GCH1

Entrez Summary: 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].
UniProt Summary: 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. {ECO:0000269|PubMed:12176133, ECO:0000269|PubMed:16338639, ECO:0000269|PubMed:17057711, ECO:0000269|PubMed:8068008, ECO:0000269|PubMed:9445252}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Tubacin 1.6μM R07 exp416	-2.54
Epigallocatechin gallate 20μM R05 exp230	-2.04
Thimerosal 0.85μM R08 exp529	-1.96
THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412	-1.96
Docosahexaenoic-acid 50μM R07 exp356	-1.87
Resveratrol 16μM R03 exp147	-1.78
Etoposide 0.1μM R05 exp198	1.72
Fluvastatin 2.2μM R06 exp282	1.87
Hypoxia 5%O2 R04 exp191	1.9
CCT251545 20μM R07 exp326	1.95
Senexin-A 25μM R07 exp400	2.03
Cerivastatin 0.15μM R05 exp226	2.14
Demecolcine 0.03μM R05 exp228	2.34

Global Fraction of Cell Lines Where Essential: 1/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	1/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Expression Distribution

7,8-dihydroneopterin 3-triphosphate biosynthetic process
GTP cyclohydrolase I activity
dihydrobiopterin metabolic process
regulation of lung blood pressure
tetrahydrobiopterin biosynthetic process
tetrahydrofolate biosynthetic process
tetrahydrobiopterin metabolic process
regulation of removal of superoxide radicals
dopamine biosynthetic process
folic acid-containing compound biosynthetic process
coenzyme binding
nitric oxide biosynthetic process
pteridine-containing compound biosynthetic process
nitric oxide metabolic process
neuromuscular process controlling posture
diol biosynthetic process
tetrahydrofolate metabolic process
catecholamine biosynthetic process
catechol-containing compound biosynthetic process
reactive nitrogen species metabolic process
neuron projection terminus
positive regulation of nitric-oxide synthase activity
diol metabolic process
mitogen-activated protein kinase binding
translation initiation factor binding
GTP-dependent protein binding
positive regulation of heart rate
reactive oxygen species biosynthetic process
positive regulation of monooxygenase activity
dopamine metabolic process
folic acid-containing compound metabolic process
response to pain
vasodilation
regulation of superoxide metabolic process
phenol-containing compound biosynthetic process
regulation of response to reactive oxygen species
pteridine-containing compound metabolic process
positive regulation of heart contraction
neurotransmitter biosynthetic process
catechol-containing compound metabolic process