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Aliases for NPC1L1 Gene

Aliases for NPC1L1 Gene

  • NPC1 Like Intracellular Cholesterol Transporter 1 2 3 5
  • NPC1 (Niemann-Pick Disease, Type C1, Gene)-Like 1 2 3
  • NPC1 Like 1 2 3
  • Niemann-Pick C1-Like Protein 1 3
  • NPC1-Like 1 2
  • 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 Intracellular Cholesterol Transporter 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 Fat digestion and absorption and Vitamin A and Carotenoid Metabolism. GO annotations related to this gene include Rab GTPase binding and myosin V binding. An important paralog of this gene is NPC1.

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 CIViC summary , 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

Enhancers for NPC1L1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH07G044308 1.3 Ensembl ENCODE dbSUPER 10.5 +231.7 231696 1.5 CTCF TFAP4 SUZ12 RAD21 ZNF316 POLR2A EGR1 SMC3 PRDM10 MAFK CAMK2B NUDCD3 NPC1L1 POLM PIR57733
GH07G044565 1 ENCODE 12.4 -24.6 -24594 1.6 HDGF ATF1 ARNT CREB3L1 ARID4B SIN3A ZNF2 ZNF48 YY1 TCF12 NPC1L1 ENSG00000228596 POLM DDX56
GH07G044288 1.1 ENCODE dbSUPER 10.4 +250.8 250810 3.4 HDAC1 ATF1 TBL1XR1 ZNF473 GATA2 SCRT2 SIRT6 FOS ZNF623 NR2F2 CAMK2B POLM NPC1L1 AEBP1 COA1 PIR57733
GH07G044377 1 Ensembl ENCODE 10.7 +160.1 160132 7.3 CTCF JUN BACH1 RARA CTBP1 ZFHX2 GATA2 POLR2A EED NR2F6 NUDCD3 CAMK2B NPC1L1 PIR57100 PIR62286
GH07G044437 0.9 ENCODE 10.6 +102.7 102667 2.6 PKNOX1 ATF1 ARNT KLF17 SIN3A ZNF2 RAD21 ZNF335 ZNF366 SCRT2 NUDCD3 RNU6-1097P NPC1L1 CAMK2B RPL32P18 PIR50224
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers 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

Post-translational modifications for NPC1L1 Gene

  • Highly glycosylated.
  • Glycosylation at Asn54, Asn132, Asn138, Asn244, Asn416, Asn431, Asn464, Asn479, posLast=497497, Asn506, and Asn626
  • Modification sites at PhosphoSitePlus

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 :
  • Belongs to the patched family.
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:0005515 protein binding IPI 19542231
GO:0008144 drug binding 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:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NPC1L1 gene
Compartment Confidence
plasma membrane 5
extracellular 2
peroxisome 1
endoplasmic reticulum 1
lysosome 1
endosome 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 IEA --
GO:0016021 integral component of membrane IEA,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 & Interactions 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

Gene Ontology (GO) - Biological Process for NPC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006695 cholesterol biosynthetic process IMP 17140581
GO:0006869 lipid transport IEA --
GO:0008202 steroid metabolic process IEA --
GO:0008203 cholesterol metabolic process IEA --
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: DrugBank, PharmGKB, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ezetimibe Approved Pharma inhibitor, Target Cholesterol transport inhibitor 279
Pravastatin Approved Pharma Competitive, Inhibitor 150
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

Drug Products

Transcripts for NPC1L1 Gene

Unigene Clusters for NPC1L1 Gene

NPC1-like 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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



NURSA nuclear receptor signaling pathways regulating expression of NPC1L1 Gene:

NPC1L1

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.

Evidence on tissue expression from TISSUES for NPC1L1 Gene

  • Liver(4.6)
  • Intestine(3.3)
  • Blood(2)
genes like me logo Genes that share expression patterns with NPC1L1: view

Primer Products

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
chimpanzee
(Pan troglodytes)
Mammalia NPC1L1 34 35
  • 99.24 (n)
cow
(Bos Taurus)
Mammalia NPC1L1 35 34
  • 83.52 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NPC1L1 34 35
  • 83.18 (n)
mouse
(Mus musculus)
Mammalia Npc1l1 34 16 35
  • 80.03 (n)
rat
(Rattus norvegicus)
Mammalia Npc1l1 34
  • 79.95 (n)
oppossum
(Monodelphis domestica)
Mammalia NPC1L1 35
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPC1L1 35
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia npc1l1 34
  • 63.25 (n)
zebrafish
(Danio rerio)
Actinopterygii npc1l1 34 35
  • 59.02 (n)
fruit fly
(Drosophila melanogaster)
Insecta Npc1a 35
  • 36 (a)
ManyToMany
NPC1b 36
  • 33 (a)
Npc1b 35
  • 33 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea npc-1 36
  • 27 (a)
npc-2 36
  • 25 (a)
ncr-1 35
  • 25 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCR1 35
  • 30 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 42 (a)
OneToOne
Species where no ortholog for NPC1L1 was found in the sources mined by GeneCards:
  • 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

NPCL1_HUMAN-Q9UHC9
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
rs119457968 drug-response 44,540,234(-) CCAAC(A/C/G/T)TGTCC reference, missense, utr-variant-5-prime
rs52815063 drug-response 44,516,100(-) CACCA(A/T)CTCTA reference, missense
rs1000099419 -- 44,529,036(+) ACTGC(A/C)CTCCA intron-variant
rs1000104535 -- 44,513,700(+) ACAGG(G/T)GAGAA intron-variant
rs1000337435 -- 44,516,448(+) CAAAA(A/G)TTAAA intron-variant

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

Variant ID Type Subtype PubMed ID
esv3613011 CNV loss 21293372
nsv1109859 CNV deletion 24896259
nsv515502 CNV loss 19592680
nsv523191 CNV loss 19592680
nsv606806 CNV loss 21841781

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

Human Gene Mutation Database (HGMD)
NPC1L1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPC1L1

Disorders for NPC1L1 Gene

MalaCards: The human disease database

(5) 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
norum disease
  • fish-eye disease
hypercholesterolemia, familial
  • hypercholesterolemia, familial, modifier of
- 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. An NPC1L1 gene promoter variant is associated with autosomal dominant hypercholesterolemia. (PMID: 19747803) MartA-n B. … Civeira F. (Nutr Metab Cardiovasc Dis 2010) 3 22 46 64
  2. 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 22 46 64
  3. 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 22 46 64
  4. 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 22 46 64
  5. 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 22 46 64

Products for NPC1L1 Gene

Sources for NPC1L1 Gene

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