Free for academic non-profit institutions. Other users need a Commercial license

Aliases for NPC1L1 Gene

Aliases for NPC1L1 Gene

  • NPC1-Like 1 2 3
  • NPC1 (Niemann-Pick Disease, Type C1, Gene)-Like 1 2 3
  • Niemann-Pick C1-Like Protein 1 3
  • NPC11L1 3

External Ids for NPC1L1 Gene

Summaries for NPC1L1 Gene

Entrez Gene Summary for NPC1L1 Gene

  • 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]

GeneCards Summary for NPC1L1 Gene

NPC1L1 (NPC1-Like 1) is a Protein Coding gene. Diseases associated with NPC1L1 include niemann-pick disease, type c1 and abetalipoproteinemia. Among its related pathways are Metabolism and Metabolism. GO annotations related to this gene include drug binding and hedgehog receptor activity. An important paralog of this gene is PTCH2.

UniProtKB/Swiss-Prot for NPC1L1 Gene

  • 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.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NPC1L1 Gene

Genomics for NPC1L1 Gene

Genomic Location for NPC1L1 Gene

Start:
44,512,535 bp from pter
End:
44,541,315 bp from pter
Size:
28,781 bases
Orientation:
Minus strand

Genomic View for NPC1L1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NPC1L1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPC1L1 Gene

Regulatory Elements for NPC1L1 Gene

Proteins for NPC1L1 Gene

  • Protein details for NPC1L1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UHC9-NPCL1_HUMAN
    Recommended name:
    Niemann-Pick C1-like protein 1
    Protein Accession:
    Q9UHC9
    Secondary Accessions:
    • A4D2J7
    • B7ZLE6
    • D3DVK9
    • Q17RV5
    • Q6R3Q4
    • Q9UHC8

    Protein attributes for NPC1L1 Gene

    Size:
    1359 amino acids
    Molecular mass:
    148728 Da
    Quaternary structure:
    • Interacts with RAB11A, MYO5B and RAB11FIP2. Interaction with RAB11A, MYO5B and RAB11FIP2 is required for proper transport to the plasma membrane upon cholesterol depletion. Interacts with NPC2.
    Miscellaneous:
    • Target of cholesterol lowering drugs.

    Three dimensional structures from OCA and Proteopedia for NPC1L1 Gene

    Alternative splice isoforms for NPC1L1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPC1L1 Gene

Proteomics data for NPC1L1 Gene at MOPED

Post-translational modifications for NPC1L1 Gene

  • Highly glycosylated.
  • Glycosylation at Asn54, Asn132, Asn138, Asn244, Asn416, Asn431, Asn464, Asn479, Asn497, Asn506, and Asn626

Other Protein References for NPC1L1 Gene

No data available for DME Specific Peptides for NPC1L1 Gene

Domains for NPC1L1 Gene

Protein Domains for NPC1L1 Gene

InterPro:
Blocks:
ProtoNet:

UniProtKB/Swiss-Prot:

NPCL1_HUMAN
Domain:
  • Contains 1 SSD (sterol-sensing) domain.:
    • Q9UHC9
Family:
  • Belongs to the patched family.:
    • Q9UHC9
genes like me logo Genes that share domains with NPC1L1: view

No data available for Gene Families for NPC1L1 Gene

Function for NPC1L1 Gene

Molecular function for NPC1L1 Gene

UniProtKB/Swiss-Prot Function: 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.
UniProtKB/Swiss-Prot Induction: Expression is decreased in Caco-2 cells upon PPARD activation.

