NPC1L1

Gene Information

Official Symbol: NPC1L1
Official Name: NPC1 like intracellular cholesterol transporter 1
Aliases and Previous Symbols: N/A
Entrez ID: 29881
UniProt: Q9UHC9
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009].
UniProt Summary: Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption. Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. Acts as a negative regulator of NPC2 and down- regulates its expression and secretion by inhibiting its maturation and accelerating its degradation. {ECO:0000269|PubMed:15928087, ECO:0000269|PubMed:22095670}.

Pfam Domains GO Terms

CRISPR Data

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

Screen	Score
BI-2536 0.02μM R03 exp96	-1.86
proTAME 5μM R04 exp187	1.72
Rotenone 2μM R00 exp33	1.84
Vinblastine 0.015μM R05 exp208	2.02
DABN racemic mixture R03 exp93	2.16
SB743921 0.001μM R05 exp244	2.48

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

Essentiality in NALM6

Essentiality Rank: 3179
Expression level (log2 read counts): -2.21

Expression Distribution

Gene	Correlation
HGC6.3	0.454
RRM1	0.436

Sterol-sensing
Patched

spanning component of plasma membrane
cellular response to sterol depletion
intestinal cholesterol absorption
response to sterol depletion
intestinal lipid absorption
lipid digestion
myosin V binding
intestinal absorption
cholesterol biosynthetic process
secondary alcohol biosynthetic process
sterol biosynthetic process
brush border membrane
cholesterol transport
drug binding
sterol transport
digestive system process
alcohol biosynthetic process
digestion
cholesterol metabolic process
lipoprotein metabolic process
steroid biosynthetic process
secondary alcohol metabolic process
sterol metabolic process
organic hydroxy compound transport
cytoplasmic vesicle membrane
Rab GTPase binding
organic hydroxy compound biosynthetic process
steroid metabolic process
lipid transport
alcohol metabolic process
apical plasma membrane
lipid localization
organic hydroxy compound metabolic process
lipid biosynthetic process
small molecule biosynthetic process
response to drug
lipid metabolic process
organic cyclic compound biosynthetic process
cellular response to stress
small molecule metabolic process