======= GCH1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: GCH1
  * **<color #00a2e8>Official Name</color>**: GTP cyclohydrolase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2643|2643]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P30793|P30793]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=GCH1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20GCH1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600225|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|GTP cyclohydroI|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|catecholamine metabolic process|
|regulation of nitric-oxide synthase activity|
|negative regulation of blood pressure|
|cellular modified amino acid biosynthetic process|
|positive regulation of oxidoreductase activity|
|regulation of monooxygenase activity|
|positive regulation of blood vessel diameter|
|polyol biosynthetic process|
|multicellular organismal response to stress|
|positive regulation of blood circulation|
|regulation of cellular response to oxidative stress|
|phenol-containing compound metabolic process|
|regulation of response to oxidative stress|
|neurotransmitter metabolic process|
|regulation of oxidoreductase activity|
|regulation of heart rate|
|protein heterooligomerization|
|neuromuscular process|
|polyol metabolic process|
|reactive oxygen species metabolic process|
|alcohol biosynthetic process|
|coenzyme biosynthetic process|
|regulation of blood vessel diameter|
|regulation of tube diameter|
|regulation of tube size|
|vascular process in circulatory system|
|regulation of reactive oxygen species metabolic process|
|response to interferon-gamma|
|regulation of blood pressure|
|organic hydroxy compound biosynthetic process|
|ammonium ion metabolic process|
|cellular modified amino acid metabolic process|
|cofactor biosynthetic process|
|nuclear membrane|
|regulation of heart contraction|
|coenzyme metabolic process|
|cytoplasmic vesicle|
|response to tumor necrosis factor|
|regulation of blood circulation|
|carboxylic acid biosynthetic process|
|organic acid biosynthetic process|
|response to lipopolysaccharide|
|alcohol metabolic process|
|response to molecule of bacterial origin|
|GTPase activity|
|protein homooligomerization|
|regulation of neurotransmitter levels|
|GTP binding|
|blood circulation|
|circulatory system process|
|cofactor metabolic process|
|organic hydroxy compound metabolic process|
|drug metabolic process|
|regulation of anatomical structure size|
|protein complex oligomerization|
|amide biosynthetic process|
|organophosphate biosynthetic process|
|small molecule biosynthetic process|
|regulation of system process|
|protein-containing complex|
|response to bacterium|
|calcium ion binding|
|regulation of cellular response to stress|
|innate immune response|
|cellular amide metabolic process|
|zinc ion binding|
|response to lipid|
|protein homodimerization activity|
|organophosphate metabolic process|
|carboxylic acid metabolic process|
|defense response to other organism|
|oxoacid metabolic process|
|organic acid metabolic process|
|response to cytokine|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|nervous system process|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|regulation of response to stress|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|cellular nitrogen compound biosynthetic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|positive regulation of molecular function|
|protein-containing complex subunit organization|
|immune response|
|system process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-2.54|
|[[:results:exp230|Epigallocatechin gallate 20μM R05 exp230]]|-2.04|
|[[:results:exp529|Thimerosal 0.85μM R08 exp529]]|-1.96|
|[[:results:exp412|THZ531 0.11 to 0.125 to 0.35μM on day4 then day6 R07 exp412]]|-1.96|
|[[:results:exp356|Docosahexaenoic-acid 50μM R07 exp356]]|-1.87|
|[[:results:exp147|Resveratrol 16μM R03 exp147]]|-1.78|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|1.72|
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|1.87|
|[[:results:exp191|Hypoxia 5%O2 R04 exp191]]|1.9|
|[[:results:exp326|CCT251545 20μM R07 exp326]]|1.95|
|[[:results:exp400|Senexin-A 25μM R07 exp400]]|2.03|
|[[:results:exp226|Cerivastatin 0.15μM R05 exp226]]|2.14|
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|2.34|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:pts|PTS]]|0.624|
|[[:human genes:h:hgc6.3|HGC6.3]]|0.485|
|[[:human genes:t:tgfbrap1|TGFBRAP1]]|0.433|
|[[:human genes:p:psenen|PSENEN]]|0.403|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 933
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.95 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='GCH1 Expression in NALM6 Cells: 4.95'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>