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NCSTN Gene(Protein Coding)

Nicastrin

GCID:
GC01P160343
GIFtS:
57
Genes Participants
UDN Logo

Aliases for NCSTN Gene

Aliases for NCSTN Gene

  • Nicastrin 2 3 3 5
  • Anterior Pharynx-Defective 2 3
  • ATAG1874 3
  • KIAA0253 4

External Ids for NCSTN Gene

Previous GeneCards Identifiers for NCSTN Gene

  • GC01P158105
  • GC01P156045
  • GC01P157090
  • GC01P157529
  • GC01P157126
  • GC01P158579
  • GC01P160313
  • GC01P131669

Summaries for NCSTN Gene

Entrez Gene Summary for NCSTN Gene

  • This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]

GeneCards Summary for NCSTN Gene

NCSTN (Nicastrin) is a Protein Coding gene. Diseases associated with NCSTN include Acne Inversa, Familial, 1 and Hidradenitis Suppurativa. Among its related pathways are Signaling by NOTCH1 and p75 NTR receptor-mediated signalling. Gene Ontology (GO) annotations related to this gene include peptidase activity and endopeptidase activity.

UniProtKB/Swiss-Prot for NCSTN Gene

  • Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.

Gene Wiki entry for NCSTN Gene

Additional gene information for NCSTN Gene

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

Genomics for NCSTN Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for NCSTN Gene

Promoters and enhancers for NCSTN Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH01I160341 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 594.1 -0.2 -232 3.3 HDGF PKNOX1 SMAD1 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 POLR2B NCSTN COPA SNHG28 RPSAP18 ENSG00000272668 USP21 DEDD B4GALT3 PPOX LOC100287049
GH01I161096 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 52.1 +754.4 754406 2.9 YBX1 FEZF1 IRF4 YY1 ZNF213 E2F8 ZNF416 ZNF143 ZNF548 MCM3 KLHDC9 USP21 DUSP12 PPOX LOC100287049 DEDD NCSTN RPSAP18 LOC148430 DCAF8
GH01I159908 Promoter/Enhancer 2.9 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 32.4 -425.8 -425789 18.5 CLOCK FEZF1 YBX1 IRF4 YY1 ZNF213 E2F8 ZNF143 SP3 ZC3H11A TAGLN2 GC01M159886 GC01M159919 LOC100287049 NCSTN SLAMF8 RAD1P2 ENSG00000272668 SNHG28 VSIG8
GH01I160259 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 32.4 -81.3 -81333 4.1 MLX FEZF1 DMAP1 YY1 SLC30A9 ZNF213 ZNF143 SP3 NFYC ZNF610 LOC100287049 DCAF8 GC01P160261 USP21 NCSTN PPOX ENSG00000272668 B4GALT3 RPSAP18 COPA
GH01I161130 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 28.5 +789.1 789109 3.9 FEZF1 DMAP1 YBX1 YY1 ZNF213 E2F8 ZNF416 ZNF143 ZNF548 SP3 DEDD USP21 DUSP12 PPOX LOC100287049 B4GALT3 DCAF8 NCSTN ATF6 LOC148430
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NCSTN on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NCSTN gene promoter:

Genomic Locations for NCSTN Gene

Genomic Locations for NCSTN Gene
chr1:160,343,272-160,358,952
(GRCh38/hg38)
Size:
15,681 bases
Orientation:
Plus strand
chr1:160,313,062-160,328,742
(GRCh37/hg19)

Genomic View for NCSTN Gene

Genes around NCSTN on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for NCSTN Gene

Proteins for NCSTN Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    Q92542-NICA_HUMAN
    Recommended name:
    Nicastrin
    Protein Accession:
    Q92542
    Secondary Accessions:
    • Q5T207
    • Q5T208
    • Q86VV5

    Protein attributes for NCSTN Gene

    Size:
    709 amino acids
    Molecular mass:
    78411 Da
    Quaternary structure:
    • Component of the gamma-secretase complex (PubMed:10993067). The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2 (PubMed:12740439, PubMed:25043039, PubMed:26623517, PubMed:26280335, PubMed:25918421). Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP) (PubMed:10993067). Interacts with PSEN1 and PSEN2 (PubMed:10993067).

    Three dimensional structures from OCA and Proteopedia for NCSTN Gene

    Alternative splice isoforms for NCSTN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NCSTN Gene

Protein Expression for NCSTN Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for NCSTN Gene

Other Protein References for NCSTN Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NCSTN Gene

Domains & Families for NCSTN Gene

Gene Families for NCSTN Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for NCSTN Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NCSTN Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q92542

UniProtKB/Swiss-Prot:

NICA_HUMAN :
  • Belongs to the nicastrin family.
Family:
  • Belongs to the nicastrin family.
genes like me logo Genes that share domains with NCSTN: view

Function for NCSTN Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for NCSTN Gene

UniProtKB/Swiss-Prot Function:
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.
UniProtKB/Swiss-Prot Induction:
Constitutively expressed in neural cells.

