1.0NW_02366605320,264,246 - 20,316,487 (-)NCBIVero_WHO_p1.0Vero_WHO_p1.0
(Heterocephalus glaber - naked mole-rat)
Naked Mole-Rat AssemblyChrPosition (strand)SourceGenome Browsers
HetGla_female_1.0 EnsemblNW_00462473114,459,303 - 14,500,429 (+)EnsemblHetGla_female_1.0HetGla_female_1.0 EnsemblhetGla2
HetGla 1.0NW_00462473114,459,164 - 14,502,485 (+)NCBIHetGla_female_1.0HetGla 1.0hetGla2


Variants in Gch1
423 total Variants
miRNA Target Status

Predicted Target Of
Summary Value
Count of predictions:131
Count of miRNA genes:109
Interacting mature miRNAs:114
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 (mRatBN7.2)
The following QTLs overlap with this region.    Full Report CSV TAB Printer Gviewer
RGD IDSymbolNameLODP ValueTraitSub TraitChrStartStopSpecies
1354657Despr13Despair related QTL 130.0022locomotor behavior trait (VT:0001392)amount of experiment time spent in a discrete space in an experimental apparatus (CMO:0000958)15129912054Rat
8552920Pigfal8Plasma insulin-like growth factor 1 level QTL 83blood insulin-like growth factor amount (VT:0010479)plasma insulin-like growth factor 1 level (CMO:0001299)15134723002Rat
8694361Abfw6Abdominal fat weight QTL 610.20.001visceral adipose mass (VT:0010063)abdominal fat pad weight to body weight ratio (CMO:0000095)15134723002Rat
9589149Insul29Insulin level QTL 299.060.001blood insulin amount (VT:0001560)plasma insulin level (CMO:0000342)15134723002Rat
731170Pur3Proteinuria QTL 32.30.0005urine protein amount (VT:0005160)urine protein excretion rate (CMO:0000759)15141686771Rat
1641887Alcrsp14Alcohol response QTL 14response to alcohol trait (VT:0010489)brain neurotensin receptor 1 density (CMO:0002068)15142356671Rat
2298549Neuinf12Neuroinflammation QTL 123.5nervous system integrity trait (VT:0010566)spinal cord beta-2 microglobulin mRNA level (CMO:0002125)15155302115Rat
10401805Kidm51Kidney mass QTL 51kidney mass (VT:0002707)both kidneys wet weight (CMO:0000085)1530632945306329Rat
1641913Colcr2Colorectal carcinoma resistance QTL 26.570.0197intestine integrity trait (VT:0010554)colorectal tumor number (CMO:0001794)15226636822711984Rat
1641913Colcr2Colorectal carcinoma resistance QTL 26.570.0197intestine integrity trait (VT:0010554)poorly differentiated malignant colorectal tumor number (CMO:0002076)15226636822711984Rat
738017Hcas7Hepatocarcinoma susceptibility QTL 72.91liver integrity trait (VT:0010547)liver nonremodeling tumorous lesion volume to total liver volume ratio (CMO:0001464)15226636846921453Rat
1582251Gluco24Glucose level QTL 243.20.0008blood glucose amount (VT:0000188)blood glucose level (CMO:0000046)15553075650530756Rat
631273Lecl2Lens clarity QTL 20.001lens clarity trait (VT:0001304)age of onset/diagnosis of cataract (CMO:0001584)151059608955596089Rat
2300167Bmd63Bone mineral density QTL 635.90.0001femur mineral mass (VT:0010011)volumetric bone mineral density (CMO:0001553)151111114256111142Rat
2300173Bmd62Bone mineral density QTL 6212.80.0001lumbar vertebra mineral mass (VT:0010511)volumetric bone mineral density (CMO:0001553)151111114256111142Rat
2293688Bss29Bone structure and strength QTL 295.310.0001femur morphology trait (VT:0000559)femur midshaft cortical cross-sectional area (CMO:0001663)151111114256111142Rat
2317750Glom26Glomerulus QTL 264.3urine protein amount (VT:0005160)urine protein level (CMO:0000591)151249614165205939Rat
5685002Bss103Bone structure and strength QTL 1032.8tibia strength trait (VT:1000284)tibia total energy absorbed before break (CMO:0001736)151448116528469888Rat
61424Scl1Serum cholesterol level QTL 17.70.001blood cholesterol amount (VT:0000180)serum total cholesterol level (CMO:0000363)151672552880672115Rat
1331729Rf42Renal function QTL 423.071kidney blood vessel physiology trait (VT:0100012)absolute change in renal blood flow rate (CMO:0001168)151736289773690657Rat
631550Bw7Body weight QTL 73.6body mass (VT:0001259)body weight (CMO:0000012)151985656634924750Rat
2324620Coatc3Coat color QTL 3coat/hair pigmentation trait (VT:0010463)pigmented coat/hair area to total coat/hair area ratio (CMO:0001810)151985656646187442Rat


