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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

NOTCH3 Gene

protein-coding   GIFtS: 69
GCID: GC19M015270

Notch 3

(Previous names: Notch (Drosophila) homolog 3, Notch homolog 3 (Drosophila))
(Previous symbol: CADASIL)
Alzheimer's & Parkinson's Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Notch 31 2 3     Notch Homolog 3 (Drosophila)1
CADASIL1 2 5     IMF22
CASIL2 5     Neurogenic Locus Notch Homolog Protein 32
Notch (Drosophila) Homolog 31     Notch Homolog 32

External Ids:    HGNC: 78831   Entrez Gene: 48542   Ensembl: ENSG000000741817   OMIM: 6002765   UniProtKB: Q9UM473   

Export aliases for NOTCH3 gene to outside databases

Previous GC identifers: GC19M015649 GC19M015115 GC19M015131 GC19M014839


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NOTCH3 Gene:
This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein
notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an
intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands
have also been identified in human, but precise interactions between these ligands and the human notch homologues
remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (provided by RefSeq, Jul 2008)

GeneCards Summary for NOTCH3 Gene: 
NOTCH3 (notch 3) is a protein-coding gene. Diseases associated with NOTCH3 include cadasil, and balo's concentric sclerosis, and among its related super-pathways are Notch signaling pathway and Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. GO annotations related to this gene include enzyme binding and calcium ion binding. An important paralog of this gene is EYS.

UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate
determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a
transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects
the implementation of differentiation, proliferation and apoptotic programs (By similarity)

Gene Wiki entry for NOTCH3 (Notch 3) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000019.9  NT_011295.11  NC_018930.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the NOTCH3 gene promoter:
         AP-2gamma   GATA-2   C/EBPalpha   CHOP-10   Pax-3   COMP1   STAT3   AP-2beta   AP-2alpha   AP-2alphaA   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNOTCH3 promoter sequence
   Search SABiosciences Chromatin IP Primers for NOTCH3

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOTCH3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.2-p13.1   Ensembl cytogenetic band:  19p13.12   HGNC cytogenetic band: 19p13.2-p13.1

NOTCH3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH3 gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19M015270:  view genomic region     (about GC identifiers)

Start:
15,270,444 bp from pter      End:
15,311,792 bp from pter
Size:
41,349 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 (See protein sequence)
Recommended Name: Neurogenic locus notch homolog protein 3 precursor  
Size: 2321 amino acids; 243631 Da
Subunit: Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by
disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators
for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN
Subcellular location: Cell membrane; Single-pass type I membrane protein
Subcellular location: Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is
translocated to the nucleus
Secondary accessions: Q9UEB3 Q9UPL3 Q9Y6L8

Explore the universe of human proteins at neXtProt for NOTCH3: NX_Q9UM47

Explore proteomics data for NOTCH3 at MOPED 

Post-translational modifications:

  • UniProtKB: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like
    convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible
    form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding,
    it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called
    notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to
    release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity)
  • UniProtKB: Phosphorylated (By similarity)
  • UniProtKB: Hydroxylated by HIF1AN
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q9UM47

  • NOTCH3 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    NOTCH3 Protein Expression
    REFSEQ proteins: NP_000426.2  
    ENSEMBL proteins: 
     ENSP00000263388   ENSP00000470661   ENSP00000468879   ENSP00000473138  
    Reactome Protein details: Q9UM47
    Human Recombinant Protein Products for NOTCH3: 
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    Browse OriGene Protein Over-expression Lysates
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    Novus Biologicals NOTCH3 Protein
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOTCH3 

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005576extracellular region TAS--
    GO:0005654nucleoplasm TAS--
    GO:0005789endoplasmic reticulum membrane TAS--
    GO:0005829cytosol TAS--

    NOTCH3 for ontologies           About GeneDecksing



    NOTCH3 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOTCH3
    R&D Systems Antibodies for NOTCH3 (Notch-3)
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    LSBio Antibodies in human, mouse, rat for NOTCH3 

    Assay Products for NOTCH3: 
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    GenScript Custom Assay Services for NOTCH3
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NOTCH3 
    Cloud-Clone Corp. CLIAs for NOTCH3


