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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)
 Explore 54 diseases affiliated with
NOTCH3 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for NOTCH3    

Aliases
for NOTCH3 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Notch 31 2 3     Notch Homolog 3 (Drosophila)1
CADASIL1 2 5     Neurogenic Locus Notch Homolog Protein 32
CASIL1 2 5     Notch Homolog 32
Notch (Drosophila) Homolog 31     

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


Summaries
for NOTCH3 gene

(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:
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)

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)


Genomic Views
for NOTCH3 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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000019.9  NC_018930.1  NT_011295.11  
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 plasmid: NOTCH3 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

Proteins
for NOTCH3 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
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

Post-translational modifications:

  • 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)1
  • Phosphorylated (By similarity)1
  • Hydroxylated by HIF1AN1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q9UM47

    • NOTCH3 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_000426.2  
    ENSEMBL proteins: 
     ENSP00000263388  
    Reactome Protein details: Q9UM47
    Human Recombinant Protein Products: 
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    Uscn Proteins for NOTCH3

    Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7):    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: 
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    Uscn ELISAs and CLIAs for NOTCH3

    Protein Domains /
    Families
    for NOTCH3 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    NOTCH3 for domains           About GeneDecksing

    5/13 InterPro domains/families (see all 13):
     IPR010660 Notch_NOD_dom
     IPR024600 DUF3454_notch
     IPR001881 EGF-like_Ca-bd
     IPR008297 Notch
     IPR000742 EG-like_dom

    Graphical View of Domain Structure for InterPro Entry Q9UM47

    ProtoNet protein and cluster: Q9UM47

    5 Blocks protein families:
    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


    Function
    for NOTCH3 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    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, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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)

         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

    miRNA
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    hsa-mir-206 (MIRT000665)

    OriGene 3'-UTR Clone: NOTCH3
    Browse MicroRNA Expression Plasmids
    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 plasmid: NOTCH3 3' UTR sequence
    Inhib. RNA
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    OriGene shRNA RFP: NOTCH3
    OriGene siRNA: NOTCH3
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOTCH3

    Gene Editing
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    Clone
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    Cell Line
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    In Situ Assay
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    Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004872receptor activity ----
    GO:0005509calcium ion binding IEA--
    GO:0005515protein binding IPI17292860
    GO:0019899enzyme binding IEA--


    NOTCH3 for ontologies           About GeneDecksing


    Animal Models:
         Mouse knock-outs for NOTCH3: Notch3tm1Khan Notch3tm1Grid
         15/20 MGI mutant phenotypes (inferred from 7 alleles) (MGI details for Notch3) (see all 20):
     behavior/neurological  cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland 
     growth/size  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism  immune system 
     integument  mortality/aging  muscle  nervous system  normal 

    NOTCH3 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for NOTCH3 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/19 super-pathways (see all 19) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Mature NOTCH heterodimer traffics to the plasma membrane
    		Mature NOTCH heterodimer traffics to the plasma membrane1.00
    		A third proteolytic cleavage releases NICD0.44
    		Transport of fringe-modified NOTCH to plasma membrane1.00
    		NICD traffics to nucleus0.31
    		Transport of NOTCH precursor to Golgi1.00
    		Notch-HLH transcription pathway0.31
    		Pre-NOTCH Processing in the Endoplasmic Reticulum0.67
    2Notch Signaling Pathway
    		Notch Signaling Pathway1.00
    		Delta-Notch Signaling Pathway0.27
    		Notch signaling pathway0.82
    3Generic Transcription Pathway
    		Generic Transcription Pathway1.00
    		Gene Expression0.46
    4Pre-NOTCH Processing in Golgi
    		Pre-NOTCH Processing in Golgi1.00
    		Pre-NOTCH Expression and Processing0.55
    5Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant
    		Signaling by NOTCH0.77
    		Notch Signaling0.23

    Pathway sources
    See GeneCards unified pathways
    Show all 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

    5/17        Reactome Pathways for NOTCH3 (see all 17)
        Pre-NOTCH Expression and Processing
    A third proteolytic cleavage releases NICD
    Notch-HLH transcription pathway
    NOTCH3 mRNA translation controlled by miRNAs
    Signal Transduction


    2         Kegg Pathways  (Kegg details for NOTCH3):
        Dorso-ventral axis formation
    Notch signaling pathway


    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)

