GCLC [The Human Chemical-Genetic Interaction Map Project]

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======= GCLC =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: GCLC
  * **<color #00a2e8>Official Name</color>**: glutamate-cysteine ligase catalytic subunit
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2729|2729]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P48506|P48506]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=GCLC&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20GCLC|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/606857|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate-limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]. 
  * **<color #00a2e8>UniProt Summary</color>**: N/A

<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'>
|GCS|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cellular response to L-phenylalanine derivative|
|cellular response to thyroxine stimulus|
|glutamate-cysteine ligase complex|
|negative regulation of hepatic stellate cell activation|
|glutamate-cysteine ligase activity|
|response to human chorionic gonadotropin|
|response to thyroxine|
|response to L-phenylalanine derivative|
|regulation of hepatic stellate cell activation|
|response to nitrosative stress|
|glutamate binding|
|L-ascorbic acid metabolic process|
|coenzyme binding|
|cellular response to follicle-stimulating hormone stimulus|
|cysteine metabolic process|
|glutathione biosynthetic process|
|cellular response to thyroid hormone stimulus|
|response to follicle-stimulating hormone|
|cellular response to hepatocyte growth factor stimulus|
|nonribosomal peptide biosynthetic process|
|cellular response to gonadotropin stimulus|
|response to hepatocyte growth factor|
|regulation of mitochondrial depolarization|
|response to thyroid hormone|
|response to gonadotropin|
|glutamate metabolic process|
|response to arsenic-containing substance|
|ADP binding|
|sulfur amino acid metabolic process|
|serine family amino acid metabolic process|
|regulation of membrane depolarization|
|cellular modified amino acid biosynthetic process|
|glutathione metabolic process|
|apoptotic mitochondrial changes|
|response to cadmium ion|
|response to activity|
|cellular response to amino acid stimulus|
|cellular response to glucose stimulus|
|regulation of mitochondrial membrane potential|
|glutamine family amino acid metabolic process|
|cellular response to hexose stimulus|
|cellular response to monosaccharide stimulus|
|negative regulation of protein ubiquitination|
|cell redox homeostasis|
|cellular response to mechanical stimulus|
|cellular response to carbohydrate stimulus|
|positive regulation of proteasomal ubiquitin-dependent protein catabolic process|
|negative regulation of protein modification by small protein conjugation or removal|
|water-soluble vitamin metabolic process|
|cellular glucose homeostasis|
|dicarboxylic acid metabolic process|
|positive regulation of ubiquitin-dependent protein catabolic process|
|negative regulation of extrinsic apoptotic signaling pathway|
|positive regulation of proteasomal protein catabolic process|
|cellular response to fibroblast growth factor stimulus|
|response to heat|
|response to amino acid|
|response to fibroblast growth factor|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|vitamin metabolic process|
|response to glucose|
|regulation of tube diameter|
|regulation of blood vessel diameter|
|regulation of tube size|
|positive regulation of cellular protein catabolic process|
|response to hexose|
|negative regulation of neuron apoptotic process|
|response to monosaccharide|
|regulation of ubiquitin-dependent protein catabolic process|
|regulation of extrinsic apoptotic signaling pathway|
|cellular response to insulin stimulus|
|vascular process in circulatory system|
|response to carbohydrate|
|response to temperature stimulus|
|sulfur compound biosynthetic process|
|regulation of proteasomal protein catabolic process|
|glucose homeostasis|
|carbohydrate homeostasis|
|negative regulation of cell activation|
|cellular modified amino acid metabolic process|
|response to interleukin-1|
|regulation of protein ubiquitination|
|monosaccharide metabolic process|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|cellular response to acid chemical|
|alpha-amino acid metabolic process|
|cofactor biosynthetic process|
|response to mechanical stimulus|
|response to nutrient|