Gene Ontology (GO) - Molecular Function for NPC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19542231
GO:0008144 drug binding IEA --
GO:0008158 hedgehog receptor activity IEA --
GO:0017137 Rab GTPase binding IPI 19542231
GO:0031489 myosin V binding IPI 19542231
genes like me logo Genes that share ontologies with NPC1L1: view
genes like me logo Genes that share phenotypes with NPC1L1: view

Animal Models for NPC1L1 Gene

MGI Knock Outs for NPC1L1:

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for NPC1L1 Gene

Localization for NPC1L1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPC1L1 Gene

Apical cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane; Multi-pass membrane protein. Note=Subfractionation of brush border membranes from proximal enterocytes suggests considerable association with the apical membrane fraction. Exists as a predominantly cell surface membrane expressed protein (By similarity). According to PubMed:15671032, localizes in a subcellular vesicular compartment rich in RAB5. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NPC1L1 Gene COMPARTMENTS Subcellular localization image for NPC1L1 gene
Compartment Confidence
plasma membrane 5
extracellular 2
endoplasmic reticulum 1
endosome 1
nucleus 1

Gene Ontology (GO) - Cellular Components for NPC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane --
GO:0016021 integral component of membrane IDA 19325169
GO:0016324 apical plasma membrane IEA --
GO:0030659 cytoplasmic vesicle membrane IEA --
genes like me logo Genes that share ontologies with NPC1L1: view

Pathways for NPC1L1 Gene

genes like me logo Genes that share pathways with NPC1L1: view

Pathways by source for NPC1L1 Gene

1 Cell Signaling Technology pathway for NPC1L1 Gene
1 BioSystems pathway for NPC1L1 Gene

Interacting Proteins for NPC1L1 Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see details)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000289547%0d%0a9606.ENSP00000368516%0d%0a9606.ENSP00000263795%0d%0a9606.ENSP00000344818%0d%0a9606.ENSP00000304697%0d%0a9606.ENSP00000251363%0d%0a
Selected Interacting proteins: ENSP00000289547 Q9UHC9-NPCL1_HUMAN for NPC1L1 Gene via STRING I2D

Gene Ontology (GO) - Biological Process for NPC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006695 cholesterol biosynthetic process IMP 17140581
GO:0007165 signal transduction IEA --
GO:0015918 sterol transport TAS --
GO:0030299 intestinal cholesterol absorption IMP 17140581
GO:0030301 cholesterol transport IMP 17140581
genes like me logo Genes that share ontologies with NPC1L1: view

Compounds for NPC1L1 Gene

(1) Drugbank Compounds for NPC1L1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Ezetimibe
163222-33-1 target inhibitor

(6) Novoseek inferred chemical compound relationships for NPC1L1 Gene

Compound -log(P) Hits PubMed IDs
ezetimibe 89.2 22
sterol 78.2 13
cholesterol 68.2 71
lovastatin 53.8 1
lipid 39.1 3

(1) PharmGKB related drug/compound annotations for NPC1L1 Gene

Drug/compound Annotation
pravastatin CA
genes like me logo Genes that share compounds with NPC1L1: view

Transcripts for NPC1L1 Gene

Unigene Clusters for NPC1L1 Gene

NPC1-like 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NPC1L1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20a · 20b
SP1: -
SP2: - -
SP3: -

Relevant External Links for NPC1L1 Gene

GeneLoc Exon Structure for
NPC1L1
ECgene alternative splicing isoforms for
NPC1L1

Expression for NPC1L1 Gene

mRNA expression in normal human tissues for NPC1L1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NPC1L1 Gene

This gene is overexpressed in Liver (35.7).

Integrated Proteomics: protein expression from ProteomicsDB and MOPED for NPC1L1 Gene

SOURCE GeneReport for Unigene cluster for NPC1L1 Gene Hs.567486

mRNA Expression by UniProt/SwissProt for NPC1L1 Gene

Q9UHC9-NPCL1_HUMAN
Tissue specificity: Widely expressed. Expressed in liver. Also expressed in small intestine, pancreas, kidney, lung, pancreas, spleen, heart, gall bladder, brain, testis, stomach and muscle.
genes like me logo Genes that share expressions with NPC1L1: view

