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Aliases for NPC2 Gene

Aliases for NPC2 Gene

  • NPC Intracellular Cholesterol Transporter 2 2 3 5
  • Niemann-Pick Disease Type C2 Protein 3 4
  • Human Epididymis-Specific Protein 1 3 4
  • Niemann-Pick Disease, Type C2 2 3
  • Epididymal Protein 1 2 3
  • HE1 3 4
  • Tissue-Specific Secretory Protein 3
  • Epididymal Secretory Protein E1 3
  • EDDM1 3

External Ids for NPC2 Gene

Previous GeneCards Identifiers for NPC2 Gene

  • GC14M072473
  • GC14M068764
  • GC14M072936
  • GC14M074016
  • GC14M074943
  • GC14M055115

Summaries for NPC2 Gene

Entrez Gene Summary for NPC2 Gene

  • This gene encodes a protein containing a lipid recognition domain. The encoded protein may function in regulating the transport of cholesterol through the late endosomal/lysosomal system. Mutations in this gene have been associated with Niemann-Pick disease, type C2 and frontal lobe atrophy. [provided by RefSeq, Jul 2008]

GeneCards Summary for NPC2 Gene

NPC2 (NPC Intracellular Cholesterol Transporter 2) is a Protein Coding gene. Diseases associated with NPC2 include Niemann-Pick Disease, Type C2 and Niemann-Pick Disease Type C, Severe Perinatal Form. Among its related pathways are Metabolism and Immune System. GO annotations related to this gene include enzyme binding and cholesterol binding.

UniProtKB/Swiss-Prot for NPC2 Gene

  • Intracellular cholesterol transporter which acts in concert with NPC1 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. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NPC2 Gene

Genomics for NPC2 Gene

Regulatory Elements for NPC2 Gene

Enhancers for NPC2 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
GH14F074488 1.2 Ensembl ENCODE 5.7 +4.7 4725 2.3 TBP ARID4B SIN3A DMAP1 ZNF48 RARA GLIS2 GATA4 ZNF391 THAP11 ENSG00000259005 RPS2P2 SUB1P2 SYNDIG1L HEATR4 DPPA5P4 LOC105370571 LTBP2 NPC2 ISCA2
GH14F074591 1.6 FANTOM5 Ensembl ENCODE 3.2 -102.0 -102010 9.6 ATF1 PKNOX1 ZFP64 ARID4B SIN3A DMAP1 ZNF48 ZNF766 GLIS2 ELK1 PNMA1 LIN52 NEK9 FCF1 ELMSAN1 EIF2B2 AREL1 NPC2 LTBP2 LOC101928352
GH14F075399 1.2 Ensembl ENCODE 4.2 -907.2 -907221 3.6 PKNOX1 SIN3A FEZF1 ZNF2 YY1 ZNF121 GLIS2 FOS ZNF263 SP3 JDP2 NEK9 ENSG00000259005 NPC2 LINC01220
GH14F074564 1.7 FANTOM5 Ensembl ENCODE 2.6 -76.4 -76374 11.5 PKNOX1 SIN3A ARID4B FEZF1 GLI4 YY1 ZNF416 KLF7 FOS ZNF263 ELMSAN1 LTBP2 RPS2P2 SUB1P2 ENSG00000259005 FCF1 SYNDIG1L DPPA5P4 LOC105370571 NPC2
GH14F074513 1.2 FANTOM5 Ensembl ENCODE 2.3 -20.4 -20433 1.6 RFX1 L3MBTL2 IKZF1 ZBTB33 EBF1 ZIC2 NR2F2 TRIM28 ISCA2 NPC2 GC14M074212 ENSG00000258425
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around NPC2 on UCSC Golden Path with GeneCards custom track

Promoters for NPC2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001623848 1077 3001 HDGF PKNOX1 ARID4B SIN3A DMAP1 ZNF48 YY1 ZNF121 GLIS2 ZNF143

Genomic Location for NPC2 Gene

Chromosome:
14
Start:
74,476,192 bp from pter
End:
74,494,177 bp from pter
Size:
17,986 bases
Orientation:
Minus strand

Genomic View for NPC2 Gene

Genes around NPC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPC2 Gene

Proteins for NPC2 Gene

  • Protein details for NPC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P61916-NPC2_HUMAN
    Recommended name:
    Epididymal secretory protein E1
    Protein Accession:
    P61916
    Secondary Accessions:
    • B4DQV7
    • Q15668
    • Q29413

    Protein attributes for NPC2 Gene

    Size:
    151 amino acids
    Molecular mass:
    16570 Da
    Quaternary structure:
    • Interacts with NUS1/NgBR, the interaction stabilizes NCP2 and regulates cholesterol trafficking. Interacts with DHDDS. Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner (By similarity). Interacts with NEDD4L (via C2 domain) (By similarity). Interacts with NPC1L1.
    • Interacts with NUS1/NgBR, the interaction stabilizes NCP2 and regulates cholesterol trafficking. Interacts with DHDDS. Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner (By similarity). Interacts with NEDD4L (via C2 domain) (By similarity). Interacts with NPC1L1.