|magnesium ion binding|
|positive regulation of protein catabolic process|
|regulation of proteolysis involved in cellular protein catabolic process|
|negative regulation of apoptotic signaling pathway|
|response to insulin|
|regulation of protein modification by small protein conjugation or removal|
|regulation of cellular protein catabolic process|
|coenzyme metabolic process|
|cellular response to peptide hormone stimulus|
|aging|
|response to xenobiotic stimulus|
|cellular amino acid metabolic process|
|regulation of neuron death|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|cellular response to peptide|
|cellular response to external stimulus|
|response to acid chemical|
|positive regulation of proteolysis|
|positive regulation of cellular catabolic process|
|sulfur compound metabolic process|
|response to metal ion|
|regulation of protein catabolic process|
|response to oxidative stress|
|blood circulation|
|response to peptide hormone|
|circulatory system process|
|regulation of apoptotic signaling pathway|
|cellular response to drug|
|peptide biosynthetic process|
|regulation of membrane potential|
|positive regulation of catabolic process|
|cofactor metabolic process|
|mitochondrion organization|
|response to peptide|
|carbohydrate metabolic process|
|protein heterodimerization activity|
|response to nutrient levels|
|cellular response to growth factor stimulus|
|regulation of anatomical structure size|
|amide biosynthetic process|
|peptide metabolic process|
|response to extracellular stimulus|
|response to growth factor|
|response to inorganic substance|
|cellular response to organic cyclic compound|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|regulation of cell activation|
|cellular response to nitrogen compound|
|regulation of proteolysis|
|cellular chemical homeostasis|
|cellular amide metabolic process|
|ion homeostasis|
|regulation of cellular catabolic process|
|negative regulation of apoptotic process|
|cellular homeostasis|
|negative regulation of programmed cell death|
|response to hormone|
|carboxylic acid metabolic process|
|response to organic cyclic compound|
|apoptotic process|
|negative regulation of cell death|
|regulation of catabolic process|
|response to organonitrogen compound|
|oxoacid metabolic process|
|response to drug|
|organic acid metabolic process|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|response to nitrogen compound|
|cell death|
|response to cytokine|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|organonitrogen compound biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|cellular nitrogen compound biosynthetic process|
|homeostatic process|
|regulation of cell death|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|small molecule metabolic process|
|regulation of protein modification process|
|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:exp237|NN-Diethyl-meta-toluamide 100μM R05 exp237]]|-3.64|
|[[:results:exp529|Thimerosal 0.85μM R08 exp529]]|-3.25|
|[[:results:exp356|Docosahexaenoic-acid 50μM R07 exp356]]|-3.19|
|[[:results:exp229|Dimethyloxaloylglycine 100μM R05 exp229]]|-2.91|
|[[:results:exp340|BN82002 4μM R07 exp340]]|-2.83|
|[[:results:exp129|Isonicotinamide 500μM R03 exp129]]|-2.8|
|[[:results:exp125|GSK461364A 0.005μM R03 exp125]]|-2.78|
|[[:results:exp133|MKC9989 10μM R03 exp133]]|-2.78|
|[[:results:exp143|Phenformin 20μM R03 exp143]]|-2.75|
|[[:results:exp248|UM0131023 0.05μM R05 exp248]]|-2.72|
|[[:results:exp180|Dynasore 10μM R04 exp180]]|-2.63|
|[[:results:exp230|Epigallocatechin gallate 20μM R05 exp230]]|-2.59|
|[[:results:exp264|Arsenate 40μM R06 exp264]]|-2.55|
|[[:results:exp215|Colchicine 0.009μM R05 exp215]]|-2.53|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-2.52|
|[[:results:exp113|1-Methyl-nicotinamide-chloride 1000μM R03 exp113]]|-2.49|
|[[:results:exp455|Benzoate 10000μM R08 exp455]]|-2.49|
|[[:results:exp232|Epothilone-D 0.004 to 0.006μM on day4 R05 exp232]]|-2.48|
|[[:results:exp160|Ribavirin 10 to 15μM on day4 R04 exp160]]|-2.46|
|[[:results:exp150|SGC0649 7μM R03 exp150]]|-2.46|
|[[:results:exp241|QNZ 0.01μM R05 exp241]]|-2.44|
|[[:results:exp132|Metformin 40μM R03 exp132]]|-2.43|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|-2.35|
|[[:results:exp461|BS-181 20μM R08 exp461]]|-2.34|
|[[:results:exp145|PNU96415E 10μM R03 exp145]]|-2.34|
|[[:results:exp219|A-395N 10μM R05 exp219]]|-2.32|
|[[:results:exp20|Etoposide 10μM R00 exp20]]|-2.31|
