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-Like 1 2 3 5
  • NPC1 (Niemann-Pick Disease, Type C1, Gene)-Like 1 2 3
  • NPC11L1 3

External Ids for NPC1L1 Gene

Previous GeneCards Identifiers for NPC1L1 Gene

  • GC07M044198
  • GC07M044292
  • GC07M044325
  • GC07M044518
  • GC07M044552
  • GC07M044436

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 and niemann-pick disease, type c1. Among its related pathways are Lipoprotein metabolism and Metabolism. GO annotations related to this gene include Rab GTPase binding and myosin V binding. An important paralog of this gene is PTCHD3.

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

Regulatory Elements for NPC1L1 Gene

Promoters for NPC1L1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NPC1L1 on UCSC Golden Path with GeneCards custom track

Genomic Location for NPC1L1 Gene

Chromosome:
7
Start:
44,512,535 bp from pter
End:
44,541,330 bp from pter
Size:
28,796 bases
Orientation:
Minus strand

Genomic View for NPC1L1 Gene

Genes around NPC1L1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPC1L1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPC1L1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence 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 Asn 54, Asn 132, Asn 138, Asn 244, Asn 416, Asn 431, Asn 464, Asn 479, Asn 497, Asn 506, and Asn 626
  • Modification sites at PhosphoSitePlus

Other Protein References for NPC1L1 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for NPC1L1 (NPC1L1)

No data available for DME Specific Peptides for NPC1L1 Gene

Domains & Families for NPC1L1 Gene

Protein Domains for NPC1L1 Gene

InterPro:
Blocks:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

Q9UHC9

UniProtKB/Swiss-Prot:

NPCL1_HUMAN :
  • Contains 1 SSD (sterol-sensing) domain.
  • Belongs to the patched family.
Domain:
  • Contains 1 SSD (sterol-sensing) domain.
Family:
  • Belongs to the patched family.
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:0008158 hedgehog receptor activity IEA --
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:

Animal Model Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets 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
lysosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for NPC1L1 Gene

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

Pathways & Interactions for NPC1L1 Gene

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

Pathways by source 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: Q9UHC9-NPCL1_HUMAN ENSP00000289547 for NPC1L1 Gene via I2D STRING

Gene Ontology (GO) - Biological Process for NPC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006695 cholesterol biosynthetic process IMP 17140581
GO:0042157 lipoprotein metabolic process IMP 17140581
genes like me logo Genes that share ontologies with NPC1L1: view

No data available for SIGNOR curated interactions for NPC1L1 Gene

Drugs & Compounds for NPC1L1 Gene

(6) Drugs for NPC1L1 Gene - From: Novoseek, DGIdb, PharmGKB, ApexBio, DrugBank, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ezetimibe Approved Pharma inhibitor, Target Cholesterol transport inhibitor 266
Pravastatin Approved Pharma Competitive, Inhibitor 144
EMZETIBE Pharma 0

(2) Additional Compounds for NPC1L1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) ApexBio Compounds for NPC1L1 Gene

Compound Action Cas Number
Ezetimibe Cholesterol transport inhibitor 163222-33-1
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 (x35.7).

Protein differential expression in normal tissues from HIPED for NPC1L1 Gene

This gene is overexpressed in Cervix (29.7), Adrenal (9.8), and Fetal gut (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, 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 expression patterns with NPC1L1: view

Primer Products

In Situ Assay Products

No data available for Protein tissue co-expression partners for NPC1L1 Gene

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
cow
(Bos Taurus)
Mammalia NPC1L1 35
  • 83.52 (n)
  • 81.67 (a)
NPC1L1 36
  • 82 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NPC1L1 35
  • 83.18 (n)
  • 81.92 (a)
NPC1L1 36
  • 79 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Npc1l1 35
  • 80.03 (n)
  • 77.44 (a)
Npc1l1 16
Npc1l1 36
  • 77 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia NPC1L1 35
  • 99.24 (n)
  • 99.19 (a)
NPC1L1 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Npc1l1 35
  • 79.95 (n)
  • 78.24 (a)
oppossum
(Monodelphis domestica)
Mammalia NPC1L1 36
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPC1L1 36
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia npc1l1 35
  • 63.25 (n)
  • 60.88 (a)
zebrafish
(Danio rerio)
Actinopterygii npc1l1 35
  • 59.02 (n)
  • 55.24 (a)
npc1l1 36
  • 53 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta NPC1b 37
  • 33 (a)
Npc1a 36
  • 36 (a)
ManyToMany
Npc1b 36
  • 33 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea npc-1 37
  • 27 (a)
npc-2 37
  • 25 (a)
ncr-1 36
  • 25 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCR1 36
  • 30 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 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

(2) 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
VAR_023369 -
rs52815063 - 44,516,100(+) CACCA(A/T)CTCTA reference, missense
rs1468384 - 44,538,867(-) CTGAT(A/G)GGGCA reference, missense
rs217435 - 44,513,605(+) CTCCT(C/T)AGCCC reference, missense
rs190059 -- 44,530,142(-) ctggc(A/T)ggtct 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

Variation tolerance for NPC1L1 Gene

Residual Variation Intolerance Score: 67.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.11; 61.19% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NPC1L1 Gene

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

Disorders for NPC1L1 Gene

MalaCards: The human disease database

(7) MalaCards diseases for NPC1L1 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
niemann-pick disease
  • niemann-pick disease, type a
niemann-pick disease, type c1
  • niemann-pick disease, type d
pick disease
  • pick's disease
non-langerhans-cell histiocytosis
  • non-langerhans cell histiocytosis
heart disease
  • congestive heart failure
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for NPC1L1

Genetic Association Database (GAD)
NPC1L1
Human Genome Epidemiology (HuGE) Navigator
NPC1L1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NPC1L1
genes like me logo Genes that share disorders with NPC1L1: view

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

Publications for NPC1L1 Gene

  1. Evidence for a Niemann-Pick C (NPC) gene family: identification and characterization of NPC1L1. (PMID: 10783261) Davies J.P. … Ioannou Y.A. (Genomics 2000) 2 3 4 67
  2. Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe. (PMID: 15679830) Wang J. … Hegele R.A. (Clin. Genet. 2005) 3 25 26
  3. The target of ezetimibe is Niemann-Pick C1-like 1 (NPC1L1). (PMID: 15928087) Garcia-Calvo M. … Thornberry N.A. (Proc. Natl. Acad. Sci. U.S.A. 2005) 3 25 26
  4. Sterol transporters: targets of natural sterols and new lipid lowering drugs. (PMID: 15737409) Sudhop T. … von Bergmann K. (Pharmacol. Ther. 2005) 23 25 26
  5. Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption. (PMID: 14976318) Altmann S.W. … Graziano M.P. (Science 2004) 3 25 26

Products for NPC1L1 Gene

Sources for NPC1L1 Gene

Back to Top

Content