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

Gene ID: 29881, updated on 28-Oct-2019

Summary

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
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

Genomic context

See NPC1L1 in Genome Data Viewer
Location:
7p13
Exon count:
20
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (44512440..44541651, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (44552134..44580914, 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 DEAD-box helicase 56 Neighboring gene transmembrane p24 trafficking protein 4

Genomic regions, transcripts, and products

Expression

  • Project title: 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 7
MedGen: C4693795 OMIM: 617966 GeneReviews: Not available
not available

NHGRI GWAS Catalog

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

Pathways from BioSystems

  • Fat digestion and absorption, organism-specific biosystem (from KEGG)
    Fat digestion and absorption, organism-specific biosystemFat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, die...
  • Fat digestion and absorption, conserved biosystem (from KEGG)
    Fat digestion and absorption, conserved biosystemFat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, die...
  • Lipid digestion, mobilization, and transport, organism-specific biosystem (from REACTOME)
    Lipid digestion, mobilization, and transport, organism-specific biosystemProcesses annotated here include the digestion of dietary lipids, sterol uptake, the formation and turnover of lipoproteins (chylomicrons, VLDL, LDL, and HDL), and the mobilization of fatty acids thr...
  • Metabolism, organism-specific biosystem (from REACTOME)
    Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
    Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
  • Trafficking of dietary sterols, organism-specific biosystem (from REACTOME)
    Trafficking of dietary sterols, organism-specific biosystemNPC1L1 protein mediates the uptake of dietary sterols from the gut lumen. These include cholesterol and plant sterols (phytosterols). Half to two-thirds of the 250-500 milligrams of cholesterol consu...
  • Vitamin A and Carotenoid Metabolism, organism-specific biosystem (from WikiPathways)
    Vitamin A and Carotenoid Metabolism, organism-specific biosystemThis pathway is about carotenoid and vitamin A metabolism. The initial version was created by the NuGO focusteam on Carotenoid metabolism. It was used to test a text mining workflow which added some ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
Rab GTPase binding IPI
Inferred from Physical Interaction
more info
PubMed 
drug binding IEA
Inferred from Electronic Annotation
more info
 
myosin V binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
cellular response to sterol depletion IDA
Inferred from Direct Assay
more info
PubMed 
cholesterol biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
cholesterol transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
intestinal cholesterol absorption IMP
Inferred from Mutant Phenotype
more info
PubMed 
intestinal lipid absorption TAS
Traceable Author Statement
more info
 
lipoprotein metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to drug IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
apical plasma membrane IEA
Inferred from Electronic Annotation
more info
 
brush border membrane IEA
Inferred from Electronic Annotation
more info
 
cytoplasmic vesicle membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
spanning component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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)

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_001101648.2NP_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/Swiss-Prot
    Q9UHC9
    UniProtKB/TrEMBL
    A0A0C4DFX6
    Related
    ENSP00000370552.3, ENST00000381160.7
    Conserved Domains (3) summary
    TIGR00917
    Location:331266
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:661814
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:31283
    NPC1_N; Niemann-Pick C1 N terminus
  2. NM_001300967.2NP_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:33722
    2A060601; Niemann-Pick C type protein family
    pfam16414
    Location:31283
    NPC1_N; Niemann-Pick C1 N terminus
    cl21543
    Location:661722
    MMPL; MMPL family
  3. NM_013389.3NP_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
    Q9UHC9
    Related
    ENSP00000289547.4, ENST00000289547.8
    Conserved Domains (3) summary
    TIGR00917
    Location:331293
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:661814
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:31283
    NPC1_N; Niemann-Pick C1 N terminus

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

    Range
    44512440..44541651 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011515326.3XP_011513628.1  NPC1-like intracellular cholesterol transporter 1 isoform X1

    Conserved Domains (3) summary
    TIGR00917
    Location:331201
    2A060601; Niemann-Pick C type protein family
    pfam16414
    Location:31283
    NPC1_N; Niemann-Pick C1 N terminus
    cl21543
    Location:661749
    MMPL; MMPL family
  2. XM_011515328.2XP_011513630.1  NPC1-like intracellular cholesterol transporter 1 isoform X2

    Conserved Domains (2) summary
    TIGR00917
    Location:71719
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:114267
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation

RNA

  1. XR_002956423.1 RNA Sequence

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