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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)
 Explore 55 diseases affiliated with
NOTCH4 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for NOTCH4    

Aliases
for NOTCH4 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
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     HNotch41

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


Summaries
for NOTCH4 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 NOTCH4:
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)

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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000006.11  NC_018917.1  NT_007592.15  NT_113891.2  NT_167244.1  NT_167246.1  NT_167247.1  NT_167248.1  
NT_167249.1  
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-,ALT_REF_LOCI_2 32,111,094-32,179,504      Chr6-,ALT_REF_LOCI_4 32,125,100-32,154,348      Chr6-,ALT_REF_LOCI_5 32,153,867-32,183,114     
Chr6-,ALT_REF_LOCI_6 32,120,241-32,185,049      Chr6-,ALT_REF_LOCI_1 32,173,961-32,191,827      Chr6-,ALT_REF_LOCI_7 32,099,811-32,129,038     

Proteins
for NOTCH4 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: 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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q99466

    • NOTCH4 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_004548.3  
    ENSEMBL proteins: 
     ENSP00000364163   ENSP00000398123  
    Reactome Protein details: Q99466
    Human Recombinant Protein Products: 
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    OriGene Protein Over-expression Lysate: NOTCH4
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    GenScript Custom Purified and Recombinant Proteins Services for NOTCH4
    Novus Biologicals NOTCH4 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for NOTCH4

    Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9):    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
    Search for Antibodies for NOTCH4 at Abcam  
    Uscn Antibodies for NOTCH4
    ThermoFisher Antibodies for NOTCH4

    Assay Products for NOTCH4: 
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    GenScript Custom Assay Services for NOTCH4
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    Uscn ELISAs and CLIAs for NOTCH4

    Protein Domains /
    Families
    for NOTCH4 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    NOTCH4 for domains           About GeneDecksing

    5/11 InterPro domains/families (see all 11):
     IPR001881 EGF-like_Ca-bd
     IPR008297 Notch
     IPR000742 EG-like_dom
     IPR000800 Notch_dom
     IPR013032 EGF-like_CS

    Graphical View of Domain Structure for InterPro Entry Q99466

    ProtoNet protein and cluster: Q99466

    4 Blocks protein families:
    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


    Function
    for NOTCH4 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: 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

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

    OriGene 3'-UTR Clone: NOTCH4
    Browse MicroRNA Expression Plasmids
    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 plasmid: NOTCH4 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NOTCH4 (see all 7)
    OriGene shRNA RFP: NOTCH4
    OriGene siRNA: NOTCH4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOTCH4

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for NOTCH4

    Clone
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    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for NOTCH4 (see all 3)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for NOTCH4
    OriGene custom cloning services – gene synthesis, subcloning, mutagenesis, variant library, vector shuttling 
    GenScript: all cDNA clones in your preferred vector: NOTCH4 (NM_004557)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOTCH4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOTCH4 

    Cell Line
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    Search LifeMap BioReagents cell lines for NOTCH4

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH4

    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


    Animal Models:
         Mouse knock-out Notch4tm1Grid for NOTCH4
         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


    Pathways & Interactions
    for NOTCH4 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 - 5/20 super-pathways (see all 20) 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

    1 EMD Millipore Pathway for NOTCH4
        Selected targets of GCR-alpha

    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 
        Neural Crest Differentiation
    Notch Signaling Pathway
    Delta-Notch Signaling Pathway
    Notch signaling pathway

    5/17        Reactome Pathways for NOTCH4 (see all 17)
        Pre-NOTCH Expression and Processing
    A third proteolytic cleavage releases NICD
    Notch-HLH transcription pathway
    NOTCH4 mRNA translation controlled by miRNAs
    Signaling by NOTCH4


    2         Kegg Pathways  (Kegg details for NOTCH4):
        Dorso-ventral axis formation
    Notch signaling pathway


    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)

    5/18 Interacting proteins for NOTCH4 (Q994662, 3 ENSP000003641634) via UniProtKB, MINT, STRING, and/or I2D (see all 18)
    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): 5/17 biological process terms (GO ID links to tree view) (see all 17):    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



    Drugs & Compounds
    for NOTCH4 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

    NOTCH4 for compounds           About GeneDecksing

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

    Browse Tocris compounds for NOTCH4
    2 Novoseek 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 

    Transcripts
    for NOTCH4 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 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

    miRNA
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    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 plasmid: NOTCH4 3' UTR sequence
    Inhib. RNA
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    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NOTCH4 (see all 7)
    OriGene shRNA RFP: NOTCH4
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    Clone
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    Primer
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat NOTCH4
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NOTCH4

    Additional cDNA 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):

    AI880212 BP368231 CA430677 AI300614 CD672916 AI355714 CK821917 BU682631 
    AL705928 BM811035 AJ705578 AI093309 BC018724 BQ711693 BE858452 BQ011648 
    AA868548 BM705319 AJ243937 BQ447238 BQ183096 BU172121 NM_022107 BQ053714 

    GeneLoc Exon Structure


    Expression
    for NOTCH4 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

    NOTCH4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GTAGGGAGGA

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

    NOTCH4 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    4 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Lateral Plate MesodermEmbryonic Blood IslandsAngioblastsEndothelium
    Lateral Plate MesodermEmbryonic Capillary PlexusAngioblastsEndothelium
    Lateral Plate MesodermProepicardiumAngioblastsEndothelium
    PlacentaExtravillous Cytotrophoblast LayerExtravillous Cytotrophoblast CellsExtraembryonic Tissues, Placenta
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    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

