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Aliases for NOTCH2 Gene

Aliases for NOTCH2 Gene

  • Notch 2 2 3 4 5
  • HN2 3 4
  • Neurogenic Locus Notch Homolog Protein 2 3
  • Notch (Drosophila) Homolog 2 2
  • Notch Homolog 2 (Drosophila) 2
  • Notch Homolog 2 3
  • HJCYS 3
  • AGS2 3

External Ids for NOTCH2 Gene

Previous GeneCards Identifiers for NOTCH2 Gene

  • GC01M120900
  • GC01M119292
  • GC01M119601
  • GC01M119800
  • GC01M120100
  • GC01M120256
  • GC01M120454
  • GC01M118312

Summaries for NOTCH2 Gene

Entrez Gene Summary for NOTCH2 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

GeneCards Summary for NOTCH2 Gene

NOTCH2 (Notch 2) is a Protein Coding gene. Diseases associated with NOTCH2 include Alagille Syndrome 2 and Hajdu-Cheney Syndrome. Among its related pathways are Gene Expression and Notch signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include calcium ion binding and transcription factor activity, ligand-activated RNA polymerase II transcription factor binding. An important paralog of this gene is NOTCH1.

UniProtKB/Swiss-Prot for NOTCH2 Gene

  • 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). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737).

Gene Wiki entry for NOTCH2 Gene

Additional gene information for NOTCH2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOTCH2 Gene

Genomics for NOTCH2 Gene

GeneHancer (GH) Regulatory Elements for NOTCH2 Gene

Promoters and enhancers for NOTCH2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J120067 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 650.7 +0.7 702 2.4 ARID4B SIN3A GLI4 ZNF2 YY1 GLIS2 ZNF213 ELK1 ZNF143 KLF7 NOTCH2 LOC101929178 GC01P119934
GH01J120098 Promoter/Enhancer 1 EPDnew Ensembl dbSUPER 650.3 -30.3 -30298 3.2 KLF1 LOC105378939 NOTCH2 LOC101929178
GH01J119985 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 12.6 +82.4 82351 3.8 JUN RAD21 RFX5 ZNF664 POLR2A RCOR1 FOSL2 FOS RUNX3 CEBPB NOTCH2 ADAM30 ZNF697 ENSG00000261662 GC01P119934
GH01J120088 Enhancer 1.1 FANTOM5 Ensembl ENCODE dbSUPER 8.1 -18.6 -18592 0.6 ZNF146 FOS ZNF600 NOTCH2 ZNF697 FCGR1B LOC105378939 LOC101929178
GH01J120141 Enhancer 1.1 FANTOM5 Ensembl ENCODE dbSUPER 7.3 -74.0 -73998 3.8 IKZF1 MLLT1 DPF2 IKZF2 SPI1 ZNF507 ZNF697 NOTCH2 GC01P120130 SEC22B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NOTCH2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NOTCH2 gene promoter:
  • Nkx6-1
  • C/EBPalpha
  • IRF-1
  • MEF-2A
  • aMEF-2
  • AML1a
  • Elk-1
  • Tal-1beta
  • ITF-2

Genomic Locations for NOTCH2 Gene

Genomic Locations for NOTCH2 Gene
158,151 bases
Minus strand
158,142 bases
Minus strand

Genomic View for NOTCH2 Gene

Genes around NOTCH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NOTCH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NOTCH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NOTCH2 Gene

Proteins for NOTCH2 Gene

  • Protein details for NOTCH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Neurogenic locus notch homolog protein 2
    Protein Accession:
    Secondary Accessions:
    • Q5T3X7
    • Q99734
    • Q9H240

    Protein attributes for NOTCH2 Gene

    2471 amino acids
    Molecular mass:
    265405 Da
    Quaternary structure:
    • Heterodimer of a C-terminal fragment N(TM) and an 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 NOTCH2. Interacts with RELA/p65 (By similarity). Interacts with HIF1AN. Interacts (via ANK repeats) with TCIM, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (PubMed:25985737). Interacts with CUL1, RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase complex components (PubMed:29149593).

