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

NOTCH4 Gene

protein-coding   GIFtS: 67
GCID: GC06M032231

Notch 4

(Previous names: Notch (Drosophila) homolog 4, Notch homolog 4 (Drosophila))
(Previous symbol: INT3)
Alzheimer's & Parkinson's Diseases Congress
  See related diseases
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(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 41 2 3     NOTCH32
INT31 2 3 5     Neurogenic Locus Notch Homolog Protein 42
Notch (Drosophila) Homolog 41     Notch Homolog 42
Notch Homolog 4 (Drosophila)1     hNotch43

External Ids:    HGNC: 78841   Entrez Gene: 48552   Ensembl: ENSG000002043017   OMIM: 1649515   UniProtKB: Q994663   

Export aliases for NOTCH4 gene to outside databases

Previous GC identifers: GC06M032185 GC06M031933 GC06M032234 GC06M032270


(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 NOTCH4 Gene:
This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share
structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like
(EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members
play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling
network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between
physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate)
establishes an intercellular signaling pathway that plays a key role in development. Homologues of the
notch-ligands have also been identified in human, but precise interactions between these ligands and the human
notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on
the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play
a role in vascular, renal and hepatic development. This gene may be associated with susceptibility to
schizophrenia in a small portion of cases. An alternative splice variant has been described but its biological
nature has not been determined. (provided by RefSeq, Jul 2008)

GeneCards Summary for NOTCH4 Gene: 
NOTCH4 (notch 4) is a protein-coding gene. Diseases associated with NOTCH4 include pseudobulbar palsy, and schizoaffective disorder, 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 receptor activity and calcium ion binding. An important paralog of this gene is EYS.

UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
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. May regulate branching morphogenesis
in the developing vascular system (By similarity)

Gene Wiki entry for NOTCH4 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_000006.11  NT_007592.15  NT_113891.2  NT_167246.1  NT_167247.1  NT_167248.1  NT_167249.1  NC_018917.2  
NT_167244.1  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the NOTCH4 gene promoter:
         p53   MyoD   Tal-1beta   PPAR-alpha   HEN1   Ik-2   NF-kappaB1   ITF-2   ATF6   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): NOTCH4 promoter sequence
   Search SABiosciences Chromatin IP Primers for NOTCH4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOTCH4


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

Entrez Gene cytogenetic band: 6p21.3   Ensembl cytogenetic band:  6p21.32   HGNC cytogenetic band: 6p21.3

NOTCH4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH4 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06M032231:  view genomic region     (about GC identifiers)

Start:
32,162,620 bp from pter      End:
32,191,844 bp from pter
Size:
29,225 bases      Orientation:
minus strand

6 alternative locations:
Chr6-,NT_167247 3,542,444-3,571,691      Chr6-,NT_167246 3,505,441-3,534,689      Chr6-,NT_113891.2 3,633,298-3,662,520     
Chr6-,NT_167248 3,423,638-3,452,865      Chr6-,NT_167244 3,477,358-3,486,924      Chr6-,NT_167249 3,510,346-3,539,573     

(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: NOTC4_HUMAN, Q99466 (See protein sequence)
Recommended Name: Neurogenic locus notch homolog protein 4 precursor  
Size: 2003 amino acids; 209622 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 NOTCH4
Subcellular location: Cell membrane; Single-pass type I membrane protein
Subcellular location: Notch 4 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is
translocated to the nucleus
Sequence caution: Sequence=BAA09708.1; Type=Frameshift; Positions=1438, 1463;
Secondary accessions: B0V183 B0V1X5 O00306 Q5SSY7 Q99458 Q99940 Q9H3S8 Q9UII9 Q9UIJ0
Alternative splicing: 3 isoforms:  Q99466-1   Q99466-2   Q99466-3   

Explore the universe of human proteins at neXtProt for NOTCH4: NX_Q99466

Explore proteomics data for NOTCH4 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)
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q99466

  • NOTCH4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    NOTCH4 Protein Expression
    REFSEQ proteins: NP_004548.3  
    ENSEMBL proteins: 
     ENSP00000364163   ENSP00000398123  
    Reactome Protein details: Q99466
    Human Recombinant Protein Products for NOTCH4: 
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    OriGene Protein Over-expression Lysate for NOTCH4
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    Novus Biologicals NOTCH4 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOTCH4 

    Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005576extracellular region TAS--
    GO:0005634nucleus TAS8681805
    GO:0005654nucleoplasm TAS--
    GO:0005789endoplasmic reticulum membrane TAS--

    NOTCH4 for ontologies           About GeneDecksing



    NOTCH4 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOTCH4
    R&D Systems Antibodies for NOTCH4 (Notch-4)
    Cell Signaling Technology (CST) Antibodies for NOTCH4 
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    Novus Biologicals NOTCH4 Antibodies
    Abcam antibodies for NOTCH4
    Cloud-Clone Corp. Antibodies for NOTCH4 
    ThermoFisher Antibodies for NOTCH4
    LSBio Antibodies in human, mouse, rat for NOTCH4 

    Assay Products for NOTCH4: 
    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for NOTCH4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NOTCH4 
    Cloud-Clone Corp. CLIAs for NOTCH4


    (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

    5/11 InterPro protein domains (see all 11):
     IPR008297 Notch
     IPR000742 EG-like_dom
     IPR022355 Notch_4
     IPR000152 EGF-type_Asp/Asn_hydroxyl_site
     IPR018097 EGF_Ca-bd_CS

    Graphical View of Domain Structure for InterPro Entry Q99466

    ProtoNet protein and cluster: Q99466

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


    UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
    Similarity: Belongs to the NOTCH family
    Similarity: Contains 5 ANK repeats
    Similarity: Contains 29 EGF-like domains
    Similarity: Contains 3 LNR (Lin/Notch) repeats


    NOTCH4 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: NOTC4_HUMAN, Q99466
    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. May regulate branching morphogenesis
    in the developing vascular system (By similarity)

         Genatlas biochemistry entry for NOTCH4:
    Drosophila Notch homolog 4,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,homologous to MMTV integration site
    int-3,containing a (CTG)n repeats polymorphism,with 2 isoforms L and S

         Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004872receptor activity TAS11823422
    GO:0005509calcium ion binding TAS11823422
    GO:0005515protein binding IPI11101851
    GO:0046982protein heterodimerization activity TAS8681805
         
    NOTCH4 for ontologies           About GeneDecksing


    Phenotypes:
         6 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Notch4):
     cardiovascular system  embryogenesis  growth/size  homeostasis/metabolism  nervous system 
     normal 

    NOTCH4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Notch4tm1Grid for NOTCH4

       inGenious Targeting Laboratory - Custom generated mouse model solutions for NOTCH4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for NOTCH4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOTCH4 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOTCH4 

    miRNA
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    miRTarBase miRNAs that target NOTCH4:
    hsa-mir-181c (MIRT003211)

    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOTCH4
    6 QIAGEN miScript miRNA Assays for microRNAs that regulate NOTCH4:
    hsa-miR-221* hsa-miR-4265 hsa-miR-607 hsa-miR-218-1* hsa-miR-3945 hsa-miR-4296
    SwitchGear 3'UTR luciferase reporter plasmidNOTCH4 3' UTR sequence
    Inhib. RNA
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    Gene Editing
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    Clone
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    OriGene ORF clones in mouse, rat for NOTCH4
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    GenScript: all cDNA clones in your preferred vector: NOTCH4 (NM_004557)
    Browse Sino Biological Human cDNA Clones
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOTCH4

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH4


    (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 NOTCH4 About   (see all 21)                                                                                              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 NOTCH40.83
    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 EMD Millipore Pathway for NOTCH4
        Selected targets of GCR-alpha

    1 R&D Systems Pathway for NOTCH4
        Notch Signaling Pathways

    4 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for NOTCH4
        Notch Signaling
    Molecular Mechanisms of Cancer
    Presenilin-Mediated Signaling
    Epithelial Adherens Junctions

    3 Cell Signaling Technology (CST) Pathways for NOTCH4
        Wnt / Hedgehog / Notch
    Angiogenesis
    Neuroscience

    4 BioSystems Pathways for NOTCH4
        Notch Signaling Pathway
    Neural Crest Differentiation
    Delta-Notch Signaling Pathway
    Notch signaling pathway

