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Aliases for NPC1 Gene

Aliases for NPC1 Gene

  • Niemann-Pick Disease, Type C1 2 3
  • NPC 3 6
  • Niemann-Pick C1 Protein 3

External Ids for NPC1 Gene

Previous GeneCards Identifiers for NPC1 Gene

  • GC18M021004
  • GC18M020843
  • GC18M019363
  • GC18M019365
  • GC18M021111
  • GC18M017967

Summaries for NPC1 Gene

Entrez Gene Summary for NPC1 Gene

  • This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]

GeneCards Summary for NPC1 Gene

NPC1 (Niemann-Pick Disease, Type C1) is a Protein Coding gene. Diseases associated with NPC1 include niemann-pick disease, type c1 and niemann-pick disease type c, severe perinatal form. Among its related pathways are Lysosome and Cholesterol and Sphingolipids transport / Distribution to the intracellular membrane compartments (normal and CF). GO annotations related to this gene include receptor activity and cholesterol binding. An important paralog of this gene is NPC1L1.

UniProtKB/Swiss-Prot for NPC1 Gene

  • Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular tag team duo (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals.

Gene Wiki entry for NPC1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NPC1 Gene

Genomics for NPC1 Gene

Regulatory Elements for NPC1 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for NPC1 Gene

Start:
23,506,184 bp from pter
End:
23,586,898 bp from pter
Size:
80,715 bases
Orientation:
Minus strand

Genomic View for NPC1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NPC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPC1 Gene

Proteins for NPC1 Gene

  • Protein details for NPC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15118-NPC1_HUMAN
    Recommended name:
    Niemann-Pick C1 protein
    Protein Accession:
    O15118
    Secondary Accessions:
    • B4DET3
    • Q9P130

    Protein attributes for NPC1 Gene

    Size:
    1278 amino acids
    Molecular mass:
    142167 Da
    Quaternary structure:
    • Interacts with TMEM97. Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner (By similarity).

    Three dimensional structures from OCA and Proteopedia for NPC1 Gene

    Alternative splice isoforms for NPC1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPC1 Gene

Proteomics data for NPC1 Gene at MOPED

Post-translational modifications for NPC1 Gene

  • Glycosylated.
  • Ubiquitination at Lys84 and Lys585
  • Glycosylation at Asn70, Asn122, Asn135, Asn158, Asn185, Asn222, Asn452, Asn459, Asn478, Asn524, Asn961, Asn968, Asn1064, and Asn1072
  • Modification sites at PhosphoSitePlus

Other Protein References for NPC1 Gene

No data available for DME Specific Peptides for NPC1 Gene

Domains for NPC1 Gene

Protein Domains for NPC1 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NPC1 Gene

Graphical View of Domain Structure for InterPro Entry

O15118

UniProtKB/Swiss-Prot:

NPC1_HUMAN :
  • O15118
Domain:
  • A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes
  • Contains 1 SSD (sterol-sensing) domain.
Family:
  • Belongs to the patched family.
genes like me logo Genes that share domains with NPC1: view

No data available for Gene Families for NPC1 Gene

Function for NPC1 Gene

Molecular function for NPC1 Gene

GENATLAS Biochemistry:
glycoprotein regulator of intracellular cholesterol trafficking,predominantly expressed in perisynaptic astrocytic glial processes,homolog to the mediators of cholesterol homeostasis and to the TM region of Drosophila patched
UniProtKB/Swiss-Prot Function:
Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular tag team duo (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals.

Gene Ontology (GO) - Molecular Function for NPC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004872 receptor activity TAS 9211849
GO:0004888 transmembrane signaling receptor activity TAS 10521290
GO:0005515 protein binding IPI 16757520
GO:0008158 hedgehog receptor activity IEA --
GO:0015248 sterol transporter activity TAS 9927649
genes like me logo Genes that share ontologies with NPC1: view
genes like me logo Genes that share phenotypes with NPC1: view

Animal Models for NPC1 Gene

MGI Knock Outs for NPC1:

Animal Model Products

miRNA for NPC1 Gene

miRTarBase miRNAs that target NPC1

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NPC1

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for NPC1 Gene

Localization for NPC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPC1 Gene

Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NPC1 Gene COMPARTMENTS Subcellular localization image for NPC1 gene
Compartment Confidence
endoplasmic reticulum 5
endosome 5
lysosome 5
nucleus 5
plasma membrane 5
vacuole 5
extracellular 4
golgi apparatus 2
cytosol 1