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    ANKRD: Ankyrin repeat domain containing

    5/13 InterPro protein domains (see all 13):
     IPR024600 DUF3454_notch
     IPR008297 Notch
     IPR000742 EG-like_dom
     IPR000152 EGF-type_Asp/Asn_hydroxyl_site
     IPR018097 EGF_Ca-bd_CS

    Graphical View of Domain Structure for InterPro Entry Q9UM47

    ProtoNet protein and cluster: Q9UM47

    5 Blocks protein domains:
    IPB000152 Aspartic acid and asparagine hydroxylation site
    IPB000800 LIN-12/notch repeat (LNR) signature
    IPB001881 EGF-like calcium-binding
    IPB002049 Laminin-type EGF-like domain
    IPB002110 Ankyrin repeat signature


    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
    Similarity: Belongs to the NOTCH family
    Similarity: Contains 5 ANK repeats
    Similarity: Contains 34 EGF-like domains
    Similarity: Contains 3 LNR (Lin/Notch) repeats


    NOTCH3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NOTC3_HUMAN, Q9UM47
    Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate
    determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a
    transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects
    the implementation of differentiation, proliferation and apoptotic programs (By similarity)

         Genatlas biochemistry entry for NOTCH3:
    Drosophila Notch homolog 3,mediating cell-cell interactions that specify cell fate during development,undergoing a
    first proteolytic cleavage by furin (PACE1) in the Golgi during trafficking of Notch to the cell
    surface,undergoing further cleavage by gamma secretase (see PSEN1) releasing an intracellular domain (NICD) which
    translocates to the nucleus and modulates transcription of target genes,putatively involved in translocation with
    acute lymphoblastic/myeloblastic leukemia and in the decision between the endocrine and exocrine fates in the
    developing pancreas

         Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005509calcium ion binding IEA--
    GO:0005515protein binding IPI11101851
    GO:0019899enzyme binding IEA--
         
    NOTCH3 for ontologies           About GeneDecksing


    Phenotypes:
         15/19 MGI mutant phenotypes (inferred from 7 alleles(MGI details for Notch3) (see all 19):
     behavior/neurological  cardiovascular system  embryogenesis  endocrine/exocrine gland  growth/size 
     hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism  immune system  integument 
     mortality/aging  muscle  nervous system  normal  renal/urinary system 

    NOTCH3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for NOTCH3: Notch3tm1Khan Notch3tm1Grid

       inGenious Targeting Laboratory - Custom generated mouse model solutions for NOTCH3 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for NOTCH3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOTCH3 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOTCH3 

    miRNA
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    miRTarBase miRNAs that target NOTCH3:
    hsa-mir-206 (MIRT000665)

    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOTCH3
    8/25 QIAGEN miScript miRNA Assays for microRNAs that regulate NOTCH3 (see all 25):
    hsa-miR-26a-2* hsa-miR-875-3p hsa-miR-3673 hsa-miR-136 hsa-miR-520d-5p hsa-miR-1263 hsa-miR-300 hsa-miR-24-1*
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH3 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOTCH3


    Clone
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    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for NOTCH3 (see all 5)
    OriGene ORF clones in mouse, rat for NOTCH3
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    GenScript: all cDNA clones in your preferred vector: NOTCH3 (NM_000435)
    Browse Sino Biological Human cDNA Clones
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH3


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for NOTCH3 About   (see all 20)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Notch signaling pathway
    Notch signaling pathway0.84
    Delta-Notch Signaling Pathway0.33
    Notch Signaling Pathway0.84
    2Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant
    Signaling by NOTCH0.74
    Notch Signaling0.31
    3Signaling by NOTCH3
    Signaling by NOTCH30.83
    Pre-NOTCH Processing in the Endoplasmic Reticulum0.36
    A third proteolytic cleavage releases NICD0.43
    4Pre-NOTCH Processing in Golgi
    Pre-NOTCH Processing in Golgi0.55
    Pre-NOTCH Expression and Processing0.55
    5Generic Transcription Pathway
    Gene Expression0.47
    Generic Transcription Pathway0.47