    Primer
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    Orthologs
    for NOTCH4 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 NOTCH4 gene from 3/15 species (see all 15)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    lizard
    (Anolis carolinensis)    		 Reptilia NOTCH46
    CRB26
    		 --
    		 28(a)
    22(a)
    		 possible ortholog
    possible ortholog
    		 2(198817538-198859587)
    GL344112.1(574-12270)
    fruit fly
    (Drosophila melanogaster)    		 Insecta CG153883   -- 39(a)
    (best of 2)    		   22E1   --
    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
    for NOTCH4 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for NOTCH4 gene
    SNED12  NOTCH12  NOTCH32  DLL32  DLL42  JAG22  CRB22  NOTCH22  
    JAG12  DNER2  CRB12  DLL12  
    9 SIMAP similar genes for NOTCH4 using alignment to 7 protein entries:     NOTC4_HUMAN (see all proteins):
    F9    DKFZp761E1322    MTPN    NOTCH2    CRB1    DLK1
    CDKN2A    CRB2    NOTCH2NL

    NOTCH4 for paralogs           About GeneDecksing



    Genomic Variants
    for NOTCH4 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

    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)


    10/737 NCBI SNPs in NOTCH4 are shown (see all 737)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 6 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs31809631,2
    		C--31916874(-) CCACTC/GCTATC 1 -- ut31 ese30--------
    rs728463051,2
    		C,--31916889(+) AAGAAA/GCGCTT 1 -- ut310--------
    rs412704681,2
    		--31917258(+) GAAGAC/TGTCTG 1 -- ut310--------
    rs81925831,2
    		C,F,H,--31917469(-) CTTGAC/TTGTGG 2 D syn1 ese321Minor allele frequency- T:0.05NS EA WA NA EU 8491
    rs10445071,2
    		C,F,--31917736(-) TATTCT/GCATTG 2 /S syn1 ese35Minor allele frequency- G:0.04MN NS NA WA EU 514
    rs81925811,2
    		C,--31917859(-) CATGGG/AGGCGG 2 /G syn1 ese32Minor allele frequency- A:0.02NS EA 198
    rs132155671,2
    		C,H--31917943(+) CGGGCC/TTCTGG 2 E syn1 ese34Minor allele frequency- T:0.00NS EA 412
    rs81925801,2
    		C,H--31917973(-) CTGCTG/TACGCT 2 L syn1 ese34Minor allele frequency- T:0.00NS EA 420
    rs81925791,2
    		C,F,H,--31917994(-) CACCAA/GCGTAA 2 Q syn1 ese317Minor allele frequency- G:0.07NS EA NA WA EU 1951
    rs81925781,2
    		C,H--31918257(-) TCAGGC/GGCACG 1 -- int15Minor allele frequency- G:0.00NS EA EU 1013

    HapMap Linkage Disequilibrium report for NOTCH4 (32162620 - 32191844 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 2 variations for NOTCH4
         2 CNVs: 3602 32787
    Human Gene Mutation Database (HGMD): NOTCH4

    SABiosciences Cancer Mutation PCR Assays
    1 SABiosciences qBiomarker Copy Number PCR Array containing NOTCH4:
    Pancreatic Cancer
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    DNA2.0 Custom Variant and Variant Library Synthesis for NOTCH4

    Disorders / Diseases
    for NOTCH4 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
    NOTCH4 for disorders           About GeneDecksing

    OMIM gene information: 164951    OMIM disorders: --

    20/55 diseases for NOTCH4 (see all 55):    About MalaCards
    klippel-trenaunay syndrome    schizophrenia    hepatitis    pseudobulbar palsy
    schizoaffective disorder    alopecia areata    arteriovenous malformation    arterial occlusive disease
    cerebrovascular accident    systemic lupus erythematosus    lupus erythematosus    cadasil
    rheumatoid arthritis    hematuria    alopecia    epithelial ovarian cancer
    mood disorder    tongue cancer    ulcerative colitis    ovarian cancer

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

    10/14 Novoseek 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

    Publications
    for NOTCH4 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 NOTCH4 gene, integrated from 9 sources (see all 192):
    (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. 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)
    3. NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder. (PubMed id 11239712)1, 4, 9 Ujike H....Kuroda S. (2001)
    4. A NOTCH4 association with multiple sclerosis is secondary to HLA-DR*1501. (PubMed id 14651518)1, 4, 9 Duvefelt K....Hillert J. (2004)
    5. NOTCH4 gene haplotype is associated with schizophrenia in African Americans. (PubMed id 14732589)1, 4, 9 Luo X....Gelernter J. (2004)
    6. NOTCH4 and the frontal lobe in schizophrenia. (PubMed id 12627456)1, 4, 9 Wassink T.H....Andreasen N.C. (2003)
    7. Two NOTCH4 polymorphisms and their relation to schizophrenia susceptibility and different personality traits. (PubMed id 12605097)1, 4, 9 Carmine A....Olson L. (2003)
    8. The (CTG)n polymorphism in the NOTCH4 gene is not associated with schizophrenia in Japanese individuals. (PubMed id 11407996)1, 4, 9 Imai K....Suzuki T. (2001)
    9. Five NOTCH4 polymorphisms show weak evidence for association with schizophrenia: evidence from meta-analyses. (PubMed id 15653273)1, 4, 9 Glatt S.J....Faraone S.V. (2005)
    10. [Association study of NOTCH4 gene polymorphisms with schizophrenia and mood disorders in mixed pedigrees] (PubMed id 16378929)1, 4, 9 Wang Z.W....Jing S.D. (2005)

    External Searches for NOTCH4 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 NOTCH4 gene

    (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

    Other Databases showing NOTCH4 gene

    (According to HUGE)
    About This Section
    		   --

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

    Intellectual Property
    for NOTCH4 gene

    (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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