    Three dimensional structures from OCA and Proteopedia for NOTCH2 Gene

neXtProt entry for NOTCH2 Gene

Post-translational modifications for NOTCH2 Gene

  • 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).
  • Hydroxylated by HIF1AN.
  • Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.
  • Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway.
  • Glycosylation at Asn1465, isoforms=1102, isoforms=733, isoforms=613, isoforms=155, and isoforms=46
  • Ubiquitination at isoforms=1705
  • Modification sites at PhosphoSitePlus

Other Protein References for NOTCH2 Gene

No data available for DME Specific Peptides for NOTCH2 Gene

Domains & Families for NOTCH2 Gene

Gene Families for NOTCH2 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for NOTCH2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the NOTCH family.
  • Belongs to the NOTCH family.
genes like me logo Genes that share domains with NOTCH2: view

Function for NOTCH2 Gene

Molecular function for NOTCH2 Gene

UniProtKB/Swiss-Prot 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). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737).
GENATLAS Biochemistry:
Drosophila Notch homolog 2,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 neoplasia associated translocations

LifeMap Function Summary for NOTCH2 Gene

During embryonic development, NOTCH2 as signaling molecule is secreted from the following cells

Phenotypes From GWAS Catalog for NOTCH2 Gene

Gene Ontology (GO) - Molecular Function for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 10079256
GO:0038023 signaling receptor activity NAS 9244302
GO:0038049 transcription factor activity, ligand-activated RNA polymerase II transcription factor binding TAS 9244302
genes like me logo Genes that share ontologies with NOTCH2: view
genes like me logo Genes that share phenotypes with NOTCH2: view

Human Phenotype Ontology for NOTCH2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NOTCH2 Gene

MGI Knock Outs for NOTCH2:

Animal Model Products

  • Taconic Biosciences Mouse Models for NOTCH2

miRNA for NOTCH2 Gene

miRTarBase miRNAs that target NOTCH2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NOTCH2 Gene

Localization for NOTCH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NOTCH2 Gene

Notch 2 extracellular truncation: Cell membrane; Single-pass type I membrane protein.
Notch 2 intracellular domain: Nucleus. Cytoplasm. Note=Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM (PubMed:25985737). {ECO:0000269 PubMed:25985737}.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NOTCH2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 5
endoplasmic reticulum 5
golgi apparatus 5
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005576 extracellular region TAS --
GO:0005634 nucleus IDA,IEA 1303260
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with NOTCH2: view

Pathways & Interactions for NOTCH2 Gene

genes like me logo Genes that share pathways with NOTCH2: view

SIGNOR curated interactions for NOTCH2 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001709 cell fate determination TAS 9244302
GO:0002315 marginal zone B cell differentiation ISS --
GO:0003184 pulmonary valve morphogenesis IMP 16773578
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated TAS 9244302
genes like me logo Genes that share ontologies with NOTCH2: view

Drugs & Compounds for NOTCH2 Gene

(10) Drugs for NOTCH2 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
PF-03084014 Pharma other γ-secretase inhibitor, Other 0
BMS-983970 Pharma 0
FLI-06 Pharma 0
LY3039478 Pharma Notch inhibitor, novel and potent 0
LY-900009 Pharma Potent Notch inhibitor 0
genes like me logo Genes that share compounds with NOTCH2: view

Transcripts for NOTCH2 Gene

mRNA/cDNA for NOTCH2 Gene

(2) REFSEQ mRNAs :
(9) Additional mRNA sequences :
(379) Selected AceView cDNA sequences:
(8) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NOTCH2 Gene

Notch 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH2 Gene

No ASD Table

Relevant External Links for NOTCH2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for NOTCH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NOTCH2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NOTCH2 Gene

This gene is overexpressed in Adrenal (32.5) and Bone (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NOTCH2 Gene

Protein tissue co-expression partners for NOTCH2 Gene

NURSA nuclear receptor signaling pathways regulating expression of NOTCH2 Gene:


SOURCE GeneReport for Unigene cluster for NOTCH2 Gene:


mRNA Expression by UniProt/SwissProt for NOTCH2 Gene:

Tissue specificity: Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed in the embryo.

