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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NOTCH3 Gene

protein-coding GIFtS: 69
GCID: GC19M015270

notch 3

(Previous names: Notch (Drosophila) homolog 3, Notch homolog 3 (Drosophila)...)
(Previous symbol: CADASIL)

Explore 54 diseases affiliated with
NOTCH3 via

MalaCards

our new
Human Malady Compendium

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

Aliases
Notch 3¹ ² ³		Notch Homolog 3 (Drosophila)¹
CADASIL¹ ² ⁵		Neurogenic Locus Notch Homolog Protein 3²
CASIL¹ ² ⁵		Notch Homolog 3²
Notch (Drosophila) Homolog 3¹

External Ids:	HGNC: 7883¹	Entrez Gene: 4854²	Ensembl: ENSG00000074181⁷	OMIM: 600276⁵	UniProtKB: Q9UM47³

Export aliases for NOTCH3 gene to outside databases

Previous GC identifers: GC19M015649 GC19M015115 GC19M015131 GC19M014839

(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 NOTCH3:

This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch.

In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling

pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in

human, but precise interactions between these ligands and the human notch homologues remains to be determined.

Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with

subcortical infarcts and leukoencephalopathy (CADASIL). (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47

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)

Gene Wiki entry for NOTCH3 (Notch 3)

(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_000019.9 NC_018930.1 NT_011295.11

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NOTCH3 gene promoter:
AP-2gamma GATA-2 C/EBPalpha CHOP-10 Pax-3 COMP1 STAT3 AP-2beta AP-2alpha AP-2alphaA
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: NOTCH3 promoter sequence

Search SABiosciences Chromatin IP Primers for NOTCH3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOTCH3

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

Entrez Gene cytogenetic band: 19p13.2-p13.1 Ensembl cytogenetic band: 19p13.12 HGNC cytogenetic band: 19p13.2-p13.1

NOTCH3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH3 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19M015270: view genomic region (about GC identifiers)

Start:	15,270,444 bp from pter	End:	15,311,792 bp from pter
Size:	41,349 bases	Orientation:	minus strand

(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: NOTC3_HUMAN, Q9UM47 (See protein sequence)

Recommended Name: Neurogenic locus notch homolog protein 3 precursor

Size: 2321 amino acids; 243631 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

NOTCH3. Interacts with PSMA1. Interacts with HIF1AN

Subcellular location: Cell membrane; Single-pass type I membrane protein

Subcellular location: Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is

translocated to the nucleus

Secondary accessions: Q9UEB3 Q9UPL3 Q9Y6L8

Explore the universe of human proteins at neXtProt for NOTCH3: NX_Q9UM47

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

Hydroxylated by HIF1AN¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q9UM47

NOTCH3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000426.2

ENSEMBL proteins:

ENSP00000263388

Reactome Protein details: Q9UM47
Human Recombinant Protein Products for NOTCH3:

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	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NOTCH3

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	TAS	--
GO:0005576	extracellular region	TAS	--
GO:0005654	nucleoplasm	TAS	--
GO:0005789	endoplasmic reticulum membrane	TAS	--
GO:0005829	cytosol	TAS	--

NOTCH3 for ontologies About GeneDecksing

NOTCH3 Antibody Products:

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	ThermoFisher Antibodies for NOTCH3

Assay Products for NOTCH3:

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	Uscn ELISAs and CLIAs for NOTCH3

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

NOTCH3 for domains About GeneDecksing

5/13 InterPro domains/families (see all 13):

IPR010660 Notch_NOD_dom

IPR024600 DUF3454_notch

IPR001881 EGF-like_Ca-bd

IPR008297 Notch

IPR000742 EG-like_dom

Graphical View of Domain Structure for InterPro Entry Q9UM47

ProtoNet protein and cluster: Q9UM47

5 Blocks protein families:

IPB000152 Aspartic acid and asparagine hydroxylation site

IPB000800 LIN-12/notch repeat (LNR) signature

IPB001881 EGF-like calcium-binding

IPB002049 Laminin-type EGF-like domain

IPB002110 Ankyrin repeat signature

UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47

Similarity: Belongs to the NOTCH family

Similarity: Contains 5 ANK repeats

Similarity: Contains 34 EGF-like domains

Similarity: Contains 3 LNR (Lin/Notch) repeats

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: NOTC3_HUMAN, Q9UM47

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)

Genatlas biochemistry entry for NOTCH3:

Drosophila Notch homolog 3,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 translocation with acute

lymphoblastic/myeloblastic leukemia and in the decision between the endocrine and exocrine fates in the developing

pancreas

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004872	receptor activity	--	--
GO:0005509	calcium ion binding	IEA	--
GO:0005515	protein binding	IPI	17292860
GO:0019899	enzyme binding	IEA	--