Phenotypes From GWAS Catalog for NCSTN Gene

Gene Ontology (GO) - Molecular Function for NCSTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IBA --
GO:0005515 protein binding IPI 12297508
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with NCSTN: view
genes like me logo Genes that share phenotypes with NCSTN: view

Human Phenotype Ontology for NCSTN Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NCSTN Gene

MGI Knock Outs for NCSTN:

Animal Model Products

Clone Products

  • Addgene plasmids for NCSTN

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

Localization for NCSTN Gene

Subcellular locations from UniProtKB/Swiss-Prot for NCSTN Gene

Membrane; Single-pass type I membrane protein. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

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 NCSTN gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 5
lysosome 5
golgi apparatus 5
cytoskeleton 3
mitochondrion 1
peroxisome 1
cytosol 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NCSTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane HDA,IDA 17897319
GO:0005783 endoplasmic reticulum IDA,ISS --
GO:0005794 Golgi apparatus IDA,ISS --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA,ISS --
genes like me logo Genes that share ontologies with NCSTN: view

Pathways & Interactions for NCSTN Gene

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

SIGNOR curated interactions for NCSTN Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NCSTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002262 myeloid cell homeostasis IEA --
GO:0006508 proteolysis NAS 10993067
GO:0006509 membrane protein ectodomain proteolysis IDA,ISS --
GO:0007219 Notch signaling pathway TAS --
GO:0007220 Notch receptor processing TAS 15274632
genes like me logo Genes that share ontologies with NCSTN: view

Drugs & Compounds for NCSTN Gene

Products:

  1. Drug

(5) Drugs for NCSTN Gene - From: DGIdb and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
GSI-136 Investigational Pharma 0
BMS-299897 Pharma 0
BMS-708163 Pharma 0
MK0752 Pharma inhibitor, other Notch signaling pathway inhibitor, Other 0

(1) Additional Compounds for NCSTN Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NCSTN: view

Transcripts for NCSTN Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for NCSTN Gene

(6) REFSEQ mRNAs :
(9) Additional mRNA sequences :
(514) Selected AceView cDNA sequences:
(14) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NCSTN Gene

Nicastrin:
Representative Sequences:

Clone Products

  • Addgene plasmids for NCSTN

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

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9a · 9b · 9c ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15a · 15b ^ 16a · 16b ^
SP1: - - - - - -
SP2: - - - - - - -
SP3: - - - -
SP4: -
SP5: - - - - -
SP6: - - - - - - - - - - -
SP7: - - -
SP8: - - -
SP9:
SP10:
SP11: - - -
SP12: - -
SP13: - - -
SP14:
SP15:
SP16:

ExUns: 17a · 17b · 17c ^ 18a · 18b ^ 19 ^ 20a · 20b · 20c ^ 21a · 21b · 21c ^ 22a · 22b · 22c
SP1: - - - -
SP2: - - - -
SP3: - -
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9: - - - - -
SP10: - -
SP11:
SP12:
SP13:
SP14: -
SP15:
SP16:

Relevant External Links for NCSTN Gene

GeneLoc Exon Structure for
NCSTN
ECgene alternative splicing isoforms for
NCSTN

Expression for NCSTN Gene

Products:

  1. Primer

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

mRNA expression in normal human tissues for NCSTN Gene
mRNA expression by GTEx for NCSTN GenemRNA expression by BioGPS for NCSTN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NCSTN Gene

This gene is overexpressed in Nasal epithelium (40.3).

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



Protein tissue co-expression partners for NCSTN Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of NCSTN Gene:

NCSTN

SOURCE GeneReport for Unigene cluster for NCSTN Gene:

Hs.517249

mRNA Expression by UniProt/SwissProt for NCSTN Gene:

Q92542-NICA_HUMAN
Tissue specificity: Detected in brain (at protein level) (PubMed:10993067). Widely expressed (PubMed:11396676).