    5/55 Interacting proteins for NOTCH3 (Q9UM471, 2, 3 ENSP000002633884) via UniProtKB, MINT, STRING, and/or I2D (see all 55)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    JAG1P785042, 3, ENSP000002549584MINT-8360953 I2D: score=3 STRING: ENSP00000254958
    CSNK2BP678702, 3MINT-8253473 I2D: score=2 
    JAG2Q9Y2193, ENSP000003281694I2D: score=3 STRING: ENSP00000328169
    MAML1Q925853, ENSP000002925994I2D: score=3 STRING: ENSP00000292599
    CHUKO151113, ENSP000003594244I2D: score=2 STRING: ENSP00000359424
    About this table

    Gene Ontology (GO): 5/12 biological process terms (GO ID links to tree view) (see all 12):    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:0010467gene expression TAS--


    NOTCH3 for ontologies           About GeneDecksing



    Drugs & Compounds
    for NOTCH3 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, 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
    3 Novoseek 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 

    Transcripts
    for NOTCH3 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    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, 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
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000263388(uc002nan.3 uc002nao.1)

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    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*
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    Inhib. RNA
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    Clone
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    Additional cDNA 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):

    AI274902 BM021193 BM841037 CA446395 CN483616 BU956081 BU553672 AI473478 
    BU556839 BU846477 CB270591 AI559175 AI091531 BI523794 T63511 AA301460 
    BM021466 BU859204 BI052410 AW194070 BQ919557 CR611252 BF435534 AI969777 

    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

    Expression
    for NOTCH3 gene

    (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)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GCAGAATAGA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    NOTCH3 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    10/45 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 45) 
    Tissue Anatomical Compartment CellCategory (developmental path)
    EndotheliumVeinsVascular Smooth Muscle CellsSmooth Muscle
    HeartAortic Arch ArteriesVascular Smooth Muscle CellsMyocardium, Neural Crest, Smooth Muscle
    HeartEndocardiumVascular Smooth Muscle CellsSmooth Muscle
    KidneyAfferent ArterioleJuxtaglomerular CellsKidney, Smooth Muscle
    LimbForelimb Dorsal MusclesMononuclear MyocytesSkeletal Muscle
    LimbForelimb Dorsal MusclesMyoblastsSkeletal Muscle
    LimbForelimb Ventral MusclesMononuclear MyocytesSkeletal Muscle
    LimbForelimb Ventral MusclesMyoblastsSkeletal Muscle
    LimbHindlimb Dorsal MuscleMononuclear MyocytesSkeletal Muscle
    LimbHindlimb Dorsal MuscleMyoblastsSkeletal Muscle
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 1 LifeMap Cell 
    NameCategory
    PureStem™ mesenchymal progenitor E15 (Embryonic Progenitor Cell)Adipose, Bone, Cartilage

    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: 
              Notch Signaling Targets in human mouse rat
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
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              Notch Signaling Pathway in human mouse rat

    Primer
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    Orthologs
    for NOTCH3 gene

    (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 5/19 species (see all 19)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    lizard
    (Anolis carolinensis)    		 Reptilia NOTCH36
    		 --
    		 61(a)
    		 1 ↔ 1
    		 2(103176143-103207872)
    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   --
    worm
    (Caenorhabditis elegans)    		 Secernentea W02C12.13 EGF-like protein 37(a)
    (best of 7)    		   IV(4008218-4014159)   --


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

    Paralogs
    for NOTCH3 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for NOTCH3 gene
    NOTCH42  SNED12  NOTCH12  DLL32  DLL42  JAG22  CRB22  NOTCH22  
    JAG12  DNER2  CRB12  DLL12  
    18 SIMAP similar genes for NOTCH3 using alignment to 5 protein entries:     NOTC3_HUMAN (see all proteins):
    SLIT2    ACAN    F9 p22    factor IX F9    NOTCH2    CRB1
    SVEP1    SLIT3    F9    SNED1    FBLN7    DLK2
    NOTCH1    VCAN    JAG1    EYS    CUBN    NCAN

    NOTCH3 for paralogs           About GeneDecksing



    Genomic Variants
    for NOTCH3 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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