    5/13        Reactome Pathways for NOTCH4 (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 NOTCH4):
        Dorso-ventral axis formation
    Notch signaling pathway
    MicroRNAs in cancer


    NOTCH4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for NOTCH4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 12)

    5/19 Interacting proteins for NOTCH4 (Q994662, 3 ENSP000003641634) via UniProtKB, MINT, STRING, and/or I2D (see all 19)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SMAD2Q157963, ENSP000002621604I2D: score=3 STRING: ENSP00000262160
    SMAD3P840223, ENSP000003329734I2D: score=3 STRING: ENSP00000332973
    MAML1Q925853, ENSP000002925994I2D: score=2 STRING: ENSP00000292599
    DLL4Q9NR613, ENSP000002497494I2D: score=1 STRING: ENSP00000249749
    PSEN1P497683, ENSP000003263664I2D: score=1 STRING: ENSP00000326366
    About this table

    Gene Ontology (GO): 5/19 biological process terms (GO ID links to tree view) (see all 19):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001569patterning of blood vessels ISS--
    GO:0001709cell fate determination TAS11823422
    GO:0001763morphogenesis of a branching structure ISS--
    GO:0001886endothelial cell morphogenesis IEA--
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--

    NOTCH4 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

    NOTCH4 for compounds           About GeneDecksing

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

    Browse Tocris compounds for NOTCH4 (NOTC4)

    2 Novoseek inferred chemical compound relationships for NOTCH4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    snp 2 74.2 3 11239712 (2), 15653273 (1)
    vegf 29.9 5 16951162 (3), 18671974 (1), 17955263 (1)

    Search CenterWatch for drugs/clinical trials and news about NOTCH4 / NOTC4

    (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 NOTCH4 gene: 
    NM_004557.3  

    Unigene Cluster for NOTCH4:

    Notch 4
    Hs.436100  [show with all ESTs]
    Unigene Representative Sequence: NM_004557
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000491215 ENST00000474612(uc011dpt.2 uc003oba.3 uc011dpw.1)
    ENST00000375023(uc003obb.3 uc011dpu.2 uc011dpv.2) ENST00000465528
    ENST00000473562(uc003obc.3) ENST00000443903

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    SwitchGear 3'UTR luciferase reporter plasmidNOTCH4 3' UTR sequence
    Inhib. RNA
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      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NOTCH4

    Additional mRNA sequence: 

    AK131314.1 AK290785.1 AK293692.1 AK294161.1 BC033869.1 BC063815.1 BC140782.1 BC144540.1 
    BC144541.1 D63395.1 U95299.1 

    6 DOTS entries:

    DT.443558  DT.97785448  DT.40281802  DT.121378239  DT.99962397  DT.91906043 

    24/222 AceView cDNA sequences (see all 222):

    AI673445 BQ183096 BC063815 BG743359 BQ023076 AI300614 BQ053714 AA868548 
    AJ243938 AA984885 BC018724 AJ243937 AI244789 AJ705578 NM_022107 BU146559 
    CD672916 BQ023880 BQ711693 BP368231 BC033869 CK821917 AK131314 CR604341 

    GeneLoc Exon Structure


    (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

    NOTCH4 expression in normal human tissues (normalized intensities)      NOTCH4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GTAGGGAGGA
    NOTCH4 Expression
    About this image


    NOTCH4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/6 selected tissues (see all 6) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 3 entries
             Angioblasts Embryonic Capillary Plexus
     
     Lateral Plate Mesoderm (Gastrulation Derivatives)    fully expand to see all 3 entries
             Angioblasts Embryonic Capillary Plexus
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Myoblasts Mandibular Arch Muscles
     
     Placenta (Extraembryonic Tissues)
             Extravillous Cytotrophoblast Cells Extravillous Cytotrophoblast Layer
     
     Blood (Cardiovascular System)
             Conventional Dendritic Cells I Spleen

    See NOTCH4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for NOTCH4

    SOURCE GeneReport for Unigene cluster: Hs.436100

    UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
    Tissue specificity: Highly expressed in the heart, moderately in the lung and placenta and at low levels in the
    liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression
    was seen in adult brain or peripheral blood leukocytes