    Three dimensional structures from OCA and Proteopedia for NPC2 Gene

    Alternative splice isoforms for NPC2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPC2 Gene

Post-translational modifications for NPC2 Gene

  • Glycosylation at Asn 58 and Asn 135
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for NPC2 (Niemann-Pick Type C2/NPC2)

No data available for DME Specific Peptides for NPC2 Gene

Domains & Families for NPC2 Gene

Protein Domains for NPC2 Gene

Suggested Antigen Peptide Sequences for NPC2 Gene

Graphical View of Domain Structure for InterPro Entry

P61916

UniProtKB/Swiss-Prot:

NPC2_HUMAN :
  • Belongs to the NPC2 family.
Family:
  • Belongs to the NPC2 family.
genes like me logo Genes that share domains with NPC2: view

No data available for Gene Families for NPC2 Gene

Function for NPC2 Gene

Molecular function for NPC2 Gene

UniProtKB/Swiss-Prot Function:
Intracellular cholesterol transporter which acts in concert with NPC1 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. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport.
UniProtKB/Swiss-Prot Induction:
Down-regulated in response to enterovirus 71 (EV71) infection.

Gene Ontology (GO) - Molecular Function for NPC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19664597
GO:0015485 cholesterol binding IDA 17018531
GO:0019899 enzyme binding IPI 15110773
genes like me logo Genes that share ontologies with NPC2: view
genes like me logo Genes that share phenotypes with NPC2: view

Human Phenotype Ontology for NPC2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NPC2 Gene

MGI Knock Outs for NPC2:

Animal Model Products

miRNA for NPC2 Gene

miRTarBase miRNAs that target NPC2

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NPC2 Gene

Localization for NPC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPC2 Gene

Secreted. Endoplasmic reticulum. Lysosome.

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 NPC2 gene
Compartment Confidence
extracellular 5
lysosome 5
endoplasmic reticulum 4
endosome 3
plasma membrane 1
nucleus 1

Gene Ontology (GO) - Cellular Components for NPC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA --
GO:0005622 intracellular IEA --
GO:0005764 lysosome IDA 11125141
GO:0005783 endoplasmic reticulum IEA --
genes like me logo Genes that share ontologies with NPC2: view

Pathways & Interactions for NPC2 Gene

genes like me logo Genes that share pathways with NPC2: view

Gene Ontology (GO) - Biological Process for NPC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0008202 steroid metabolic process IEA --
GO:0008203 cholesterol metabolic process IEA --
GO:0009615 response to virus IEP 16548883
GO:0015914 phospholipid transport TAS 17018531
genes like me logo Genes that share ontologies with NPC2: view

No data available for SIGNOR curated interactions for NPC2 Gene

Drugs & Compounds for NPC2 Gene

(5) Drugs for NPC2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sphingosine Experimental Pharma 0
sphinganine Pharma 0
Sphingosine-1-phosphate Pharma Full agonist, Agonist endogenous second messenger and ligand for S1PR1, Endogenous agonist at S1P1-5 0

(466) Additional Compounds for NPC2 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
3-Dehydrosphinganine
  • (2S)-2-amino-1-hydroxyoctadecan-3-one
  • 1-Hydroxy-2-amino-3-oxo-octadecane
  • 2-Amino-1-hydroxy-3-Octadecanone
  • 3-Dehydro-D-sphinganine
  • 3-Dehydrosphinganine
16105-69-4
3-O-Sulfogalactosylceramide (d18:1/12:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-Sulfo-beta-D-galactosylceramide
  • 3-O-Sulfo-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
852100-88-0
3-O-Sulfogalactosylceramide (d18:1/14:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-Sulfo-beta-D-galactosylceramide
  • 3-O-Sulfo-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
3-O-Sulfogalactosylceramide (d18:1/16:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-Sulfo-beta-D-galactosylceramide
  • 3-O-Sulfo-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
862509-48-6
3-O-Sulfogalactosylceramide (d18:1/18:0)
  • 3'-O-Sulphogalactosylceramide
  • 3-O-Sulfo-beta-D-galactosylceramide
  • 3-O-Sulfo-beta-delta-galactosylceramide
  • 3-O-Sulfogalactosylceramide
  • Cerebroside 3-sulfate
244215-65-4
genes like me logo Genes that share compounds with NPC2: view

Transcripts for NPC2 Gene

Unigene Clusters for NPC2 Gene

Niemann-Pick disease, type C2:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NPC2 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5a · 5b · 5c · 5d
SP1: - -
SP2: -
SP3: - - -
SP4:
SP5: - - -

Relevant External Links for NPC2 Gene

GeneLoc Exon Structure for
NPC2
ECgene alternative splicing isoforms for
NPC2

Expression for NPC2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NPC2 Gene