Gene Ontology (GO) - Cellular Components for NPC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region ISS --
GO:0005635 nuclear envelope IDA 12554680
GO:0005764 lysosome ISS --
GO:0005765 lysosomal membrane IDA 17897319
GO:0005768 endosome --
genes like me logo Genes that share ontologies with NPC1: view

Pathways for NPC1 Gene

genes like me logo Genes that share pathways with NPC1: view

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Gene Ontology (GO) - Biological Process for NPC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006486 protein glycosylation IDA 10821832
GO:0006897 endocytosis IEA --
GO:0006914 autophagy IGI 19074461
GO:0007041 lysosomal transport ISS --
GO:0007165 signal transduction TAS 10521290
genes like me logo Genes that share ontologies with NPC1: view

Compounds for NPC1 Gene

(15) Novoseek inferred chemical compound relationships for NPC1 Gene

Compound -log(P) Hits PubMed IDs
u18666a 91.5 11
cholesterol 80.3 188
sterol 76.7 33
filipin 69.6 1
lipid 58.3 34
genes like me logo Genes that share compounds with NPC1: view

Transcripts for NPC1 Gene

Unigene Clusters for NPC1 Gene

Niemann-Pick disease, type C1:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NPC1

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NPC1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b · 16c ^ 17 ^ 18a · 18b ^ 19a ·
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

ExUns: 19b · 19c ^ 20a · 20b ^ 21a · 21b ^ 22a · 22b ^ 23a · 23b · 23c ^ 24a · 24b ^ 25a · 25b ^ 26
SP1: -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7: -
SP8: -
SP9:
SP10: -
SP11:
SP12:
SP13:

Relevant External Links for NPC1 Gene

GeneLoc Exon Structure for
NPC1
ECgene alternative splicing isoforms for
NPC1

Expression for NPC1 Gene

mRNA expression in normal human tissues for NPC1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues for NPC1 Gene

This gene is overexpressed in Breast (10.5), Amniocyte (8.9), and Bone (6.2).

Integrated Proteomics: protein expression from ProteomicsDB, MOPED, and MaxQB for NPC1 Gene

SOURCE GeneReport for Unigene cluster for NPC1 Gene Hs.715623

genes like me logo Genes that share expressions with NPC1: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Expression partners for NPC1 Gene

Orthologs for NPC1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NPC1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia NPC1 35
  • 84.34 (n)
  • 88.25 (a)
NPC1 36
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NPC1 35
  • 86.62 (n)
  • 89.42 (a)
NPC1 36
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Npc1 35
  • 83.6 (n)
  • 86.61 (a)
Npc1 16
Npc1 36
  • 86 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia NPC1 35
  • 99.35 (n)
  • 98.98 (a)
NPC1 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Npc1 35
  • 83.23 (n)
  • 86.61 (a)
oppossum
(Monodelphis domestica)
Mammalia NPC1 36
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPC1 36
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves NPC1 35
  • 74.23 (n)
  • 79.06 (a)
NPC1 36
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NPC1 36
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia npc1 35
  • 69.92 (n)
  • 73.1 (a)
Str.1588 35
zebrafish
(Danio rerio)
Actinopterygii npc1 35
  • 67.01 (n)
  • 69.96 (a)
wufc29a12 35
npc1 36
  • 68 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta NPC1 37
  • 43 (a)
NPC1b 37
  • 38 (a)
Npc1a 35
  • 52.08 (n)
  • 47.25 (a)
Npc1a 36
  • 45 (a)
ManyToMany
Npc1b 36
  • 38 (a)
ManyToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008137 35
  • 52.14 (n)
  • 46.29 (a)
worm
(Caenorhabditis elegans)
Secernentea npc-1 37
  • 28 (a)
npc-2 37
  • 26 (a)
ncr-2 36
  • 25 (a)
ManyToMany
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGL008W 35
  • 45.48 (n)
  • 36.71 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F27137g 35
  • 46.53 (n)
  • 35.1 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCR1 35
  • 45.61 (n)
  • 36.75 (a)
NCR1 36
  • 33 (a)
OneToMany
NCR1 38
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G38350 35
  • 48.11 (n)
  • 40.65 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9699 35
bread mold
(Neurospora crassa)
Ascomycetes NCU04090 35
  • 49.5 (n)
  • 37.99 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 50 (a)
OneToMany
CSA.1022 36
  • 55 (a)
OneToMany
Species with no ortholog for NPC1:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • 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)
  • 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NPC1 Gene

