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    NPC1L1 NPC1 like intracellular cholesterol transporter 1 [ Homo sapiens (human) ]

    Gene ID: 29881, updated on 2-Nov-2024

    Summary

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    Official Symbol
    NPC1L1provided by HGNC
    Official Full Name
    NPC1 like intracellular cholesterol transporter 1provided by HGNC
    Primary source
    HGNC:HGNC:7898
    See related
    Ensembl:ENSG00000015520 MIM:608010; AllianceGenome:HGNC:7898
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LDLCQ7; NPC11L1; SLC65A2
    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]
    Expression
    Biased expression in duodenum (RPKM 24.2), small intestine (RPKM 22.9) and 2 other tissues See more
    Orthologs
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    Genomic context

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    See NPC1L1 in Genome Data Viewer
    Location:
    7p13
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (44512535..44541330, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (44672255..44701030, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (44552134..44580929, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 1097, pseudogene Neighboring gene ribosomal protein L36a pseudogene 27 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25941 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:44579601-44580222 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:44600956-44601850 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:44605263-44605762 Neighboring gene DEAD-box helicase 56 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25942 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18145 Neighboring gene transmembrane p24 trafficking protein 4

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease. Enjoji M, et al. Lipids Health Dis, 2010 Mar 12. PMID 20222991, Free PMC Article
    2. Analysis of Niemann-Pick C1-like 1 (NPC1L1) genetic polymorphisms and haplotypes in Chinese Han population. Lou XY, et al. Pharmazie, 2015 Sep. PMID 26492642
    3. Common single nucleotide polymorphisms at the NPC1L1 gene locus significantly predict cardiovascular risk in coronary patients. Muendlein A, et al. Atherosclerosis, 2015 Sep. PMID 26253792
    4. Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease. Lauridsen BK, et al. Eur Heart J, 2015 Jul 1. PMID 25841872
    5. Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1. Lee ES, et al. BMB Rep, 2015 Sep. PMID 25739390, Free PMC Article

    See all (111) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.
      Title: NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.
    2. Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.
      Title: Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.
    3. Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease.
      Title: Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease.
    4. HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.
      Title: HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.
    5. m6A-related bioinformatics analysis and functional characterization reveals that METTL3-mediated NPC1L1 mRNA hypermethylation facilitates progression of atherosclerosis via inactivation of the MAPK pathway.
      Title: m6A-related bioinformatics analysis and functional characterization reveals that METTL3-mediated NPC1L1 mRNA hypermethylation facilitates progression of atherosclerosis via inactivation of the MAPK pathway.
    6. Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.
      Title: Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.
    7. Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.
      Title: Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.
    8. Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study.
      Title: Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study.
    9. NPC1L1-dependent transport of 27-alkyne cholesterol in intestinal epithelial cells.
      Title: NPC1L1-dependent transport of 27-alkyne cholesterol in intestinal epithelial cells.
    10. The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity.
      Title: The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity.
    Submit: New GeneRIF Correction See all GeneRIFs (98)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cholesterol binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cholesterol binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables myosin V binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables small GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables vitamin E binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to sterol depletion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cholesterol biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cholesterol homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cholesterol transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in intestinal cholesterol absorption IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intestinal cholesterol absorption IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in lipoprotein metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in sterol transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in vitamin E metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vitamin transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in apical plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasmic vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    NPC1-like intracellular cholesterol transporter 1
    Names
    NPC1 (Niemann-Pick disease, type C1, gene)-like 1
    NPC1 like 1
    niemann-Pick C1-like protein 1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013088.1 RefSeqGene

      Range
      4986..33781
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001101648.2 → NP_001095118.1  NPC1-like intracellular cholesterol transporter 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001095118.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AC004938, AF192522, AY515256
      Consensus CDS
      CCDS43575.1
      UniProtKB/TrEMBL
      A0A0C4DFX6, A0A0C4DGG6
      Related
      ENSP00000370552.3, ENST00000381160.8
      Conserved Domains (3) summary
      TIGR00917
      Location:33 → 1266
      2A060601; Niemann-Pick C type protein family
      pfam12349
      Location:661 → 814
      Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
      pfam16414
      Location:31 → 283
      NPC1_N; Niemann-Pick C1 N terminus

    2. NM_001300967.2 → NP_001287896.1  NPC1-like intracellular cholesterol transporter 1 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001287896.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several exons and its 3'-terminal exon extends past a splice site that is used in variant 1. The encoded isoform (3) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC004938, AF192523
      Consensus CDS
      CCDS75587.1
      UniProtKB/Swiss-Prot
      Q9UHC9
      Related
      ENSP00000404670.1, ENST00000423141.1
      Conserved Domains (3) summary
      TIGR00917
      Location:33 → 722
      2A060601; Niemann-Pick C type protein family
      pfam16414
      Location:31 → 283
      NPC1_N; Niemann-Pick C1 N terminus
      cl21543
      Location:661 → 722
      MMPL; MMPL family

    3. NM_013389.3 → NP_037521.2  NPC1-like intracellular cholesterol transporter 1 isoform 1 precursor

      See identical proteins and their annotated locations for NP_037521.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC004938, AF192522
      Consensus CDS
      CCDS5491.1
      UniProtKB/Swiss-Prot
      A4D2J7, B7ZLE6, D3DVK9, Q17RV5, Q6R3Q4, Q9UHC8, Q9UHC9
      UniProtKB/TrEMBL
      A0A0C4DGG6
      Related
      ENSP00000289547.4, ENST00000289547.8
      Conserved Domains (3) summary
      TIGR00917
      Location:33 → 1293
      2A060601; Niemann-Pick C type protein family
      pfam12349
      Location:661 → 814
      Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
      pfam16414
      Location:31 → 283
      NPC1_N; Niemann-Pick C1 N terminus

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      44512535..44541330 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011515326.4 → XP_011513628.1  NPC1-like intracellular cholesterol transporter 1 isoform X1

      UniProtKB/TrEMBL
      A0A0C4DGG6
      Conserved Domains (3) summary
      TIGR00917
      Location:33 → 1201
      2A060601; Niemann-Pick C type protein family
      pfam16414
      Location:31 → 283
      NPC1_N; Niemann-Pick C1 N terminus
      cl21543
      Location:661 → 749
      MMPL; MMPL family

    2. XM_011515328.3 → XP_011513630.1  NPC1-like intracellular cholesterol transporter 1 isoform X3

      Conserved Domains (2) summary
      TIGR00917
      Location:71 → 719
      2A060601; Niemann-Pick C type protein family
      pfam12349
      Location:114 → 267
      Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation

    3. XM_047420280.1 → XP_047276236.1  NPC1-like intracellular cholesterol transporter 1 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      44672255..44701030 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358018.1 → XP_054213993.1  NPC1-like intracellular cholesterol transporter 1 isoform X1

    2. XM_054358020.1 → XP_054213995.1  NPC1-like intracellular cholesterol transporter 1 isoform X3

    3. XM_054358019.1 → XP_054213994.1  NPC1-like intracellular cholesterol transporter 1 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UHC9.2 GenPept UniProtKB/Swiss-Prot:Q9UHC9

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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