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Symbol NOTCH2 contributors: mct/shn - updated : 13-09-2017
HGNC name notch 2
HGNC id 7882
Corresponding disease
ALGS2 Alagille syndrome 2
HJCYS Hajdu-Cheney syndrome
Location 1p11.2      Physical location : 120.454.177 - 120.612.276
Synonym name
  • Notch (Drosophila) homolog 2
  • Notch homolog 2 (Drosophila)
  • Notch homolog 2
  • neurogenic locus notch homolog protein 2
  • Synonym symbol(s) hN2, AGS2, HJCYS
    TYPE functioning gene
    STRUCTURE 158.10 kb     34 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Map pter - D1S185 - D1S514 - NOTCH2 - cen
    Physical map
    LOC343495 1p11.2 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140) HAO2 1p13.3-p13.2 hydroxyacid oxidase 2 (long chain) HSD3B2 1p13.1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 LOC391073 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC391074 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) LOC391075 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC391076 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) LOC391077 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) HSD3B1 1p13.1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 LOC391078 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC391079 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) LOC128102 1p11.2 3-beta-hydroxysteroid dehydrogenase, tissue-type heart LOC391080 1 similar to glyceraldehyde 3-phosphate dehydrogenase LOC391081 1 similar to 3 BETA-HYDROXYSTEROID DEHYDROGENASE/DELTA 5-->4-ISOMERASE (3BETA-HSD) MGC45731 1p11.2 hypothetical protein MGC45731 PHGDH 1p12 phosphoglycerate dehydrogenase HMGCS2 1p12 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial) REG4 1q12-q21 regenerating islet-derived family, member 4 LOC343505 1p11.2 similar to dJ1182A14.5.1 (novel gene (isoform 1)) LOC391082 1 similar to Profilin I ADAM30 1p12-p11 a disintegrin and metalloproteinase domain 30 NOTCH2 1p12-p11 Notch homolog 2 (Drosophila)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    34 splicing 11474 - 2471 - 1997 9032325
    22 splicing 4326 - 1235 - 1997 9032325
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly Homo sapiens
    Endocrinepancreas   highly
     thyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    Reproductivefemale systembreastmammary gland highly
     male systemtestis  highly
    Urinarykidney   highly
    Visualeyeanterior segmentcornea highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Muscularsmoothvessel predominantly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Visualepithelial cell
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period embryo
    Text atrioventricular cord
  • a signal peptide
  • 36 extracellular EGF repeats
  • three notch/lin-12 (LNR) repeats
  • two PEST sequences
  • six cdc10/ankyrin (ANK) repeats
  • a RAM23 domain
  • C terminus of the intracellular domain contains a PEST sequence known to mediate proteosomal destruction of the protein
  • mono polymer heteromer , dimer
    isoforms Precursor
    interspecies ortholog to NOTCH2, Pan troglodytes
    ortholog to notch2, danio rerio
    homolog to Notch2, Rattus norvegicus
    ortholog to Notch2, Mus musculus
  • NOTCH family
  • CATEGORY regulatory , protooncogene , receptor
        plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • receptor for membrane-bound ligands Jagged1, Jagged2, Delta-like1, Delta-like3 and Delta-like4
  • an important element in dental physiological and pathogenic conditions (
  • mediating cell-cell interactions that specify cell fate during development
  • as other Notch family members and ligands, expressed in the human corneal epithelium and appear to play pivotal roles in corneal epithelial cell differentiation
  • central regulator of pancreatic intraepithelial neoplasia progression and malignant transformation
  • essential role of NOTCH2 and MYC in the initiation of a neoplastic transformation program in pancreatic cells
  • play a role in the regulation of red cell differentiation (
  • important role for NOTCH2 signaling in bone homeostasis
  • importance of NOTCH2 in the development and maintenance of the skeleton, and modulate RANKL-induced osteoclastogenesis
  • NOTCH2 and NOTCH3 act together to govern vascular development and smooth muscle differentiation
  • Notch signaling through the NOTCH2 receptor is essential for normal biliary tubulogenesis during liver development
  • NOTCH1 and NOTCH2 expression in osteoblast precursors regulates cancellous bone volume and microarchitecture
  • canonical, NOTCH2-dependent signaling plays likely a role in human decidualization
  • NOTCH2 signalling, activated by cell-cell contact of neighbouring distal cell column trophoblasts (dCCTs), could attenuate trophoblast migration
