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 process... See more...

Aliases for NOTCH2 Gene

Aliases for NOTCH2 Gene

  • Notch Receptor 2 2 3 5
  • Notch 2 2 3 4
  • Neurogenic Locus Notch Homolog Protein 2 3 4
  • HN2 3 4
  • 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 Receptor 2) is a Protein Coding gene. Diseases associated with NOTCH2 include Alagille Syndrome 2 and Hajdu-Cheney Syndrome. Among its related pathways are ERK Signaling and Presenilin-Mediated Signaling. Gene Ontology (GO) annotations related to this gene include calcium ion binding. An important paralog of this gene is NOTCH1.

UniProtKB/Swiss-Prot Summary for NOTCH2 Gene

  • Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) 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 (PubMed:21378985, PubMed:21378989). 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 , Rfam classification 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
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J120066 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 501.9 +32.5 32478 4.6 PHF8 TEAD4 ZFX ZNF639 ZIC2 ZBTB10 CLOCK ZBTB26 KLF7 CHD1 NOTCH2 LOC101929178 lnc-PHGDH-4 piR-40331-001
GH01J120101 Promoter/Enhancer 0.6 Ensembl dbSUPER 500.7 -0.2 -222 0.4 KLF1 LOC105378939 NOTCH2 LOC105378940
GH01J120100 Promoter/Enhancer 0.6 Ensembl dbSUPER 500.7 +1.1 1078 1.8 KLF1 LOC105378939 NOTCH2 lnc-NOTCH2-3
GH01J120098 Promoter/Enhancer 0.6 EPDnew dbSUPER 500.7 +0.0 30 0.1 KLF1 LOC105378939 NOTCH2 lnc-NOTCH2-3
GH01J119985 Enhancer 1.6 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 12.5 +109.4 109362 12 ZNF217 ZSCAN5C JUND FOS ZNF10 ZIC2 ZNF423 KLF7 ZNF830 CTBP1 lnc-ADAM30-1 piR-37475-001 piR-38380-001 piR-47635-001 NOTCH2 ADAM30 ZNF697 piR-39259-001 piR-47741-001
- 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

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NOTCH2

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

Genomic Locations for NOTCH2 Gene

Genomic Locations for NOTCH2 Gene
chr1:119,911,553-120,100,779
(GRCh38/hg38)
Size:
189,227 bases
Orientation:
Minus strand
chr1:120,454,176-120,612,317
(GRCh37/hg19)
Size:
158,142 bases
Orientation:
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:
    Q04721-NOTC2_HUMAN
    Recommended name:
    Neurogenic locus notch homolog protein 2
    Protein Accession:
    Q04721
    Secondary Accessions:
    • Q5T3X7
    • Q99734
    • Q9H240

    Protein attributes for NOTCH2 Gene

    Size:
    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). Interacts with MINAR1; this interaction increases MINAR1 stability and function (PubMed:29329397). Interacts with NOTCH2NL (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC); leading to enhance Notch signaling pathway in a non-cell-autonomous manner (PubMed:29856954). Interacts with MDK; this interaction mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3 (PubMed:18469519).

    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 (By similarity). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (By similarity). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (By similarity). 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 Asn46, Asn155, Ser613, Asn733, Asn1102, and Asn1465
  • Ubiquitination at Lys1705
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • NOTC2_HUMAN (1553)

Antibody Products

  • Abcam antibodies for NOTCH2

Protein Products

  • Signalway Proteins for NOTCH2
  • ProSci Proteins for NOTCH2
  • Abcam proteins for NOTCH2

No data available for DME Specific Peptides for NOTCH2 Gene

Domains & Families for NOTCH2 Gene

Gene Families for NOTCH2 Gene

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

Protein Domains for NOTCH2 Gene

Blocks:
  • Ankyrin repeat signature
  • Aspartic acid and asparagine hydroxylation site
  • EGF-like calcium-binding
  • Type II EGF-like signature
  • LIN-12/notch repeat (LNR) signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NOTCH2 Gene

GenScript: Design optimal peptide antigens:
  • Neurogenic locus notch homolog protein 2 (NOTC2_HUMAN)
  • NOTCH2 protein (Q6IQ50_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q04721

UniProtKB/Swiss-Prot:

NOTC2_HUMAN :
  • Belongs to the NOTCH family.
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 Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) 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 (PubMed:21378985, PubMed:21378989). 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,IEA 10079256
GO:0019899 enzyme binding IEA --
GO:0038023 signaling receptor activity NAS 9244302
GO:0051059 NF-kappaB binding IEA --
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

COMPARTMENTS
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 4
golgi apparatus 4
cytoskeleton 2
mitochondrion 2
cytosol 2
endosome 1
lysosome 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