Evidence on tissue expression from TISSUES for NCSTN Gene

  • Nervous system(4.6)
  • Bone marrow(4.3)
  • Liver(4.3)
  • Lung(3.4)
  • Skin(2.2)
  • Kidney(2)
  • Pancreas(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NCSTN Gene

Germ Layers:
  • ectoderm
Systems:
  • integumentary
Regions:
General:
  • skin
genes like me logo Genes that share expression patterns with NCSTN: view

No data available for mRNA differential expression in normal tissues for NCSTN Gene

Orthologs for NCSTN Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NCSTN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia NCSTN 33 34
  • 99.58 (n)
cow
(Bos Taurus)
 Mammalia NCSTN 33 34
  • 87.49 (n)
mouse
(Mus musculus)
 Mammalia Ncstn 33 16 34
  • 86.82 (n)
rat
(Rattus norvegicus)
 Mammalia Ncstn 33
  • 86.72 (n)
dog
(Canis familiaris)
 Mammalia NCSTN 33 34
  • 86.42 (n)
oppossum
(Monodelphis domestica)
 Mammalia NCSTN 34
  • 75 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia NCSTN 34
  • 64 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves NCSTN 33 34
  • 68.84 (n)
lizard
(Anolis carolinensis)
 Reptilia NCSTN 34
  • 60 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia ncstn 33
  • 63.48 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.19808 33
zebrafish
(Danio rerio)
 Actinopterygii ncstn 33
  • 59.97 (n)
CABZ01052486.1 34
  • 56 (a)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP001734 33
  • 44.25 (n)
fruit fly
(Drosophila melanogaster)
 Insecta nct 35 33 34
  • 44.08 (n)
worm
(Caenorhabditis elegans)
 Secernentea aph-2 33 34
  • 41.82 (n)
thale cress
(Arabidopsis thaliana)
 eudicotyledons AT3G52640 33
  • 40.39 (n)
rice
(Oryza sativa)
 Liliopsida Os02g0736500 33
  • 42.72 (n)
sea squirt
(Ciona savignyi)
 Ascidiacea -- 34
  • 36 (a)
 OneToOne
Species where no ortholog for NCSTN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • 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 NCSTN Gene

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

Paralogs for NCSTN Gene

No data available for Paralogs for NCSTN Gene

Variants for NCSTN Gene

Sequence variations from dbSNP and Humsavar for NCSTN Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1085307081 pathogenic, Familial acne inversa 1 160,354,238(+) C/T coding_sequence_variant, downstream_transcript_variant, genic_downstream_transcript_variant, stop_gained
rs387906896 pathogenic, Familial acne inversa 1 160,349,583(+) C/T coding_sequence_variant, stop_gained
VAR_067756 Acne inversa, familial, 1 (ACNINV1) [MIM:142690] p.Pro211Arg
rs12239747 benign, not specified 160,351,275(+) A/G/T coding_sequence_variant, intron_variant, synonymous_variant
rs1000113597 -- 160,348,757(+) T/A intron_variant

Variation tolerance for NCSTN Gene

Residual Variation Intolerance Score: 6.22% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.57; 44.71% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NCSTN Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for NCSTN Gene

Disorders for NCSTN Gene

MalaCards: The human disease database

(8) MalaCards diseases for NCSTN Gene - From: HGMD, OMIM, ClinVar, GTR, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
acne inversa, familial, 1
  • acninv1
hidradenitis suppurativa
  • acne inversa, familial
hidradenitis
  • hydradenitis
sweat gland disease
  • sweat gland diseases
alzheimer disease
  • ad
- elite association - COSMIC cancer census association via MalaCards
Search NCSTN in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NICA_HUMAN
  • Acne inversa, familial, 1 (ACNINV1) [MIM:142690]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269 PubMed:20929727, ECO:0000269 PubMed:21430701, ECO:0000269 PubMed:21495993}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NCSTN

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

No data available for Genatlas for NCSTN Gene

Publications for NCSTN Gene

  1. Analysis of the nicastrin promoter rs10752637 polymorphism and its association with Alzheimer's disease. (PMID: 19840113) Zhong L … Qing-feng L (The European journal of neuroscience 2009) 3 22 44 58
  2. Association between promoter polymorphisms of the nicastrin gene and sporadic Alzheimer's disease in North Chinese Han population. (PMID: 19394408) Ma Z … Jia J (Neuroscience letters 2009) 3 22 44 58
  3. Genetic study of Sardinian patients with Alzheimer's disease. (PMID: 16423463) Piscopo P … Confaloni A (Neuroscience letters 2006) 3 22 44 58
  4. Nicastrin gene polymorphisms, cognitive ability level and cognitive ageing. (PMID: 15567563) Deary IJ … Lovestone S (Neuroscience letters 2005) 3 22 44 58
  5. Possible association of nicastrin polymorphisms and Alzheimer disease in the Finnish population. (PMID: 15249634) Helisalmi S … Van Broeckhoven C (Neurology 2004) 3 22 44 58

Products for NCSTN Gene

  • Addgene plasmids for NCSTN