Orthologs for NPC1L1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NPC1L1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NPC1L1 36
  • 99.24 (n)
  • 99.19 (a)
NPC1L1 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NPC1L1 36
  • 83.52 (n)
  • 81.67 (a)
NPC1L1 37
  • 82 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NPC1L1 36
  • 83.18 (n)
  • 81.92 (a)
NPC1L1 37
  • 79 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Npc1l1 36
  • 80.03 (n)
  • 77.44 (a)
Npc1l1 16
Npc1l1 37
  • 77 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NPC1L1 37
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPC1L1 37
  • 62 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Npc1l1 36
  • 79.95 (n)
  • 78.24 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia npc1l1 36
  • 63.25 (n)
  • 60.88 (a)
zebrafish
(Danio rerio)
Actinopterygii npc1l1 36
  • 59.02 (n)
  • 55.24 (a)
npc1l1 37
  • 53 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Npc1a 37
  • 36 (a)
ManyToMany
Npc1b 37
  • 33 (a)
ManyToMany
NPC1b 38
  • 33 (a)
worm
(Caenorhabditis elegans)
Secernentea ncr-1 37
  • 25 (a)
ManyToMany
npc-1 38
  • 27 (a)
npc-2 38
  • 25 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCR1 37
  • 30 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 42 (a)
OneToOne
Species with no ortholog for NPC1L1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NPC1L1 Gene

ENSEMBL:
Gene Tree for NPC1L1 (if available)
TreeFam:
Gene Tree for NPC1L1 (if available)

Paralogs for NPC1L1 Gene

Paralogs for NPC1L1 Gene

Selected SIMAP similar genes for NPC1L1 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with NPC1L1: view

Variants for NPC1L1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NPC1L1 Gene

Q9UHC9-NPCL1_HUMAN
Variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment

Sequence variations from dbSNP and Humsavar for NPC1L1 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type MAF
rs190059 -- 44,530,142(-) ctggc(A/T)ggtct intron-variant
rs217403 -- 44,535,275(-) caatt(C/G)tcctg intron-variant
rs217404 -- 44,535,078(-) gtttt(G/T)tagtt intron-variant
rs217405 -- 44,534,367(-) TCTGG(C/T)GTGAA intron-variant
rs217406 -- 44,534,162(-) tgcta(C/G)gtagc intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NPC1L1 Gene

Variant ID Type Subtype PubMed ID
nsv523191 CNV Loss 19592680
nsv515502 CNV Loss 19592680

Relevant External Links for NPC1L1 Gene

HapMap Linkage Disequilibrium report
NPC1L1
Human Gene Mutation Database (HGMD)
NPC1L1

Disorders for NPC1L1 Gene

(1) University of Copenhagen DISEASES for NPC1L1 Gene

(1) Novoseek inferred disease relationships for NPC1L1 Gene

Disease -log(P) Hits PubMed IDs
hypercholesterolemia 39.7 3

Relevant External Links for NPC1L1

Genetic Association Database (GAD)
NPC1L1
Human Genome Epidemiology (HuGE) Navigator
NPC1L1
genes like me logo Genes that share disorders with NPC1L1: view

No data available for UniProtKB/Swiss-Prot for NPC1L1 Gene

Publications for NPC1L1 Gene

  1. 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. (PMID: 18031309) Chan D.C. … Barrett P.H. (Clin. Endocrinol. (Oxf) 2008) 3 23 49
  2. An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia. (PMID: 19747803) MartA-n B. … Civeira F. (Nutr Metab Cardiovasc Dis 2010) 3 23 49
  3. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly. (PMID: 19752398) Polisecki E. … Schaefer E.J. (J. Lipid Res. 2010) 3 23 49
  4. Association between non-responsiveness to plant sterol intervention and polymorphisms in cholesterol metabolism genes: a case-control study. (PMID: 18641716) Rudkowska I. … Jones P.J. (Appl Physiol Nutr Metab 2008) 3 23 49
  5. 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. (PMID: 19265861) Chen C.W. … Lai L.P. (J. Hum. Genet. 2009) 3 23 49

Products for NPC1L1 Gene

  • Pathway & Disease-focused RT² Profiler PCR Arrays
    • Lipoprotein Signaling & Cholesterol Metabolism in human,mouse,rat
  • QIAGEN qRT-PCR Assays for microRNAs that regulate NPC1L1
  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat
  • Predesigned siRNA for gene silencing in human,mouse,rat for NPC1L1
  • Block miRNA regulation of NPC1L1 using miScript Target Protectors

Sources for NPC1L1 Gene

Back to Top

Content