Property Summary

NCBI Gene PubMed Count 76
PubMed Score 208.60
PubTator Score 163.34

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (6)

 OMIM Phenotype (1)

Gene RIF (75)

PMID Text
26800364 Study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.
26492642 The frequencies of NPC1L1 polymorphisms in Chinese Hans are comparable to Japanese population but totally different from Caucasians, African-Americans and Hispanic individuals
26253792 No significant association between investigated NPC1L1 variants and risk of coronary atherosclerosis could be observed.
25841872 Results show that genetic variation in NPC1L1 is associated with a reduction in risk of IVD, with a corresponding reduction in LDL cholesterol, but with a concomitant increased risk of gallstone disease
25770315 The effect of lower LDL-C on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both is approximately the same per unit lower LDL-C and log-linearly proportional to the absolute exposure to lower LDL-C.
25739390 To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells.
25696002 demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In
25589339 Lipid-lowering response to ezetimibe is not impacted by the NPC1L1 polymorphisms studied in Chilean hypercholesterolemic subjects.
25463095 NPC1L1-mediated cholesterol absorption is a major determinant of blood levels of apolipoprotein B-containing atherogenic lipoproteins
25390462 Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease.
25331956 Numb specifically regulates NPC1L1-mediated cholesterol absorption both in human intestine and liver, distinct from ARH and Dab2, which selectively participate in LDLR-mediated LDL uptake.
25056759 NPC1L1 polymorphism is associated with sitosterolaemia.
24974575 NPC1L1-133A > G SNP influences the ApoA1 response to ezetimibe monotherapy
24904062 DNA methylation in the promoter region of the NPC1L1 gene appears to be a major mechanism underlying differential expression of NPC1L1 along the length of the gastrointestinal tract.
24891511 Endoplasmic reticulum-associated degradation of Niemann-Pick C1: evidence for the role of heat shock proteins and identification of lysine residues that accept ubiquitin.
24861377 Our study is the first report concerning the genotype and allele frequencies of the gene coding for NPC1L1 in Japanese patients with dyslipidemia.
24554660 Herein, authors identify the host cell hepatitis C virus entry factor NPC1L1 as also being required for hepatitis C virus cell-to-cell spread.
23415434 in patients with hyperlipidemias, G allele of NPC1L1 and APO E4 could account for some of the inter-individual variability in cholesterol absorption
23139223 Glucose appears to directly modulate NPC1L1 expression via transcriptional mechanisms and the involvement of phosphatase-dependent pathways.
22646906 The present study suggests that the rs2072183 SNP in NPC1L1 gene and its association with serum lipid profiles are different between the Mulao and Han populations.
22579005 Lutein absorption is, at least in part, mediated by influx transporters NPC1L1 and SR-B1 rather than mediated by efflux transporters such as ABC (ATP-binding cassette) transporters
22095670 NPC1L1 down-regulates the expression and secretion of NPC2 by inhibiting its maturation and accelerating its degradation. Hepatic NPC1L1 may control cholesterol homeostasis via the down-regulation of NPC2.
21683156 These findings demonstrated a direct role of hepatic NPC1L1 in regulating biliary cholesterol excretion and hepatic/blood cholesterol levels, and unequivocally established hepatic NPC1L1 as a target of ezetimibe.
21602275 the mechanism of cholesterol sensing by NPC1L1 and proposes a mechanism for selective cholesterol absorption
21525977 The structure of NPC1L1(NTD) reveals a degree of flexibility surrounding the entrance to the sterol binding pocket.
21189420 dysfunction of the 19 variants on cholesterol absorption is due to the impairment of recycling, subcellular localization, glycosylation, or stability of NPC1L1
21187433 flotillins have a role in NPC1L1-mediated cholesterol uptake and NPC1L1-flotillins-postive cholesterol-enriched membrane microdomains are involved in the mechanism for efficient cholesterol absorption
20953676 PPARalpha positively regulates human NPC1L1 transcription via direct binding to a PPRE. Additionally, PGC1alpha stimulates the SREBP2/HNF4alpha- and PPARalpha/RXRalpha- mediated transactivation of human NPC1L1
20855565 Observational study of gene-disease association. (HuGE Navigator)
20686565 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
20679960 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20460578 regulation by SREBP2 and HNF1alpha on the NPC1L1 promoter activity
20379057 Single nucleotide polymorphism in NPC1L1 is associated with enhanced cholesterol absorption from the intestine.
20379057 Observational study of gene-disease association. (HuGE Navigator)