Evidence on tissue expression from TISSUES for NOTCH2 Gene

  • Nervous system(4.8)
  • Blood(4.6)
  • Lung(3.5)
  • Skin(2.8)
  • Liver(2.7)
  • Intestine(2.4)
  • Spleen(2.4)
  • Kidney(2.3)
  • Heart(2.2)
  • Bone marrow(2.1)
  • Lymph node(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NOTCH2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cheek
  • chin
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • meninges
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • sinus
  • skull
  • tooth
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • abdominal wall
  • biliary tract
  • gallbladder
  • intestine
  • kidney
  • liver
  • pancreas
  • pelvis
  • penis
  • testicle
  • ureter
  • urethra
  • urinary bladder
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
  • blood
  • blood vessel
  • hair
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with NOTCH2: view

No data available for mRNA differential expression in normal tissues for NOTCH2 Gene

Orthologs for NOTCH2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NOTCH2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia NOTCH2 33
  • 99.76 (n)
(Canis familiaris)
Mammalia NOTCH2 34 33
  • 91.83 (n)
(Bos Taurus)
Mammalia NOTCH2 34 33
  • 91 (n)
(Mus musculus)
Mammalia Notch2 16 34 33
  • 87.14 (n)
(Monodelphis domestica)
Mammalia NOTCH2 34
  • 87 (a)
(Rattus norvegicus)
Mammalia Notch2 33
  • 86.84 (n)
(Ornithorhynchus anatinus)
Mammalia NOTCH2 34
  • 80 (a)
(Gallus gallus)
Aves NOTCH2 34 33
  • 74.1 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486344 33
  • 68.89 (n)
(Danio rerio)
Actinopterygii notch2 34 33
  • 61.03 (n)
fruit fly
(Drosophila melanogaster)
Insecta N 34 35
  • 42 (a)
CG15388 35
  • 39 (a)
SP1070 35
  • 38 (a)
(Caenorhabditis elegans)
Secernentea W02C12.1 35
  • 38 (a)
Y69H2.12 35
  • 30 (a)
F55G1.13 35
  • 29 (a)
Y69H2.11 35
  • 28 (a)
Y69H2.2 35
  • 28 (a)
F55H12.3 35
  • 27 (a)
R05G6.9 35
  • 26 (a)
mup-4 35
  • 25 (a)
lin-12 35
  • 25 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SWI6 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 41 (a)
Species where no ortholog for NOTCH2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NOTCH2 Gene

Gene Tree for NOTCH2 (if available)
Gene Tree for NOTCH2 (if available)
Evolutionary constrained regions (ECRs) for NOTCH2: view image

Paralogs for NOTCH2 Gene

Paralogs for NOTCH2 Gene

(15) SIMAP similar genes for NOTCH2 Gene using alignment to 4 proteins:

  • Q6IQ50_HUMAN
  • R4GN02_HUMAN Pseudogenes for NOTCH2 Gene

genes like me logo Genes that share paralogs with NOTCH2: view

Variants for NOTCH2 Gene

Sequence variations from dbSNP and Humsavar for NOTCH2 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs111033632 pathogenic, Alagille syndrome 2, Alagille syndrome 2 (ALGS2) [MIM:610205] 119,967,555(-) C/T coding_sequence_variant, missense_variant
rs115325955 benign, not specified, Hajdu-Cheney syndrome 119,937,285(-) G/A coding_sequence_variant, synonymous_variant
rs116321057 uncertain-significance, not specified, Hajdu-Cheney syndrome 119,922,741(-) C/T coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
rs142876168 benign, Hajdu-Cheney syndrome 119,937,325(-) T/C coding_sequence_variant, missense_variant
rs143236410 benign, likely-benign, not specified, Hajdu-Cheney syndrome 119,916,628(-) G/T coding_sequence_variant, genic_downstream_transcript_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for NOTCH2 Gene