RNA-SEQ Expression
High: > 1000 TPM value   Medium: Between 11 and 1000 TPM
Low: Between 0.5 and 10 TPM   Below Cutoff: < 0.5 TPM

alimentary part of gastrointestinal system circulatory system endocrine system exocrine system hemolymphoid system hepatobiliary system integumental system musculoskeletal system nervous system renal system reproductive system respiratory system appendage
Medium 2 43 35 11 35 2 3 8
Low 1 43 14 6 8 6 7 8 72 35 31 3 7
Below cutoff 1 3 6 1


RefSeq Acc Id: ENSRNOT00000014821   ⟹   ENSRNOP00000014821
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)Ensembl
Rnor_6.0 Ensembl1523,934,585 - 23,969,011 (-)Ensembl
RefSeq Acc Id: ENSRNOT00000106422   ⟹   ENSRNOP00000082682
Rat AssemblyChrPosition (strand)Source
mRatBN7.2 Ensembl1520,402,527 - 20,437,698 (-)Ensembl
RefSeq Acc Id: NM_024356   ⟹   NP_077332
Rat AssemblyChrPosition (strand)Source
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
RefSeq Acc Id: XM_039093210   ⟹   XP_038949138
Rat AssemblyChrPosition (strand)Source
mRatBN7.21520,407,425 - 20,437,727 (-)NCBI
RefSeq Acc Id: NP_077332   ⟸   NM_024356
- Peptide Label: precursor
- UniProtKB: P22288 (UniProtKB/Swiss-Prot),   A6KE40 (UniProtKB/TrEMBL),   A0A8I5ZYD9 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: ENSRNOP00000014821   ⟸   ENSRNOT00000014821
RefSeq Acc Id: XP_038949138   ⟸   XM_039093210
- Peptide Label: isoform X1
RefSeq Acc Id: ENSRNOP00000082682   ⟸   ENSRNOT00000106422
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


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

RGD ID:13699609
Promoter ID:EPDNEW_R10133
Type:multiple initiation site
Description:GTP cyclohydrolase 1
SO ACC ID:SO:0000170
Source:EPDNEW (Eukaryotic Promoter Database, http://epd.vital-it.ch/)
Experiment Methods:Single-end sequencing.
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, UniProtKB/TrEMBL
  ENSRNOG00055027391 UniProtKB/Swiss-Prot
  ENSRNOG00060023866 UniProtKB/Swiss-Prot
  ENSRNOG00065033111 UniProtKB/Swiss-Prot
Ensembl Transcript ENSRNOT00000014821 ENTREZGENE
  ENSRNOT00000014821.8 UniProtKB/Swiss-Prot
  ENSRNOT00000106422.1 UniProtKB/TrEMBL
  ENSRNOT00055047412 UniProtKB/Swiss-Prot
  ENSRNOT00060041347 UniProtKB/Swiss-Prot
  ENSRNOT00065056961 UniProtKB/Swiss-Prot
Gene3D-CATH UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  3.30.1130.10 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
InterPro GTP-CH-I_C/QueF UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  GTP-CH-I_N UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  GTP_CycHdrlase_I UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  GTP_CycHdrlase_I_CS UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  GTP_CycHdrlase_I_dom UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
KEGG Report rno:29244 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  PTHR11109 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
Pfam GTP_cyclohydroI UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
PhenoGen Gch1 PhenoGen
  GTP_CYCLOHYDROL_1_2 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
RatGTEx ENSRNOG00000011039 RatGTEx
  ENSRNOG00055027391 RatGTEx
  ENSRNOG00060023866 RatGTEx
  ENSRNOG00065033111 RatGTEx
Superfamily-SCOP Tetrahydrobiopterin biosynthesis enzymes-like UniProtKB/Swiss-Prot, UniProtKB/TrEMBL

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