20222991 inhibition of NPC1L1 by ezetimibe is effective in non-obese patients with nonalcoholic fatty liver disease
20144195 hepatic NPC1L1 in the liver from Chinese female gallstone patients may be mediated by SREBP2
19913121 Observational study of gene-disease association. (HuGE Navigator)
19823104 The transport activity of NPC1L1 variants between cholesterol and alpha-tocopherol, were compared.
19752398 NPC1L1 gene is associated with plasma total and LDL-C levels and coronary heart disease risk.
19752398 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19747803 NPC1L1 promoter variants might explain in part the hypercholesterolemic phenotype of some subjects with non-LDL receptor/apolipoprotein B autosomal dominant hypercholesterolemia
19747803 Observational study of gene-disease association. (HuGE Navigator)
19443194 Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1
19325169 study of the topology of NPC1L1; data indicate that NPC1L1 contains 13 transmembrane helices; the NH2-terminus of NPC1L1 is in the lumen while the COOH-terminus projects to the cytosol
19265861 The -762C allele of NPC1L1 had a higher promoter activity and was associated with a higher serum total cholesterol and LDL-cholesterol level.
19265861 Observational study of gene-disease association. (HuGE Navigator)
19071091 The increased NPC1L1 and ACAT2 mRNA levels in gallstone patients might indicate an upregulated absorption and esterification of cholesterol in the small intestine.
18850127 Results describe the association between ABCG5/G8 and NPC1L1 genotype single nucleotide polymorphisms with sterol absorption and corresponding plasma concentrations.
18850127 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18783541 Expression levels of NPC1L1 were 15- to 30-fold higher in the duodenum compared with the liver at transcript and protein levels, respectively, suggesting preferential action of ezetimibe on intestinal cholesterol absorption in humans.
18641716 No common polymorphisms in ABCG8, ABCG5, or NPC1L1 were demonstrated between the 3 top responders and the non-respondersto plant sterol intervention.Yet, 1 non-responsive subject did demonstrate a rare SNP in NPC1L1.
18641716 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
18641187 the present data show that lycopene absorption is, at least in part, mediated by SR-BI but not by Niemann-Pick disease type C1, in human intestinal cells and mice.
18522832 cholesterol is internalized into cells with NPC1L1 through clathrin/AP2-mediated endocytosis and ezetimibe inhibits cholesterol absorption by blocking the internalization of NPC1L1
18522826 REVIEW: dietary cholesterol induces endocytosis of NPC1L1 at the cell surface
18413323 Cholesterol absorption was greatly reduced in individuals with NPC1L1 sequence variation.
18403720 NPC1L1 mediates alpha-tocopherol transport.
18373109 bile acids upregulate NPC1L1 mRNA and protein levels
18080173 HNF4alpha plays a crucial role in the expression and regulation of human NPC1L1 gene
18031309 NPC1L1 2/2 haplotype was associated with variation in LDL-apoB metabolism and its response to statin therapy in centrally obese men, by a mechanism that did not involve changes in VLDL-apoB kinetics, nor cholesterol synthesis or absorption.
18031309 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17662536 human NPC1L1 can functionally substitute for the Caenorhabditis elegans genes ncr-1 and/or ncr-2.
17571164 hepatic NPC1L1 may have evolved to protect the body from excessive biliary loss of cholesterol
17102949 Increased NPC1L1 and lower ABCG5 abd ABCG8 may lead to increased cholesterol and sitosterol in chylomicron particles in diabetic patients.
17005902 Small variations in ezetimibe structure or in NPC1L1 amino acid sequence can profoundly influence ezetimibe/NPC1L1 interaction and consequently their anticholesteremisc in vivo activity.
16829661 NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans
16518588 Intestinal gene expression is altred in type 2 diabetees. Diabetic patients have more NPC1L1 mRNA than the control subjects.
16449388 Observational study of gene-disease association. (HuGE Navigator)
16449388 nonsynonymous variant technique to demonstrate that genetic variation in NPC1L1 contributes to variability in cholesterol absorption and plasma levels of low-density lipoproteins
16297596 Observational study and clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
16297596 DNA sequence variants in NPC1L1 are associated with an improvement in response to ezetimibe, a cholesterol absorption inhibitor demonstrated to reduce LDL-cholesterol.
16098225 Observational study of gene-environment interaction and pharmacogenomic / toxicogenomic. (HuGE Navigator)
15671032 NPC1L1 has a role in lipid transport and in diet-induced hypercholesterolemia
14976318 expression is enriched in the small intestine and is in the brush border membrane of enterocytes