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for NOTCH3
        Notch Signaling Pathways

    4 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for NOTCH3
        Notch Signaling
    Molecular Mechanisms of Cancer
    Presenilin-Mediated Signaling
    Epithelial Adherens Junctions

    3 Cell Signaling Technology (CST) Pathways for NOTCH3
        Wnt / Hedgehog / Notch
    Angiogenesis
    Neuroscience

    4 BioSystems Pathways for NOTCH3
        Notch Signaling Pathway
    Neural Crest Differentiation
    Delta-Notch Signaling Pathway
    Notch signaling pathway

    5/13        Reactome Pathways for NOTCH3 (see all 13)
        Pre-NOTCH Expression and Processing
    Signaling by NOTCH
    A third proteolytic cleavage releases NICD
    Generic Transcription Pathway
    NICD traffics to nucleus


    3         Kegg Pathways  (Kegg details for NOTCH3):
        Dorso-ventral axis formation
    Notch signaling pathway
    MicroRNAs in cancer


    NOTCH3 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for NOTCH3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/62 Interacting proteins for NOTCH3 (Q9UM471, 2, 3 ENSP000002633884) via UniProtKB, MINT, STRING, and/or I2D (see all 62)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CSNK2BP678702, 3MINT-8253473 I2D: score=2 
    ENSG00000206406P678702, 3MINT-8253473 I2D: score=2 
    ENSG00000224398P678702, 3MINT-8253473 I2D: score=2 
    ENSG00000224774P678702, 3MINT-8253473 I2D: score=2 
    ENSG00000228875P678702, 3MINT-8253473 I2D: score=2 
    About this table

    Gene Ontology (GO): 14 biological process terms (GO ID links to tree view) (see first 5):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006355regulation of transcription, DNA-dependent IEA--
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--
    GO:0007219Notch signaling pathway TAS--
    GO:0007220Notch receptor processing TAS--
    GO:0007275multicellular organismal development ----
    GO:0010467gene expression TAS--
    GO:0030154cell differentiation ----
    GO:0030900forebrain development IEA--
    GO:0045596negative regulation of cell differentiation ----
    GO:0045665negative regulation of neuron differentiation IEA--
    GO:0048661positive regulation of smooth muscle cell proliferation IEA--
    GO:0048663neuron fate commitment IEA--
    GO:0050793regulation of developmental process ----
    GO:0072104glomerular capillary formation IEA--

    NOTCH3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    NOTCH3 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for NOTCH3 (NOTC3)

    3 Novoseek inferred chemical compound relationships for NOTCH3 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cysteine 58.1 29 19043263 (2), 16256149 (2), 15714997 (1), 17331978 (1) (see all 18)
    arginine 14.1 3 15714997 (1), 11559313 (1)
    calcium 1.73 1 10024441 (1)

    Search CenterWatch for drugs/clinical trials and news about NOTCH3 / NOTC3

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for NOTCH3 gene: 
    NM_000435.2  

    Unigene Cluster for NOTCH3:

    Notch 3
    Hs.8546  [show with all ESTs]
    Unigene Representative Sequence: U97669
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000263388(uc002nan.3 uc002nao.1) ENST00000595514 ENST00000597756
    ENST00000601011 ENST00000600841 ENST00000595045

    miRNA
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    8/25 QIAGEN miScript miRNA Assays for microRNAs that regulate NOTCH3 (see all 25):
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      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NOTCH3

    Additional mRNA sequence: 

    AB209447.1 U97669.1 

    5 DOTS entries:

    DT.217396  DT.91963540  DT.100815125  DT.75121130  DT.91646701 

    24/277 AceView cDNA sequences (see all 277):

    CK904462 BE764071 BU846477 CB270591 AI969777 BI052410 BU859204 BM021466 
    BI523794 AI921030 BU556839 BM021193 CA446395 AA301460 AI473478 BQ919557 
    CR611252 AW194070 BU553672 CA433198 AI274902 AI091531 BM841037 AI559175 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH3    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^ 23a · 23b ^ 24 ^
    SP1:                                                                                                                    -                                       
    SP2:                                                                                      -                             -                                       
    SP3:                                                                                                                                                            