Variant ID Type Subtype PubMed ID
dgv151n106 CNV deletion 24896259
dgv152n106 CNV duplication 24896259
dgv166e59 CNV duplication 20981092
dgv167e59 CNV duplication 20981092
dgv168e59 CNV duplication 20981092
esv22009 CNV gain+loss 19812545
esv3329918 CNV duplication 20981092
esv3568231 CNV gain 25503493
esv3578135 CNV loss 25503493
nsv10683 CNV gain 18304495
nsv1075781 CNV duplication 25765185
nsv1115350 CNV duplication 24896259
nsv1118437 CNV duplication 24896259
nsv1128598 CNV duplication 24896259
nsv1139488 CNV duplication 24896259
nsv1148798 CNV duplication 26484159
nsv1148976 CNV duplication 26484159
nsv1150110 CNV duplication 26484159
nsv1152523 CNV duplication 26484159
nsv2610 CNV deletion 18451855
nsv428201 CNV gain 18775914
nsv436325 CNV deletion 17901297
nsv514912 CNV gain 21397061
nsv524681 CNV gain 19592680
nsv547625 CNV loss 21841781
nsv820378 CNV duplication 20802225
nsv824331 CNV gain 20364138
nsv831226 CNV gain+loss 17160897
nsv946188 CNV duplication 23825009
nsv951405 CNV duplication 24416366
nsv955084 CNV deletion 24416366

Variation tolerance for NOTCH2 Gene

Residual Variation Intolerance Score: 1.87% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.41; 63.75% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NOTCH2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NOTCH2 Gene

Disorders for NOTCH2 Gene

MalaCards: The human disease database

(16) MalaCards diseases for NOTCH2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alagille syndrome 2
  • algs
hajdu-cheney syndrome
  • hjcys
splenic marginal zone lymphoma
  • smzl
lacrimal gland adenoid cystic carcinoma
  • adenoid cystic carcinoma of lacrimal gland
alagille syndrome 1
  • algs1
- elite association - COSMIC cancer census association via MalaCards


  • Alagille syndrome 2 (ALGS2) [MIM:610205]: A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. {ECO:0000269 PubMed:16773578}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Hajdu-Cheney syndrome (HJCYS) [MIM:102500]: A rare, autosomal dominant skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes. {ECO:0000269 PubMed:21378985, ECO:0000269 PubMed:21378989, ECO:0000269 PubMed:21681853, ECO:0000269 PubMed:21712856, ECO:0000269 PubMed:21793104, ECO:0000269 PubMed:23389697, ECO:0000269 PubMed:29149593}. Note=The disease is caused by mutations affecting the gene represented in this entry. NOTCH2 nonsense and frameshift mutations associated with Hajdu-Cheney syndrome cluster to the last coding exon of the gene. Mutant mRNA products escape nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner (PubMed:21378989). The pathological mechanism at cellular level involves disruption of a high affinity degron recognized by FBXW7 at the C-terminus, loss of interaction with FBXW7, reduced ubiquitination and degradation, and increased NOTCH2 levels. Bone marrow cells derived from HJCYS patients have an enhanced capacity of osteoclastogenesis due to sustained NOTCH2 activity (PubMed:29149593). {ECO:0000269 PubMed:21378989, ECO:0000269 PubMed:29149593}.

Additional Disease Information for NOTCH2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NOTCH2: view

No data available for Genatlas for NOTCH2 Gene

Publications for NOTCH2 Gene

  1. Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects. (PMID: 16899352) Passos Gregorio S … Dias-Neto E (Schizophrenia research 2006) 3 22 44 58
  2. NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis. (PMID: 29149593) Fukushima H … Inuzuka H (Molecular cell 2017) 3 4 58
  3. C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling. (PMID: 25985737) Zhu P … Fan Z (Nature communications 2015) 3 4 58
  4. Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome. (PMID: 23389697) Zhao W … Mannstadt M (Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2013) 3 4 58
  5. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. (PMID: 21378985) Simpson MA … Trembath RC (Nature genetics 2011) 3 4 58

Products for NOTCH2 Gene

Sources for NOTCH2 Gene

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