AA Sequence

MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDH      1 - 70
LILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVT     71 - 140
RVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTG    141 - 210
NGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQ    211 - 280
MPGSLVLIIILCSVFAVVTILLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVAS    281 - 350
WPLTILVLSVIPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSY    351 - 420
RYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNTSLYDCCINSL    421 - 490
LQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALALSCMADYGAPVFPFLAIGGYK    491 - 560
GKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEMRAFQRRMAGMFQVTFMAERSLEDEINRTTA    561 - 630
EDLPIFATSYIVIFLYISLALGSYSSWSRVMVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQ    631 - 700
VVPFLVLSVGADNIFIFVLEYQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVR    701 - 770
TFALTSGLAVILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFL    771 - 840
LHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPVYFVTTLGYNF    841 - 910
SSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDWLTPSSCCRLYISGPNKDKFC    911 - 980
PSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRPNIKCPKGGLAAYSTSVNLTSDGQVLDTVAI    981 - 1050
LSPRLEYSGTISAHCNLYLLDSTSRFMAYHKPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVF   1051 - 1120
PYTITNVFYEQYLTILPEGLFMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISY   1121 - 1190
NAVSLINLVSAVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQ   1191 - 1260
LIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCPNHPSRVSTAD   1261 - 1330
NIYVNHSFEGSIKGAGAISNFLPNNGRQF                                            1331 - 1359
//

Text Mined References (78)