Protein differential expression in normal tissues from HIPED for NPC2 Gene

This gene is overexpressed in Amniocyte (27.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for NPC2 Gene



NURSA nuclear receptor signaling pathways regulating expression of NPC2 Gene:

NPC2

SOURCE GeneReport for Unigene cluster for NPC2 Gene:

Hs.433222

mRNA Expression by UniProt/SwissProt for NPC2 Gene:

P61916-NPC2_HUMAN
Tissue specificity: Epididymis.
genes like me logo Genes that share expression patterns with NPC2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein tissue co-expression partners for NPC2 Gene

Orthologs for NPC2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NPC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NPC2 34 35
  • 99.78 (n)
dog
(Canis familiaris)
Mammalia NPC2 34 35
  • 84.81 (n)
cow
(Bos Taurus)
Mammalia NPC2 34 35
  • 83.67 (n)
rat
(Rattus norvegicus)
Mammalia Npc2 34
  • 81.95 (n)
mouse
(Mus musculus)
Mammalia Npc2 34 16 35
  • 80.09 (n)
oppossum
(Monodelphis domestica)
Mammalia NPC2 35
  • 66 (a)
OneToOne
chicken
(Gallus gallus)
Aves NPC2 34 35
  • 67.65 (n)
lizard
(Anolis carolinensis)
Reptilia NPC2 35
  • 66 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia npc2 34
  • 61.79 (n)
zebrafish
(Danio rerio)
Actinopterygii npc2 34 35
  • 61.83 (n)
NPC2 (2 of 2) 35
  • 57 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Npc2a 34 35
  • 49.87 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 45 (a)
OneToMany
-- 35
  • 45 (a)
OneToMany
Species where no ortholog for NPC2 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)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • 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)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for NPC2 Gene

ENSEMBL:
Gene Tree for NPC2 (if available)
TreeFam:
Gene Tree for NPC2 (if available)

Paralogs for NPC2 Gene

No data available for Paralogs for NPC2 Gene

Variants for NPC2 Gene

Sequence variations from dbSNP and Humsavar for NPC2 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type
rs104894458 Pathogenic, Niemann-Pick disease C2 (NPC2) [MIM:607625] 74,484,420(-) AATAT(C/T)CCTCT reference, missense
rs11694 Pathogenic, Niemann-Pick disease C2 (NPC2) [MIM:607625] 74,484,579(-) TTCAG(C/T)CTAAA reference, missense
rs143960270 Niemann-Pick disease C2 (NPC2) [MIM:607625] 74,484,500(+) TCTTA(A/C)AACCA reference, missense
rs151220873 Niemann-Pick disease C2 (NPC2) [MIM:607625], Likely pathogenic 74,486,431(+) ATCCA(C/T)AGAAC reference, missense
rs80358261 Pathogenic, Niemann-Pick disease C2 (NPC2) [MIM:607625] 74,486,404(-) TGAAT(A/G)TGAGC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for NPC2 Gene

Variant ID Type Subtype PubMed ID
esv3634943 CNV gain 21293372
nsv832829 CNV loss 17160897

Variation tolerance for NPC2 Gene

Residual Variation Intolerance Score: 59.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.64; 13.66% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NPC2 Gene

Human Gene Mutation Database (HGMD)
NPC2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPC2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPC2 Gene

Disorders for NPC2 Gene

MalaCards: The human disease database

(15) MalaCards diseases for NPC2 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

UniProtKB/Swiss-Prot

NPC2_HUMAN
  • Niemann-Pick disease C2 (NPC2) [MIM:607625]: 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 C2 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. {ECO:0000269 PubMed:11125141, ECO:0000269 PubMed:11567215, ECO:0000269 PubMed:12447927, ECO:0000269 PubMed:12955717, ECO:0000269 PubMed:15937921, ECO:0000269 PubMed:16126423}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for NPC2

Genetic Association Database (GAD)
NPC2
Human Genome Epidemiology (HuGE) Navigator
NPC2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NPC2
genes like me logo Genes that share disorders with NPC2: view

No data available for Genatlas for NPC2 Gene

Publications for NPC2 Gene

  1. Identification of HE1 as the second gene of Niemann-Pick C disease. (PMID: 11125141) Naureckiene S. … Lobel P. (Science 2000) 2 3 4 22 64
  2. Region-specific variation of gene expression in the human epididymis as revealed by in situ hybridization with tissue-specific cDNAs. (PMID: 8418812) Krull N. … Kirchhoff C. (Mol. Reprod. Dev. 1993) 2 3 4 22 64
  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 22 46 64
  4. Regulation of sterol transport between membranes and NPC2. (PMID: 18823126) Xu Z. … Storch J. (Biochemistry 2008) 3 4 22 64
  5. NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols. (PMID: 17018531) Liou H.L. … Lobel P. (J. Biol. Chem. 2006) 3 4 22 64

Products for NPC2 Gene

Sources for NPC2 Gene

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