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Aliases for NPC1 Gene

Aliases for NPC1 Gene

  • Niemann-Pick Disease, Type C1 2 3 5
  • Truncated Niemann-Pick C1 3
  • NPC 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.

  • (Microbial infection) Acts as an endosomal entry receptor for ebolavirus.

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

Promoters for NPC1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NPC1 on UCSC Golden Path with GeneCards custom track

Genomic Location for NPC1 Gene

Chromosome:
18
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

Genes around NPC1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPC1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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). Interacts with TIM1 (PubMed:25855742).
    • (Microbial infection) Interacts with ebolavirus glycoprotein.

    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 Lys 84 and Lys 585
  • Glycosylation at Asn 70, Asn 122, Asn 135, Asn 158, Asn 185, Asn 222, Asn 452, Asn 459, Asn 478, Asn 524, Asn 961, Asn 968, Asn 1064, and Asn 1072
  • Modification sites at PhosphoSitePlus

Other Protein References for NPC1 Gene

Antibody Products

No data available for DME Specific Peptides for NPC1 Gene

Domains & Families 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 :
  • 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.
  • Belongs to the patched family.
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.
UniProtKB/Swiss-Prot Function:
(Microbial infection) Acts as an endosomal entry receptor for ebolavirus.

Gene Ontology (GO) - Molecular Function for NPC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 16757520
genes like me logo Genes that share ontologies with NPC1: view
genes like me logo Genes that share phenotypes with NPC1: view

Human Phenotype Ontology for NPC1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NPC1 Gene

MGI Knock Outs for NPC1:

Animal Model Products

miRNA for NPC1 Gene

miRTarBase miRNAs that target NPC1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets 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
extracellular 5
lysosome 5
nucleus 5
plasma membrane 5
vacuole 5
endosome 4
golgi apparatus 3
cytoskeleton 1
cytosol 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for NPC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane IDA 17897319
GO:0005768 endosome IEA --
GO:0005783 endoplasmic reticulum IDA 12554680
GO:0048471 perinuclear region of cytoplasm IDA 12554680
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with NPC1: view

Pathways & Interactions for NPC1 Gene

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

Gene Ontology (GO) - Biological Process for NPC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006486 protein glycosylation IEA,IDA 10821832
GO:0007041 lysosomal transport ISS --
GO:0008206 bile acid metabolic process ISS --
GO:0031579 membrane raft organization IMP 23360953
GO:0033344 cholesterol efflux IEA,IDA 16141411
genes like me logo Genes that share ontologies with NPC1: view

No data available for SIGNOR curated interactions for NPC1 Gene

Drugs & Compounds for NPC1 Gene

(4) Drugs for NPC1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(11) Additional Compounds for NPC1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
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:

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 from HIPED for NPC1 Gene

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

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for NPC1 Gene



SOURCE GeneReport for Unigene cluster for NPC1 Gene Hs.715623

genes like me logo Genes that share expression patterns with NPC1: view

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Protein tissue co-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
chimpanzee
(Pan troglodytes)
Mammalia NPC1 36
  • 99 (a)
OneToOne
NPC1 35
  • 99.35 (n)
  • 98.98 (a)
cow
(Bos Taurus)
Mammalia NPC1 36
  • 89 (a)
OneToOne
NPC1 35
  • 84.34 (n)
  • 88.25 (a)
dog
(Canis familiaris)
Mammalia NPC1 35
  • 86.62 (n)
  • 89.42 (a)
NPC1 36
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Npc1 16
Npc1 35
  • 83.6 (n)
  • 86.61 (a)
Npc1 36
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NPC1 36
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPC1 36
  • 81 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Npc1 35
  • 83.23 (n)
  • 86.61 (a)
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
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008137 35
  • 52.14 (n)
  • 46.29 (a)
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
worm
(Caenorhabditis elegans)
Secernentea ncr-2 36
  • 25 (a)
ManyToMany
npc-1 37
  • 28 (a)
npc-2 37
  • 26 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGL008W 35
  • 45.48 (n)
  • 36.71 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCR1 35
  • 45.61 (n)
  • 36.75 (a)
NCR1 36
  • 33 (a)
OneToMany
NCR1 38
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F27137g 35
  • 46.53 (n)
  • 35.1 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G38350 35
  • 48.11 (n)
  • 40.65 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU04090 35
  • 49.5 (n)
  • 37.99 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9699 35
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

(2) 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
VAR_008815 Niemann-Pick disease C1 (NPC1)
rs1805081 - 23,560,468(-) AGTCC(A/G)TGGGA reference, missense
rs80358251 Niemann-Pick disease C1 (NPC1) 23,560,403(-) CAGCA(C/T)CATGT reference, missense
VAR_008818 -
VAR_008819 -

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

Variation tolerance for NPC1 Gene

Residual Variation Intolerance Score: 13.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 15.74; 97.34% of all genes are more intolerant (likely to be disease-causing)

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

MalaCards: The human disease database

(25) MalaCards diseases for NPC1 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

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.

Relevant External Links for NPC1

Genetic Association Database (GAD)
NPC1
Human Genome Epidemiology (HuGE) Navigator
NPC1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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 67
  2. Niemann-Pick C1 functions independently of Niemann-Pick C2 in the initial stage of retrograde transport of membrane-impermeable lysosomal cargo. (PMID: 20007703) Goldman S.D. … Krise J.P. (J. Biol. Chem. 2010) 3 23
  3. Molecular analysis of NPC1 and NPC2 gene in 34 Niemann-Pick C Italian patients: identification and structural modeling of novel mutations. (PMID: 19252935) Fancello T. … Filocamo M. (Neurogenetics 2009) 3 23
  4. Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. (PMID: 19563754) Kwon H.J. … Infante R.E. (Cell 2009) 3 23
  5. Physiological and coordinate downregulation of the NPC1 and NPC2 genes are associated with the sequestration of LDL-derived cholesterol within endocytic compartments. (PMID: 19746448) Jelinek D. … Garver W.S. (J. Cell. Biochem. 2009) 3 23

Products for NPC1 Gene

Sources for NPC1 Gene

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