|[[:results:exp114|A-196 10μM R03 exp114]]|-2.29|
|[[:results:exp443|SNS-032 15μM R08 exp443]]|-2.29|
|[[:results:exp326|CCT251545 20μM R07 exp326]]|-2.24|
|[[:results:exp362|GSK-J4 1μM R07 exp362]]|-2.24|
|[[:results:exp392|PT-1 25μM R07 exp392]]|-2.23|
|[[:results:exp152|SGC2043 10μM R03 exp152]]|-2.23|
|[[:results:exp281|Disulfiram 4.3μM R06 exp281]]|-2.21|
|[[:results:exp175|3-Bromopyruvate 7μM R04 exp175]]|-2.18|
|[[:results:exp140|Nicotinate 1000μM R03 exp140]]|-2.18|
|[[:results:exp84|UM0125461 0.74μM R02 exp84]]|-2.16|
|[[:results:exp69|Deguelin 0.05μM R02 exp69]]|-2.15|
|[[:results:exp141|Nifurtimox 1μM R03 exp141]]|-2.14|
|[[:results:exp151|SGC0946 7μM R03 exp151]]|-2.13|
|[[:results:exp184|Ixabepilone 0.004 to 0.005μM on day4 R04 exp184]]|-2.12|
|[[:results:exp131|L-74142 5μM R03 exp131]]|-2.09|
|[[:results:exp293|Myriocin 25μM R06 exp293]]|-2.09|
|[[:results:exp245|UM0011500 5μM R05 exp245]]|-2.09|
|[[:results:exp101|Nicotinamide 1000μM R03 exp101]]|-2.07|
|[[:results:exp239|PFI-2 4μM R05 exp239]]|-2.07|
|[[:results:exp285|GW501516 25μM R06 exp285]]|-2.02|
|[[:results:exp426|FBS-Wisent 0.1 R07 exp426]]|-2.02|
|[[:results:exp262|Alda-1 10μM R06 exp262]]|-2|
|[[:results:exp449|Arsenic trioxide 60μM R08 exp449]]|-2|
|[[:results:exp128|GSK591 2.6μM R03 exp128]]|-1.99|
|[[:results:exp153|SGC2096 2.6μM R03 exp153]]|-1.99|
|[[:results:exp209|Deguelin 0.15μM R05 exp209]]|-1.98|
|[[:results:exp249|Vinorelbine 0.001μM R05 exp249]]|-1.98|
|[[:results:exp148|SB202190 10μM R03 exp148]]|-1.96|
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|-1.93|
|[[:results:exp33|Rotenone 2μM R00 exp33]]|-1.93|
|[[:results:exp275|Citral 75μM R06 exp275]]|-1.92|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-1.92|
|[[:results:exp182|IU1-47 25μM R04 exp182]]|-1.92|
|[[:results:exp103|Taxol 0.004μM R03 exp103]]|-1.92|
|[[:results:exp346|CoCl2 18μM R07 exp346]]|-1.89|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|-1.89|
|[[:results:exp298|Sucrose 20000μM R06 exp298]]|-1.86|
|[[:results:exp41|BI-2536 0.001μM R01 exp41]]|-1.85|
|[[:results:exp156|UNC2400 2μM R03 exp156]]|-1.85|
|[[:results:exp123|GSK-LSD1 10μM R03 exp123]]|-1.83|
|[[:results:exp121|Golgicide-A 2μM R03 exp121]]|-1.82|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|-1.81|
|[[:results:exp187|proTAME 5μM R04 exp187]]|-1.81|
|[[:results:exp374|Latrunculin-B 10μM R07 exp374]]|-1.8|
|[[:results:exp116|AICAR 240μM R03 exp116]]|-1.79|
|[[:results:exp149|SB203580 25μM R03 exp149]]|-1.78|
|[[:results:exp462|Cadmium 60μM R08 exp462]]|-1.77|
|[[:results:exp286|HMS-I2 1μM R06 exp286]]|-1.77|
|[[:results:exp263|Aphidicolin 0.04μM R06 exp263]]|-1.76|
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|-1.76|
|[[:results:exp170|Metformin 100 to 150μM on day4 R04 exp170]]|-1.76|
|[[:results:exp526|Sulforaphane 9μM R08 exp526 no dilution day6]]|-1.76|
|[[:results:exp115|A-366 10μM R03 exp115]]|-1.74|
|[[:results:exp300|VE-822 0.04μM R06 exp300]]|-1.74|
|[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|-1.73|
|[[:results:exp247|UM0130462 0.025 to 0.035μM day4 R05 exp247]]|-1.73|
|[[:results:exp169|BH1 1μM R04 exp169]]|-1.72|
|[[:results:exp48|Mubritinib 0.2μM R01 exp48]]|-1.72|
|[[:results:exp510|Nicotine 3000μM R08 exp510]]|-1.71|
|[[:results:exp238|Parthenolide 2.5μM R05 exp238]]|-1.71|
|[[:results:exp112|S-DABN 8μM R03 exp112]]|-1.7|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|1.81|
|[[:results:exp111|R-DABN 8μM R03 exp111]]|1.96|
|[[:results:exp407|Thapsigargin 0.005μM R07 exp407]]|2.23|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|2.32|
|[[:results:exp466|Cannabidiol 20μM R08 exp466]]|2.45|
|[[:results:exp518|RK-33 8μM R08 exp518]]|3.95|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:g:gclm|GCLM]]|0.679|
|[[:human genes:g:gss|GSS]]|0.623|
|[[:human genes:o:osgin2|OSGIN2]]|0.489|
|[[:human genes:r:rfk|RFK]]|0.455|
|[[:human genes:a:atxn10|ATXN10]]|0.452|
|[[:human genes:s:sepsecs|SEPSECS]]|0.452|
|[[:human genes:t:tbcb|TBCB]]|0.41|
|[[:human genes:c:c15orf41|C15orf41]]|0.404|
|[[:human genes:f:fh|FH]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 2/739
^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|0/16|
|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>**: 260
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.71 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='GCLC Expression in NALM6 Cells: 4.71'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>