  • NOTCH1 is the primary receptor regulating intestinal stem cell function and NOTCH1 and NOTCH2 together regulate epithelial cell proliferation, cell fate determination, and post-injury regeneration
  • discrete roles for NOTCH2 and NOTCH3 in VSMCs and these roles are linked to specific upstream regulators that control their expression
  • NOTCH2 and NOTCH3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the ductus arteriosus
  • NOTCH2 and NOTCH3 inhibited both cell proliferation and cell apoptosis trophoblast cell lines
  • NOTCH1 and NOTCH2 are the primary NOTCH receptors regulating epithelial cell homoeostasis in human stomach
  • physiologically regulates bone remodeling by inhibiting trabecular bone formation in the appendicular skeleton
  • NOTCH2 signaling is linked to MYC expression and plays a key role in the regulation of Mesenchymal stem/stromal cells (MSCs) proliferation
  • CELLULAR PROCESS cell cycle
    cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    cell communication
    signaling signal transduction
    Notch2 signaling is required for potent antitumor immunity
    a component
  • protein constituent of plasma membrane
    small molecule
  • CBF1 (
  • Delta1, Jagged1, and Jagged2 as ligands for Notch2
  • mastermind-like 1 (Drosophila), MAML1
  • glycogen synthase kinase-3 beta, GSK-3 beta
  • TAT
  • NOTCH1 in concert with NOTCH2 contributes to the morphogenesis of renal vesicles into S-shaped bodies in a RBPJ-dependent manner
  • directly controls FOS transcription associated with Marginal zone B (MZB) cells development 5)
  • clear interaction between NOTCH2 and FOS, but the exact role of FOS in forming MZB cells has yet to be determined 5)
  • both NOTCH2 and NOTCH3 can promote SDC2 expression in smooth muscle cells
  • potential novel roles of NUMB/NUMBL in regulating heart trabeculation and compaction by inhibiting NOTCH2 and BMP10 signalling
  • receptor-specific function for NOTCH2 in mediating vascular smooth muscle cell growth arrest through CDKN1B
  • NOTCH2 inhibits PDGFB-dependent proliferation and its expression is decreased by PDGFB
  • C8orf4 negatively regulates the self-renewal of liver cancer stem cells (CSCs)via suppression of NOTCH2 signalling
  • JAG1 and NOTCH2 play a key role in kidney fibrosis development by regulating TFAM expression and metabolic reprogramming
  • cell & other
    activated by delta (DLK1) jagged (JAG*)
    in response to TNF (TNF signaling activates NOTCH2 that sensitizes endothelial cells to apoptosis via modulation of the key apoptosis regulator survivin
    induced by MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2
    Other 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
    modulated by FRINGE (LFNG,MFNG,RFNG) through elongation of linked fucose residues on side chains on some EGF repeats
    corresponding disease(s) ALGS2 , HJCYS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    with FCER2 in B-cell chronic lymphocytic leukemia
    tumoral   translocation    
    in neoplasia
    constitutional somatic mutation      
  • AGS is a disorder caused by mutations in JAG1 or NOTCH2
  • the vast majority of patients with AGS have mutations in JAG1, with only a small subset showing NOTCH2 mutations
  • tumoral     --over  
    correlated closely with colorectal cancer and may play a role in tumor inhibition in colon carcinogenesis
    constitutional     --low  
    in immune thrombocytopenic purpura
    tumoral germinal mutation     gain of function
    in the pathogenesis of a subset of B-cell lymphoma
    tumoral     --over  
    in human hepatocellular carcinoma (HCC) tissues
    tumoral       gain of function
    in liver cancer stem cells (CSCs)
    Variant & Polymorphism
    Candidate gene
    Therapy target
    ablation of NOTCH2 but not NOTCH1 leads to an abrogation of pancreatic intraepithelial neoplasia progression, and increased survival
    Notch pathway is a potential target for therapeutic intervention in osteoporosis
    as a potential therapeutic target for hepatocellular carcinoma
  • Mice homozygous for the Notch2(del1) mutation died perinatally from defects in glomerular development in the kidney while mice heterozygous for both the Notch2(del1) and Jag1(dDSL) mutations exhibit a less severe glomerular defect (
  • mice double mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry (
  • when Notch2 and Notch3 genes are simultaneously disrupted, mice die in utero at mid-gestation due to severe vascular abnormalities
  • mice harboring Notch2 mutations analogous to those in Hajdu-Cheney syndrome (HCS) (Notch2HCS) are severely osteopenic because of enhanced bone resorption