    10/917 NCBI SNPs in NOTCH3 are shown (see all 917)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 19 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs289336981,2
    		Cpathogenic15299815(-) TCACCT/CGTATC 2 /R /C mis1 ese32Minor allele frequency- C:0.00NA 4
    rs289336971,2
    		Cpathogenic15302906(-) CCTTCC/TGCTGC 2 R C mis1 ese32Minor allele frequency- T:0.00NA 4
    rs289336961,2
    		Cpathogenic15302945(-) CCTGCC/TGCCAT 2 R C mis1 ese32Minor allele frequency- T:0.00NA 4
    rs357699761,2
    		C,F,unknown15291576(-) CTGGGG/CCCTAT 2 /P /A mis111Minor allele frequency- C:0.22NA WA EU 5179
    rs1380929381,2
    		Cother15289677(+) GACCCG/AGGCTA 2 /P /L mis11Minor allele frequency- A:0.00NA 3818
    rs1912832271,2
    		--15270003(+) ACTCAA/CTTAAC 1 -- ds50010--------
    rs1838637211,2
    		--15270035(+) GAGCCA/GAGATA 1 -- ds50010--------
    rs48090261,2
    		C,F,A,--15270059(+) TCAAGG/CAGCCA 1 -- ds50019Minor allele frequency- C:0.22NA CSA WA EA 369
    rs1391555221,2
    		--15270149(+) TCGAAC/TTGGCC 1 -- ds50010--------
    rs1499498001,2
    		--15270232(+) AGAAAA/GTTCTC 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for NOTCH3 (15270444 - 15311792 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for NOTCH3
         1 CNV: 47932
    Human Gene Mutation Database (HGMD): NOTCH3

    Locus Specific Mutation Databases (LSDB): NOTCH3

    SABiosciences Cancer Mutation PCR Assays
    1 SABiosciences qBiomarker Copy Number PCR Array containing NOTCH3:
    Oncogenes & Tumor Suppressor Genes 384HC
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing NOTCH3
    DNA2.0 Custom Variant and Variant Library Synthesis for NOTCH3

    Disorders / Diseases
    for NOTCH3 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    NOTCH3 for disorders           About GeneDecksing

    OMIM gene information: 600276   
    OMIM disorders: 125310  
    UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47
  • Defects in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and
    • leukoencephalopathy (CADASIL) [MIM:125310]. CADASIL causes a type of stroke and dementia of which key features include
    recurrent subcortical ischemic events and vascular dementia. The disorder affects relatively young adults of both
    sexes. Mutations affect highly conserved cysteine residues within epidermal growth factor (EGF)-like repeat domains in
    the extracellular part of the receptor

    20/54 diseases for NOTCH3 (see all 54):    About MalaCards
    cadasil    cerebral arteriopathy with subcortical infarcts and leukoencephalopathy    cerebritis    hemiplegic migraine
    pseudobulbar palsy    arterial occlusive disease    cerebrovascular accident    migraine
    cerebrovascular disease    cerebral infarction    dementia    migraine with aura
    acute lymphoblastic leukemia    basal cell carcinoma    multiple sclerosis    vascular dementia
    lymphoblastic leukemia    myocardial infarction    renal cell carcinoma    lymphoblastic lymphoma

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

    10/27 Novoseek 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
    CADASIL

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

    Export disorders for NOTCH3 gene to outside databases

    Publications
    for NOTCH3 gene

    (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 337):
    (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. 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)
    3. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. (PubMed id 9388399)1, 2, 9 Joutel A.... Tournier-Lasserve E. (1997)
    4. Notch3 gene polymorphism and ischaemic cerebrovascular disease. (PubMed id 11861701)1, 4, 9 Ito D....Fukuuchi Y. (2002)
    5. 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)
    6. Yield of screening for CADASIL mutations in lacunar stroke and leukoaraiosis. (PubMed id 12511775)1, 4, 9 Dong Y....Markus H.S. (2003)
    7. Lack of association between NOTCH3 gene polymorphism and cerebrovascular disease in Japanese patients. (PubMed id 12480758)1, 4, 9 Mizuno T....Nakajima K. (2002)
    8. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. (PubMed id 8878478)1, 2, 9 Joutel A.... Tournier-Lasserve E. (1996)
    9. Conserved signal peptide of Notch3 inhibits interaction with proteasome. (PubMed id 17292860)1, 2 Zhang Y.... Wang M.M. (2007)
    10. Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. (PubMed id 17573339)1, 2 Coleman M.L....Schofield C.J. (2007)

    External Searches for NOTCH3 gene

    (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)

    Genome Databases showing NOTCH3 gene

    (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

    Other Databases showing NOTCH3 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing NOTCH3 gene

    (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

    Intellectual Property
    for NOTCH3 gene

    (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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    About This Section

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