        SABiosciences Expression via Pathway-Focused PCR Arrays including NOTCH4 (see all 7): 
              Adherens Junctions in human mouse rat
              Stem Cell Signaling in human mouse rat
              Neurotoxicity in human mouse rat
              Cell Junction PathwayFinder in human mouse rat
              Angiogenesis 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 NOTCH4 gene from 5/11 species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Notch41 , 5 Notch gene homolog 4 (Drosophila)5
    notch 41
    83.13(n)1
    82.29(a)1
      17 (18.15 cM)5
    181321  NM_010929.21  NP_035059.21 
     345642685 
    chicken
    (Gallus gallus)
    Aves EYS6
    Uncharacterized protein
    34(a)
    1 ↔ 1
    3(84449717-84579680)
    lizard
    (Anolis carolinensis)
    Reptilia NOTCH46
    Uncharacterized protein
    39(a)
    1 ↔ 1
    2(198816928-198859587)
    zebrafish
    (Danio rerio)
    Actinopterygii NOTCH46
    notch 4
    39(a)
    1 ↔ 1
    13(38305655-38437169)
    worm
    (Caenorhabditis elegans)
    Secernentea W02C12.13 EGF-like protein 33(a)
    (best of 5)
      IV(4008218-4014159)   --


    ENSEMBL Gene Tree for NOTCH4 (if available)
    TreeFam Gene Tree for NOTCH4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for NOTCH4 gene
    EYS2  NOTCH2NL2  NOTCH12  NOTCH32  CRB22  NOTCH22  ENSG000002551682  CRB12  
    6 SIMAP similar genes for NOTCH4 using alignment to 6 protein entries:     NOTC4_HUMAN (see all proteins):
    F9    NOTCH3    NOTCH2    DKFZp761E1322    MTPN    CRB1

    NOTCH4 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

    UniProtKB/Swiss-Prot: NOTC4_HUMAN, Q99466
    Polymorphism: The poly-Leu region of NOTCH4 (in the signal peptide) is polymorphic and the number of Leu varies in
    the population (from 6 to 12)


    10/868 SNPs in NOTCH4 are shown (see all 868)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0128684
    ----see VAR_0128682 E Q mis40--------
    rs615808651,2
    C--31947501(+) TTTTT-/TT/TTT
            
    GAGAC
    2 -- us2k1 cds10--------
    rs1463951611,2
    --32079741(+) GCGACA/GGAGGG 1 -- ds50010--------
    rs1816602001,2
    --32079751(+) GCTGGA/TTTCAG 1 -- ds50010--------
    rs1384577081,2
    --32079791(+) GCATTA/GGATTC 1 -- ds50010--------
    rs1415752601,2
    --32079793(+) ATTAGA/CTTCCC 1 -- ds50010--------
    rs1389861661,2
    C--32079889(+) CTGAC-/AGGAGGTG 1 -- ds50010--------
    rs1863157841,2
    --32080133(+) ATGCTA/GAGCCA 1 -- ds50010--------
    rs455920331,2
    C,F--32080155(+) TGCTGA/GCATTA 1 -- ds50013Minor allele frequency- G:0.05WA NA EA 358
    rs31809631,2
    C--32080275(-) CCACTC/GCTATC 1 -- ut31 ese30--------

    HapMap Linkage Disequilibrium report for NOTCH4 (32162620 - 32191844 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for NOTCH4:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2677748CNV Deletion23128226
    dgv6643n71CNV Loss21882294
    nsv884712CNV Loss21882294
    dgv6645n71CNV Loss21882294
    nsv830629CNV Loss17160897
    nsv10826CNV Loss18304495
    dgv6644n71CNV Loss21882294
    nsv884715CNV Loss21882294
    nsv462877CNV Loss19166990
    dgv1929e1CNV Complex17122850


    Human Gene Mutation Database (HGMD): NOTCH4
    SABiosciences Cancer Mutation PCR Assays
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    Pancreatic Cancer
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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: 164951    OMIM disorders: --