    ExUns: 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32
    SP1:                                                
    SP2:                                                
    SP3:                                                


    ECgene alternative splicing isoforms for NOTCH3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    NOTCH3 expression in normal human tissues (normalized intensities)      NOTCH3 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCAGAATAGA
    NOTCH3 Expression
    About this image


    NOTCH3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/25 selected tissues (see all 25) fully expand
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 40 entries
             Myoblasts Thoracic Primary Hypaxial Myotome
     
     Somite (Muscoskeletal System)    fully expand to see all 32 entries
             Myoblasts Thoracic Primary Hypaxial Myotome
     
     Brain (Nervous System)    fully expand to see all 15 entries
             Midbrain tegmentum
             Midbrain   
     
     Limb (Muscoskeletal System)    fully expand to see all 10 entries
             Myoblasts Forelimb Ventral Muscles
             limb/forelimb   
     
     Heart (Cardiovascular System)    fully expand to see all 5 entries
             Vascular Smooth Muscle Cells Dorsal Aorta
             heart/ventricle   

    See NOTCH3 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for NOTCH3

    SOURCE GeneReport for Unigene cluster: Hs.8546

    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
    Tissue specificity: Ubiquitously expressed in fetal and adult tissues

        SABiosciences Expression via Pathway-Focused PCR Arrays including NOTCH3: 
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              Notch Signaling Pathway in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for NOTCH3 gene from 5/12 species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Notch31 , 5 Notch gene homolog 3 (Drosophila)5
    notch 31
    84.42(n)1
    90.98(a)1
      17 (17.37 cM)5
    181311  NM_008716.21  NP_032742.11 
     321208205 
    lizard
    (Anolis carolinensis)
    Reptilia NOTCH36
    notch 3
    62(a)
    1 ↔ 1
    2(103176116-103239023)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia 1420334872   -- 76.95(n)    142033487 
    zebrafish
    (Danio rerio)
    Actinopterygii AF152001.12   -- 75.66(n)   58066  AF152001.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta SP10703 Notch binding 38(a)
    (best of 2)
      27D2   --


    ENSEMBL Gene Tree for NOTCH3 (if available)
    TreeFam Gene Tree for NOTCH3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for NOTCH3 gene
    EYS2  NOTCH42  NOTCH2NL2  NOTCH12  CRB22  NOTCH22  ENSG000002551682  CRB12  
    18/27 SIMAP similar genes for NOTCH3 using alignment to 5 protein entries:     NOTC3_HUMAN (see all proteins) (see all similar genes):
    F9    F9 p22    factor IX F9    CRB1    SVEP1    SLIT3
    PPP1R12A    NOTCH2    FBLN7    NOTCH1    PROS1    VCAN
    SLIT2    DLL3    GABPB1    SNED1    ANKRD44    EYS

    NOTCH3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1321 SNPs in NOTCH3 are shown (see all 1321)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0443044
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0443042 C Y mis40--------
    VAR_0442344
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442342 C S mis40--------
    VAR_0128904
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0128902 C Y mis40--------
    VAR_0128964
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0128962 R C mis40--------
    VAR_0442864
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442862 C R mis40--------
    VAR_0443134
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0443132 C R mis40--------
    VAR_0442694
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442692 C S mis40--------
    VAR_0442614
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442612 C S mis40--------
    VAR_0442924
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442922 C S mis40--------
    VAR_0442504
    Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)4--see VAR_0442502 C Y mis40--------

    HapMap Linkage Disequilibrium report for NOTCH3 (15270444 - 15311792 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for NOTCH3:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2718225CNV Deletion23290073
    nsv911131CNV Loss21882294
    esv997404CNV Loss20482838
    esv34154CNV Loss18971310
    nsv521424CNV Loss19592680
    nsv911132CNV Loss21882294


    Human Gene Mutation Database (HGMD): NOTCH3

    Locus Specific Mutation Databases (LSDB): NOTCH3
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 600276   
    OMIM disorders: 125310  
    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL)
    [MIM:125310]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy,
    dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. Note=The
    disease is caused by mutations affecting the gene represented in this entry