PMID Year Title
26800364 2016 The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients.
26492642 2015 Analysis of Niemann-Pick C1-like 1 (NPC1L1) genetic polymorphisms and haplotypes in Chinese Han population.
26253792 2015 Common single nucleotide polymorphisms at the NPC1L1 gene locus significantly predict cardiovascular risk in coronary patients.
25841872 2015 Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease.
25770315 2015 Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study.
25739390 2015 Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1.
25696002 2015 NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy.
25589339 2015 Efficacy of ezetimibe is not related to NPC1L1 gene polymorphisms in a pilot study of Chilean hypercholesterolemic subjects.
25463095 2014 Genetic demonstration of intestinal NPC1L1 as a major determinant of hepatic cholesterol and blood atherogenic lipoprotein levels.
25390462 2014 Inactivating mutations in NPC1L1 and protection from coronary heart disease.
25331956 2014 The clathrin adaptor proteins ARH, Dab2, and numb play distinct roles in Niemann-Pick C1-Like 1 versus low density lipoprotein receptor-mediated cholesterol uptake.
25056759 2014 Potential effects of NPC1L1 polymorphisms in protecting against clinical disease in a chinese family with sitosterolaemia.
24974575 2014 The c.-133A > G polymorphism in NPC1L1 gene influences the efficacy of ezetimibe monotherapy on apolipoprotein A1 in hyperlipidemic patients.
24904062 2014 Epigenetic modulation of intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) gene expression by DNA methylation.
24891511 2014 Endoplasmic reticulum-associated degradation of Niemann-Pick C1: evidence for the role of heat shock proteins and identification of lysine residues that accept ubiquitin.
24861377 2014 Gene polymorphism and frequencies of the NPC1L1 gene (rs2072183, rs217434 and rs217428) in Japanese patients with dyslipidemia.
24554660 2014 Determining the involvement and therapeutic implications of host cellular factors in hepatitis C virus cell-to-cell spread.
24097068 2013 Discovery and refinement of loci associated with lipid levels.
23415434 A silent mutation of Niemann-Pick C1-like 1 and apolipoprotein E4 modulate cholesterol absorption in primary hyperlipidemias.
23139223 2013 D-Glucose modulates intestinal Niemann-Pick C1-like 1 (NPC1L1) gene expression via transcriptional regulation.
22646906 2012 Association of rs2072183 SNP and serum lipid levels in the Mulao and Han populations.
22579005 2012 Involvement of cholesterol membrane transporter Niemann-Pick C1-like 1 in the intestinal absorption of lutein.
22095670 2012 Novel function of Niemann-Pick C1-like 1 as a negative regulator of Niemann-Pick C2 protein.
21683156 2011 Ezetimibe restores biliary cholesterol excretion in mice expressing Niemann-Pick C1-Like 1 only in liver.
21602275 2011 The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake.
21525977 2011 The structure of the NPC1L1 N-terminal domain in a closed conformation.
21189420 2011 Molecular characterization of the NPC1L1 variants identified from cholesterol low absorbers.
21187433 2011 Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol uptake.
20953676 2011 Human NPC1L1 expression is positively regulated by PPAR?.
20855565 2010 Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease.
20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.
20679960 2010 Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20460578 2010 HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver.
20379057 2010 A SNP of NPC1L1 affects cholesterol absorption in Japanese.
20222991 2010 NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease.
20144195 2010 Decreased NPC1L1 expression in the liver from Chinese female gallstone patients.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19823104 2009 In-vitro characterization of the six clustered variants of NPC1L1 observed in cholesterol low absorbers.
19752398 2010 Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly.
19747803 2010 An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia.
19542231 2009 Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface.
19443194 2010 Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1: no effect of monounsaturated nor saturated fatty acids.
19325169 2009 Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption.
19265861 2009 The g.-762T>C polymorphism of the NPC1L1 gene is common in Chinese and contributes to a higher promoter activity and higher serum cholesterol levels.
19071091 2009 Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients.
18850127 2008 Genetic variation in ABC G5/G8 and NPC1L1 impact cholesterol response to plant sterols in hypercholesterolemic men.
18783541 2008 Ezetimibe prevents cholesterol gallstone formation in mice.
18641716 2008 Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study.
18641187 2008 Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann-Pick C1-like 1.
18522832 2008 The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1.
18522826 2008 Ezetimibe blocks internalization of the NPC1L1/cholesterol complex.
18413323 2008 Functional characterization of genetic variants in NPC1L1 supports the sequencing extremes strategy to identify complex trait genes.
18403720 2008 Niemann-pick C1-like 1 mediates alpha-tocopherol transport.
18373109 2008 NPC1L1 and SR-BI are involved in intestinal cholesterol absorption from small-size lipid donors.
18080173 2008 HNF4alpha is a crucial modulator of the cholesterol-dependent regulation of NPC1L1.
18031309 2008 Variation in Niemann-Pick C1-like 1 gene as a determinant of apolipoprotein B-100 kinetics and response to statin therapy in centrally obese men.
17662536 2007 Human NPC1L1 and NPC1 can functionally substitute for the ncr genes to promote reproductive development in C. elegans.
17571164 2007 Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe.
17140581 2007 Effect of ezetimibe coadministered with statins in genotype-confirmed heterozygous FH patients.
17102949 2007 Sitosterol and cholesterol in chylomicrons of type 2 diabetic and non-diabetic subjects: the relationship with ATP binding cassette proteins G5 and G8 and Niemann-Pick C1-like 1 mRNA.
17005902 2007 In vivo responsiveness to ezetimibe correlates with niemann-pick C1 like-1 (NPC1L1) binding affinity: Comparison of multiple species NPC1L1 orthologs.
16829661 2006 Localization and role of NPC1L1 in cholesterol absorption in human intestine.
16518588 2006 Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann-Pick C1-like 1, ATP-binding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein.
16449388 2006 Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels.
16297596 2005 Sequence variation in NPC1L1 and association with improved LDL-cholesterol lowering in response to ezetimibe treatment.
16098225 2005 NPC1L1 haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibe.
15928087 2005 The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1).
15790807 2005 Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution.
15679830 2005 Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe.
15671032 2005 Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia.
15604518 2005 Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14976318 2004 Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.
12853948 2003 The DNA sequence of human chromosome 7.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
10783261 2000 Evidence for a Niemann-pick C (NPC) gene family: identification and characterization of NPC1L1.