Pathways by source for NOTCH2 Gene

SIGNOR curated interactions for NOTCH2 Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001709 cell fate determination TAS 9244302
GO:0001947 heart looping IEA --
GO:0002011 morphogenesis of an epithelial sheet IEA --
genes like me logo Genes that share ontologies with NOTCH2: view

Drugs & Compounds for NOTCH2 Gene

(10) Drugs for NOTCH2 Gene - From: ApexBio and 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

(6) ApexBio Compounds for NOTCH2 Gene

Compound Action Cas Number
BMS-983970 1584713-87-0
FLI-06 313967-18-9
LY3039478 Notch inhibitor, novel and potent 1421438-81-4
LY-900009 Potent Notch inhibitor 209984-68-9
PF-03084014 γ-secretase inhibitor 865773-15-5
Z-Ile-Leu-aldehyde 161710-10-7
genes like me logo Genes that share compounds with NOTCH2: view

Drug Products

Transcripts for NOTCH2 Gene

mRNA/cDNA for NOTCH2 Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

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
NOTCH2

Expression for NOTCH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NOTCH2

SOURCE GeneReport for Unigene cluster for NOTCH2 Gene:

Hs.487360

mRNA Expression by UniProt/SwissProt for NOTCH2 Gene:

Q04721-NOTC2_HUMAN
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
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
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
Thorax:
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • abdominal wall
  • biliary tract
  • gallbladder
  • intestine
  • kidney
  • liver
  • pancreas
Pelvis:
  • pelvis
  • penis
  • testicle
  • ureter
  • urethra
  • urinary bladder
Limb:
  • 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
General:
  • 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
chimpanzee
(Pan troglodytes)
Mammalia NOTCH2 30
  • 99.76 (n)
dog
(Canis familiaris)
Mammalia NOTCH2 31 30
  • 91.83 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NOTCH2 31 30
  • 91 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Notch2 17 31 30
  • 87.14 (n)
oppossum
(Monodelphis domestica)
Mammalia NOTCH2 31
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Notch2 30
  • 86.84 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia NOTCH2 31
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves NOTCH2 31 30
  • 74.1 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486344 30
  • 68.89 (n)
zebrafish
(Danio rerio)
Actinopterygii notch2 31 30
  • 61.03 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta N 31 32
  • 42 (a)
OneToMany
CG15388 32
  • 39 (a)
SP1070 32
  • 38 (a)
worm
(Caenorhabditis elegans)
Secernentea W02C12.1 32
  • 38 (a)
Y69H2.12 32
  • 30 (a)
F55G1.13 32
  • 29 (a)
Y69H2.2 32
  • 28 (a)
Y69H2.11 32
  • 28 (a)
F55H12.3 32
  • 27 (a)
R05G6.9 32
  • 26 (a)
lin-12 32
  • 25 (a)
mup-4 32
  • 25 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SWI6 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 41 (a)
OneToOne
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

ENSEMBL:
Gene Tree for NOTCH2 (if available)
TreeFam:
Gene Tree for NOTCH2 (if available)
Aminode:
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:

  • NOTC2_HUMAN
  • D2WEZ3_HUMAN
  • Q6IQ50_HUMAN
  • R4GN02_HUMAN

Pseudogenes.org Pseudogenes for NOTCH2 Gene

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

Variants for NOTCH2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NOTCH2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
617549 Likely Pathogenic: Hajdu-Cheney syndrome 119,915,801(-) GAA/G FRAMESHIFT_VARIANT
635423 Likely Pathogenic: Alagille syndrome 2 119,916,261(-) AG/A NONSENSE
648134 Uncertain Significance: Hajdu-Cheney syndrome 119,916,562(-) T/C MISSENSE_VARIANT
650161 Uncertain Significance: Hajdu-Cheney syndrome 119,941,562(-) A/G MISSENSE_VARIANT
656195 Uncertain Significance: Hajdu-Cheney syndrome 119,963,571(-) T/TA SPLICE_DONOR_VARIANT

Additional dbSNP identifiers (rs#s) for NOTCH2 Gene

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)
NOTCH2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NOTCH2

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

Disorders for NOTCH2 Gene

MalaCards: The human disease database

(29) MalaCards diseases for NOTCH2 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, Orphanet, DISEASES, Novoseek, and GeneCards

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

UniProtKB/Swiss-Prot

NOTC2_HUMAN
  • 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
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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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 23 41 54
  2. MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer growth. (PMID: 29329397) Ho RX … Rahimi N (Journal of molecular cell biology 2018) 3 4 54
  3. Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis. (PMID: 29856954) Fiddes IT … Haussler D (Cell 2018) 3 4 54
  4. NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis. (PMID: 29149593) Fukushima H … Inuzuka H (Molecular cell 2017) 3 4 54
  5. 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 54

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