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Browse GCH1

Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus
Domain PF01227 GTP cyclohydrolase I
Function

Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.

> Gene Ontology
 
Biological Process GO:0000302 response to reactive oxygen species
GO:0000303 response to superoxide
GO:0000305 response to oxygen radical
GO:0002237 response to molecule of bacterial origin
GO:0003013 circulatory system process
GO:0003018 vascular process in circulatory system
GO:0006575 cellular modified amino acid metabolic process
GO:0006584 catecholamine metabolic process
GO:0006729 tetrahydrobiopterin biosynthetic process
GO:0006732 coenzyme metabolic process
GO:0006760 folic acid-containing compound metabolic process
GO:0006801 superoxide metabolic process
GO:0006809 nitric oxide biosynthetic process
GO:0006979 response to oxidative stress
GO:0008015 blood circulation
GO:0008217 regulation of blood pressure
GO:0009108 coenzyme biosynthetic process
GO:0009396 folic acid-containing compound biosynthetic process
GO:0009636 response to toxic substance
GO:0009712 catechol-containing compound metabolic process
GO:0009713 catechol-containing compound biosynthetic process
GO:0010035 response to inorganic substance
GO:0014916 regulation of lung blood pressure
GO:0018958 phenol-containing compound metabolic process
GO:0019430 removal of superoxide radicals
GO:0032496 response to lipopolysaccharide
GO:0032768 regulation of monooxygenase activity
GO:0032770 positive regulation of monooxygenase activity
GO:0033555 multicellular organismal response to stress
GO:0034341 response to interferon-gamma
GO:0034599 cellular response to oxidative stress
GO:0034612 response to tumor necrosis factor
GO:0034614 cellular response to reactive oxygen species
GO:0035150 regulation of tube size
GO:0035998 7,8-dihydroneopterin 3'-triphosphate biosynthetic process
GO:0042311 vasodilation
GO:0042398 cellular modified amino acid biosynthetic process
GO:0042416 dopamine biosynthetic process
GO:0042417 dopamine metabolic process
GO:0042423 catecholamine biosynthetic process
GO:0042558 pteridine-containing compound metabolic process
GO:0042559 pteridine-containing compound biosynthetic process
GO:0045776 negative regulation of blood pressure
GO:0046146 tetrahydrobiopterin metabolic process
GO:0046189 phenol-containing compound biosynthetic process
GO:0046209 nitric oxide metabolic process
GO:0046653 tetrahydrofolate metabolic process
GO:0046654 tetrahydrofolate biosynthetic process
GO:0048265 response to pain
GO:0050880 regulation of blood vessel size
GO:0050884 neuromuscular process controlling posture
GO:0050905 neuromuscular process
GO:0050999 regulation of nitric-oxide synthase activity
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:0051066 dihydrobiopterin metabolic process
GO:0051186 cofactor metabolic process
GO:0051188 cofactor biosynthetic process
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051291 protein heterooligomerization
GO:0051341 regulation of oxidoreductase activity
GO:0051353 positive regulation of oxidoreductase activity
GO:0071450 cellular response to oxygen radical
GO:0071451 cellular response to superoxide
GO:0072593 reactive oxygen species metabolic process
GO:0090066 regulation of anatomical structure size
GO:0090322 regulation of superoxide metabolic process
GO:0098754 detoxification
GO:0098869 cellular oxidant detoxification
GO:1900407 regulation of cellular response to oxidative stress
GO:1901031 regulation of response to reactive oxygen species
GO:1901615 organic hydroxy compound metabolic process
GO:1901617 organic hydroxy compound biosynthetic process
GO:1902882 regulation of response to oxidative stress
GO:1903409 reactive oxygen species biosynthetic process
GO:1990748 cellular detoxification
GO:2000121 regulation of removal of superoxide radicals
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2001057 reactive nitrogen species metabolic process
Molecular Function GO:0003933 GTP cyclohydrolase activity
GO:0003934 GTP cyclohydrolase I activity
GO:0005525 GTP binding
GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
GO:0016814 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines
GO:0019001 guanyl nucleotide binding
GO:0019238 cyclohydrolase activity
GO:0030742 GTP-dependent protein binding
GO:0031369 translation initiation factor binding
GO:0032561 guanyl ribonucleotide binding
GO:0048037 cofactor binding
GO:0050662 coenzyme binding
Cellular Component GO:0005635 nuclear envelope
GO:0031965 nuclear membrane
> KEGG and Reactome Pathway
 
KEGG hsa00790 Folate biosynthesis
hsa01100 Metabolic pathways
Reactome R-HSA-1430728: Metabolism
R-HSA-202131: Metabolism of nitric oxide
R-HSA-1474151: Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-203765: eNOS activation and regulation
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between GCH1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between GCH1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
22753274Colon CarcinomaInhibit immunityWe found that inhibition or silencing of GCH1 reduced tumor cell proliferation and survival and the tube formation of human umbilical vein endothelial cells, which upon hypoxia increased GCH1 and endothelial NOS expression, the latter prevented by inhibition of GCH1. The treatment with the GCH1 inhibitor shifted the phenotype of tumor associated macrophages from the proangiogenic M2 towards M1, accompanied with a shift of plasma chemokine profiles towards tumor-attacking chemokines including CXCL10 and RANTES. GCH1 expression was increased in mouse AOM/DSS-induced colon tumors and in high grade human colon and skin cancer and oppositely, the growth of GCH1-deficient HT29-Luc tumor cells in mice was strongly reduced. The data suggest that GCH1 inhibition reduces tumor growth by (i) direct killing of tumor cells, (ii) by inhibiting angiogenesis, and (iii) by enhancing the antitumoral immune response.
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of GCH1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of GCH1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.4480.284
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4960.717
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.420.659
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5740.169
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0920.945
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.4250.438
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4510.282
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.7370.514
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1270.92
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3020.711
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3620.78
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0260.79
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of GCH1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GCH1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GCH1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GCH1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GCH1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of GCH1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between GCH1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolGCH1
NameGTP cyclohydrolase 1
Aliases GTPCH1; DYT5a; dopa-responsive dystonia; GCH; DYT5; GTP-CH-1; HPABH4B; GTP-CH-I; guanosine 5'-triphosphate c ......
Chromosomal Location14q22.1-q22.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting GCH1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting GCH1.
ID Name Drug Type Targets #Targets
DB02325Isopropyl AlcoholSmall MoleculeACP5, ADI1, AHCY, CHIT1, DCXR, DDX39B, GCH1, GDF5, GM2A, PLA2G2A, ......15
DB02377GuanineSmall MoleculeGCH1, PNP2