NPC1 [The Human Chemical-Genetic Interaction Map Project]

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======= NPC1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: NPC1
  * **<color #00a2e8>Official Name</color>**: NPC intracellular cholesterol transporter 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4864|4864]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O15118|O15118]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=NPC1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NPC1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/607623|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals. {ECO:0000269|PubMed:18772377, ECO:0000269|PubMed:19563754}.

<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'>
|Sterol-sensing|
|Patched|
|MMPL|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|integral component of lysosomal membrane|
|sterol transporter activity|
|intracellular cholesterol transport|
|intracellular sterol transport|
|cellular response to low-density lipoprotein particle stimulus|
|membrane raft organization|
|cholesterol efflux|
|low-density lipoprotein particle clearance|
|response to lipoprotein particle|
|adult walking behavior|
|cellular response to lipoprotein particle stimulus|
|walking behavior|
|negative regulation of macroautophagy|
|intracellular lipid transport|
|bile acid metabolic process|
|plasma lipoprotein particle clearance|
|cholesterol binding|
|cholesterol transport|
|response to cadmium ion|
|sterol transport|
|regulation of plasma lipoprotein particle levels|
|virus receptor activity|
|adult locomotory behavior|
|cholesterol homeostasis|
|sterol homeostasis|
|negative regulation of autophagy|
|viral entry into host cell|
|entry into host cell|
|entry into host|
|lysosomal transport|
|cholesterol metabolic process|
|late endosome membrane|
|secondary alcohol metabolic process|
|lipid homeostasis|
|sterol metabolic process|
|transmembrane signaling receptor activity|
|organic hydroxy compound transport|
|vacuolar transport|
|adult behavior|
|interaction with host|
|regulation of macroautophagy|
|nuclear envelope|
|cellular response to steroid hormone stimulus|
|locomotory behavior|
|viral life cycle|
|signaling receptor activity|
|membrane raft|
|lysosome|
|negative regulation of cellular catabolic process|
|macromolecule glycosylation|
|protein glycosylation|
|steroid metabolic process|
|process utilizing autophagic mechanism|
|autophagy|
|establishment of protein localization to membrane|
|glycosylation|
|lipid transport|
|lysosomal membrane|
|negative regulation of catabolic process|
|alcohol metabolic process|
|lipid localization|
|glycoprotein biosynthetic process|
|response to steroid hormone|
|regulation of autophagy|
|response to metal ion|
|glycoprotein metabolic process|
|organic hydroxy compound metabolic process|
|protein localization to membrane|
|cellular response to lipid|
|monocarboxylic acid metabolic process|
|response to inorganic substance|
|cellular response to organic cyclic compound|
|endocytosis|
|behavior|
|cellular response to hormone stimulus|
|carbohydrate derivative biosynthetic process|
|import into cell|
|perinuclear region of cytoplasm|
|viral process|
|symbiotic process|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|response to lipid|
|membrane organization|
|response to hormone|
|carboxylic acid metabolic process|
|response to organic cyclic compound|
|Golgi apparatus|
|regulation of catabolic process|
|negative regulation of cell death|
|response to organonitrogen compound|
|oxoacid metabolic process|
|endoplasmic reticulum|
|response to drug|
|organic acid metabolic process|
|carbohydrate derivative metabolic process|
|response to nitrogen compound|
|chemical homeostasis|
|lipid metabolic process|
|cellular response to endogenous stimulus|
|integral component of plasma membrane|
|organonitrogen compound biosynthetic process|
|response to endogenous stimulus|
|intracellular transport|
|cellular protein localization|
|cellular macromolecule localization|
|establishment of protein localization|
|homeostatic process|
|regulation of cell death|
|cellular macromolecule biosynthetic process|
|small molecule metabolic process|
|macromolecule biosynthetic process|
|cellular catabolic process|
|establishment of localization in cell|
|extracellular region|
|vesicle-mediated transport|
|membrane|
</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:exp169|BH1 1μM R04 exp169]]|-2.62|
|[[:results:exp454|Bafilomycin-A1 0.009μM R08 exp454]]|-2.42|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|-2.06|
|[[:results:exp52|Ribavirin 10μM R01 exp52]]|-2.05|
|[[:results:exp510|Nicotine 3000μM R08 exp510]]|-1.98|
|[[:results:exp321|ABT-702 5μM plus Deferoxamine 11μM R07 exp321]]|-1.97|
|[[:results:exp483|FTY720 3μM R08 exp483]]|-1.96|
|[[:results:exp345|Cidofovir 10μM R07 exp345]]|-1.83|
|[[:results:exp508|NN-Dimethylsphingosine 2.5μM R08 exp508]]|-1.8|
|[[:results:exp475|CyclicAMP 200μM R08 exp475]]|-1.73|
|[[:results:exp346|CoCl2 18μM R07 exp346]]|-1.73|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|1.72|
|[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|1.75|
|[[:results:exp222|Betulinic acid 10 to 15μM on day4 R05 exp222]]|1.78|
|[[:results:exp175|3-Bromopyruvate 7μM R04 exp175]]|1.85|
|[[:results:exp450|Artemisinin 50μM R08 exp450]]|1.96|
|[[:results:exp245|UM0011500 5μM R05 exp245]]|2.51|
|[[:results:exp506|Momordin-Ic 10μM R08 exp506]]|3.76|
|[[:results:exp246|UM0011500 10μM R05 exp246]]|5.97|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.508|
|[[:human genes:n:npc2|NPC2]]|0.447|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^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>**: 2402
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.62 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='NPC1 Expression in NALM6 Cells: 6.62'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>