  • 20/58 diseases for NOTCH3 (see all 58):    About MalaCards
    cadasil    balo's concentric sclerosis    cerebrovascular disease    vascular dementia
    pseudobulbar palsy    migraine with aura    hemiplegic migraine    cerebritis
    migraine    varicose veins    cerebral infarction    dementia
    lymphoblastic lymphoma    arterial occlusive disease    cerebrovascular accident    hemangioma
    periodontal disease    ductal carcinoma in situ    alopecia    purpura

    5 diseases from the University of Copenhagen DISEASES database for NOTCH3:
    Cadasil     Migraine     Vascular dementia     Cerebrovascular accident
    Pseudobulbar palsy

    NOTCH3 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/27 Novoseek inferred disease relationships for NOTCH3 gene (see all 27)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cadasil 99.3 380 15857853 (5), 10766655 (5), 11391502 (5), 16580020 (5) (see all 99)
    infarct 87.7 115 18572291 (2), 12417361 (2), 16949066 (2), 16580020 (2) (see all 99)
    migraine 83 26 16492242 (6), 16426270 (3), 19018300 (2), 15313840 (1) (see all 12)
    dementia vascular 82 11 11757773 (1), 11706120 (1), 11102981 (1), 15857853 (1) (see all 10)
    dementia 76.1 27 11391502 (3), 11591842 (1), 10712431 (1), 10716263 (1) (see all 24)
    subcortical infarction 74.7 3 16580020 (1), 19242647 (1)
    infarction lacunar 74 2 17239802 (1), 12511775 (1)
    stroke 73.4 33 7783868 (2), 11591842 (1), 11757773 (1), 10712431 (1) (see all 31)
    cerebrovascular disease 66.2 13 11861701 (2), 11578869 (1), 19139365 (1), 12480758 (1) (see all 10)
    t-all 60.4 10 11891328 (2), 12524208 (1), 18032925 (1), 16838279 (1) (see all 7)

    GeneTests: NOTCH3
    GeneReviews: NOTCH3
    Genetic Association Database (GAD): NOTCH3
    Human Genome Epidemiology (HuGE) Navigator: NOTCH3 (67 documents)

    Export disorders for NOTCH3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for NOTCH3 gene, integrated from 9 sources (see all 349):
    (articles sorted by number of sources associating them with NOTCH3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. (PubMed id 16009764)1, 2, 4, 9 Peters N.... Dichgans M. (2005)
    2. CADASIL: Extended polymorphisms and mutational analysis of the NOTCH3 gene. (PubMed id 19006080)1, 4, 9 Ungaro C....Quattrone A. (2008)
    3. Investigating the association between Notch3 polymorphism and migraine. (PubMed id 16492242)1, 4, 9 Borroni B....Padovani A. (2006)
    4. Genetic, clinical and pathological studies of CADASIL in Japan: a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis. (PubMed id 12810003)1, 2, 9 Santa Y....Tabira T. (2003)
    5. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. (PubMed id 9388399)1, 2, 9 Joutel A.... Tournier-Lasserve E. (1997)
    6. Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese. (PubMed id 19242647)1, 4, 9 Lee Y.C....Soong B.W. (2009)
    7. Notch3 gene polymorphism and ischaemic cerebrovascular disease. (PubMed id 11861701)1, 4, 9 Ito D....Fukuuchi Y. (2002)
    8. Investigation of the NOTCH3 and TNFSF7 Genes on C19p13 as Candidates for Migraine. (PubMed id 19018300)1, 4, 9 Smith R.A....Griffiths L. (2008)
    9. Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and association study. (PubMed id 16426270)1, 4, 9 Schwaag S....Kuhlenbaumer G. (2006)
    10. A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings. (PubMed id 11559313)1, 2, 9 Oliveri R.L.... Quattrone A. (2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 4854 HGNC: 7883 AceView: NOTCH3 Ensembl:ENSG00000074181 euGenes: HUgn4854
    ECgene: NOTCH3 Kegg: 4854 H-InvDB: NOTCH3

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for NOTCH3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOTCH3 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOTCH3

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for NOTCH3 gene:
    Search GeneIP for patents involving NOTCH3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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