ENSEMBL:
Gene Tree for NPC1 (if available)
TreeFam:
Gene Tree for NPC1 (if available)

Paralogs for NPC1 Gene

Paralogs for NPC1 Gene

Selected SIMAP similar genes for NPC1 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with NPC1: view

Variants for NPC1 Gene

Sequence variations from dbSNP and Humsavar for NPC1 Gene

SNP ID Clin Chr 18 pos Sequence Context AA Info Type MAF
rs1140458 other 23,539,813(-) GACAA(C/G/T)TAGTC reference, synonymous-codon
rs1367084 -- 23,585,030(+) CAACA(C/G)AGCAA intron-variant
rs1429934 -- 23,582,324(+) TTTTG(C/T)TGCCA intron-variant
rs1618725 -- 23,546,988(+) AAATT(C/T)TCTTT intron-variant
rs1620047 -- 23,588,325(-) TGCAC(A/G)TCTAA upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for NPC1 Gene

Variant ID Type Subtype PubMed ID
esv34149 CNV Loss 18971310
nsv909458 CNV Gain 21882294
nsv509688 CNV Insertion 20534489
esv1106737 CNV Insertion 17803354

Relevant External Links for NPC1 Gene

HapMap Linkage Disequilibrium report
NPC1
Human Gene Mutation Database (HGMD)
NPC1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPC1 Gene

Disorders for NPC1 Gene

(1) OMIM Diseases for NPC1 Gene (607623)

UniProtKB/Swiss-Prot

NPC1_HUMAN
  • Niemann-Pick disease C1 (NPC1) [MIM:257220]: A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C1 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. An allelic variant of Niemann-Pick disease type C1 is found in people with Nova Scotia ancestry. Patients with the Nova Scotian clinical variant are less severely affected. {ECO:0000269 PubMed:10480349, ECO:0000269 PubMed:10521290, ECO:0000269 PubMed:10521297, ECO:0000269 PubMed:11182931, ECO:0000269 PubMed:11333381, ECO:0000269 PubMed:11349231, ECO:0000269 PubMed:11479732, ECO:0000269 PubMed:11545687, ECO:0000269 PubMed:11754101, ECO:0000269 PubMed:12401890, ECO:0000269 PubMed:12408188, ECO:0000269 PubMed:12554680, ECO:0000269 PubMed:12955717, ECO:0000269 PubMed:15774455, ECO:0000269 PubMed:16098014, ECO:0000269 PubMed:16126423, ECO:0000269 PubMed:16802107, ECO:0000269 PubMed:9211849, ECO:0000269 PubMed:9634529}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for NPC1 Gene

(19) Novoseek inferred disease relationships for NPC1 Gene

Disease -log(P) Hits PubMed IDs
niemann-picks disease type c 98 43
niemann-pick diseases 81.5 5
sphingolipidoses 79.7 1
lipidosis 75.8 3
neurodegeneration 63.8 7

Relevant External Links for NPC1

GeneTests
NPC1
GeneReviews
NPC1
Genetic Association Database (GAD)
NPC1
Human Genome Epidemiology (HuGE) Navigator
NPC1
genes like me logo Genes that share disorders with NPC1: view

No data available for Genatlas for NPC1 Gene

Publications for NPC1 Gene

  1. Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations. (PMID: 11479732) Ribeiro I. … Millat G. (Hum. Genet. 2001) 3 4 23 48
  2. Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein. (PMID: 10821832) Davies J.P. … Ioannou Y.A. (J. Biol. Chem. 2000) 3 4 23
  3. Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. (PMID: 9211849) Carstea E.D. … Tagle D.A. (Science 1997) 3 4 23
  4. The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1. (PMID: 9634529) Greer W.L. … Neumann P.E. (Am. J. Hum. Genet. 1998) 3 4 23
  5. Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization. (PMID: 9927649) Watari H. … Strauss J.F. III (Proc. Natl. Acad. Sci. U.S.A. 1999) 3 4 23

Products for NPC1 Gene

  • Addgene plasmids for NPC1

Sources for NPC1 Gene

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