    20/55 diseases for NOTCH4 (see all 55):    About MalaCards
    pseudobulbar palsy    schizoaffective disorder    tongue cancer    cadasil
    klippel-trenaunay syndrome    schizophrenia    arteriovenous malformation    alopecia areata
    arterial occlusive disease    cerebrovascular accident    narcolepsy    vascular dementia
    plasmacytoma    alopecia    hepatitis    arteriosclerosis
    kawasaki disease    inclusion body myositis    mood disorder    hemangioma

    5 diseases from the University of Copenhagen DISEASES database for NOTCH4:
    Cadasil     Migraine     Vascular dementia     Cerebrovascular accident
    Pseudobulbar palsy

    NOTCH4 for disorders           About GeneDecksing


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

    10/14 Novoseek inferred disease relationships for NOTCH4 gene (see all 14)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    schizophrenia 54.1 83 12873802 (6), 12627456 (5), 16894623 (5), 11407996 (5) (see all 26)
    mammary tumor 39.3 3 9243759 (1), 15288259 (1)
    schizoaffective disorder 24.8 4 11239712 (4)
    tumors 18.5 42 18339869 (3), 9243759 (3), 16778208 (3), 17675579 (2) (see all 18)
    hepatocellular carcinoma 16.5 8 16951162 (2), 17696940 (1), 17920003 (1), 19304334 (1)
    breast cancer 16.1 5 17158237 (2), 18339869 (2)
    cancer 15 6 18184405 (2), 17158237 (1), 15867348 (1), 17804716 (1)
    ovarian cancer 11.1 11 18974129 (2), 18632624 (2), 16778208 (1)
    leukemia 0 1 9461376 (1)
    carcinoma squamous cell 0 1 20359736 (1)

    Genetic Association Database (GAD): NOTCH4
    Human Genome Epidemiology (HuGE) Navigator: NOTCH4 (42 documents)
    Tumor Gene Database (TGDB): NOTCH4

    Export disorders for NOTCH4 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 NOTCH4 gene, integrated from 9 sources (see all 210):
    (articles sorted by number of sources associating them with NOTCH4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Gene organization of human NOTCH4 and (CTG)n polymorphism in this human counterpart gene of mouse proto-oncogene Int3. (PubMed id 9168133)1, 2, 9 Sugaya K.... Mita K. (1997)
    2. A review and re-evaluation of an association between the NOTCH4 locus and schizophrenia. (PubMed id 16894623)1, 4, 9 Wang Z....Shen Y. (2006)
    3. Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families. (PubMed id 17054719)1, 4, 9 Liu C.M....Hwu H.G. (2007)
    4. No evidence for association between NOTCH4 and schizophrenia in a large family-based and case-control association analysis. (PubMed id 16969274)1, 4, 9 Ivo R....Cichon S. (2006)
    5. Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples. (PubMed id 12873802)1, 4, 9 Takahashi S....Tsuang M.T. (2003)
    6. NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder. (PubMed id 11239712)1, 4, 9 Ujike H....Kuroda S. (2001)
    7. A NOTCH4 association with multiple sclerosis is secondary to HLA-DR*1501. (PubMed id 14651518)1, 4, 9 Duvefelt K....Hillert J. (2004)
    8. NOTCH4 gene haplotype is associated with schizophrenia in African Americans. (PubMed id 14732589)1, 4, 9 Luo X....Gelernter J. (2004)
    9. NOTCH4 and the frontal lobe in schizophrenia. (PubMed id 12627456)1, 4, 9 Wassink T.H....Andreasen N.C. (2003)
    10. Two NOTCH4 polymorphisms and their relation to schizophrenia susceptibility and different personality traits. (PubMed id 12605097)1, 4, 9 Carmine A....Olson L. (2003)

    (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: 4855 HGNC: 7884 AceView: NOTCH4 Ensembl:ENSG00000204301 euGenes: HUgn4855
    ECgene: NOTCH4 Kegg: 4855 H-InvDB: NOTCH4

    (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 NOTCH4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOTCH4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for NOTCH4 gene:
    Search GeneIP for patents involving NOTCH4

    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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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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