NOTCH3 for ontologies About GeneDecksing

Phenotypes:
15/20 MGI mutant phenotypes (inferred from 7 alleles) (MGI details for Notch3) (see all 20):

behavior/neurological	cardiovascular system	cellular	embryogenesis	endocrine/exocrine gland
growth/size	hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism	immune system
integument	mortality/aging	muscle	nervous system	normal

NOTCH3 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for NOTCH3: Notch3^tm1Khan Notch3^tm1Grid

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for NOTCH3

miRNA Products:		miRTarBase miRNAs that target NOTCH3: hsa-mir-206 (MIRT000665)

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		hsa-miR-26a-2* hsa-miR-875-3p hsa-miR-3673 hsa-miR-136 hsa-miR-520d-5p hsa-miR-1263 hsa-miR-300 hsa-miR-24-1*

		SwitchGear 3'UTR luciferase reporter plasmid: NOTCH3 3' UTR sequence

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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH3

(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 - 5/19 super-pathways (see all 19) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Mature NOTCH heterodimer traffics to the plasma membrane

Mature NOTCH heterodimer traffics to the plasma membrane	1.00	A third proteolytic cleavage releases NICD	0.44
Transport of fringe-modified NOTCH to plasma membrane	1.00	NICD traffics to nucleus	0.31
Transport of NOTCH precursor to Golgi	1.00	Notch-HLH transcription pathway	0.31
Pre-NOTCH Processing in the Endoplasmic Reticulum	0.67

Notch Signaling Pathway

	Notch Signaling Pathway	1.00			Delta-Notch Signaling Pathway	0.27
	Notch signaling pathway	0.82

Generic Transcription Pathway

Generic Transcription Pathway

1.00

Gene Expression

0.46

Pre-NOTCH Processing in Golgi

Pre-NOTCH Processing in Golgi

1.00

Pre-NOTCH Expression and Processing

0.55

Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant

Signaling by NOTCH

0.77

Notch Signaling

0.23

Pathway sources
See GeneCards unified pathways
Show all pathways

4 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for NOTCH3

	Notch Signaling
	Molecular Mechanisms of Cancer
	Presenilin-Mediated Signaling
	Epithelial Adherens Junctions

3 Cell Signaling Technology (CST) Pathways for NOTCH3

	Wnt / Hedgehog / Notch
	Angiogenesis
	Neuroscience

4 BioSystems Pathways for NOTCH3

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

5/17 Reactome Pathways for NOTCH3 (see all 17)

	Pre-NOTCH Expression and Processing
	A third proteolytic cleavage releases NICD
	Notch-HLH transcription pathway
	NOTCH3 mRNA translation controlled by miRNAs
	Signal Transduction

2 Kegg Pathways (Kegg details for NOTCH3):

	Dorso-ventral axis formation
	Notch signaling pathway

NOTCH3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NOTCH3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/55 Interacting proteins for NOTCH3 (Q9UM47^{1, 2, 3} ENSP00000263388⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 55)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
JAG1	P78504²^,³, ENSP00000254958⁴	MINT-8360953 I2D: score=3 STRING: ENSP00000254958
CSNK2B	P67870²^,³	MINT-8253473 I2D: score=2
JAG2	Q9Y219³, ENSP00000328169⁴	I2D: score=3 STRING: ENSP00000328169
MAML1	Q92585³, ENSP00000292599⁴	I2D: score=3 STRING: ENSP00000292599
CHUK	O15111³, ENSP00000359424⁴	I2D: score=2 STRING: ENSP00000359424

About this table

Gene Ontology (GO): 5/12 biological process terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006355	regulation of transcription, DNA-dependent	IEA	--
GO:0006367	transcription initiation from RNA polymerase II promoter	TAS	--
GO:0007219	Notch signaling pathway	TAS	--
GO:0007220	Notch receptor processing	TAS	--
GO:0010467	gene expression	TAS	--

NOTCH3 for ontologies About GeneDecksing

(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

NOTCH3 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for NOTCH3
3 Novoseek chemical compound relationships for NOTCH3 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cysteine	58.1	29	19043263 (2), 16256149 (2), 15714997 (1), 17331978 (1), 17629811 (1), 19293235 (1), 16796587 (1), 19006080 (1), 15304596 (1), 11559313 (1), 17622327 (1), 10854111 (1), 11244211 (1), 18273901 (1), 11706120 (1), 16717210 (1), 18022198 (1), 19539236 (1) (see top 4)
arginine	14.1	3	15714997 (1), 11559313 (1)
calcium	1.73	1	10024441 (1)

Search CenterWatch for drugs/clinical trials and news about NOTCH3 / NOTC3

(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, Sirion Biotech, 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 NOTCH3 gene:

NM_000435.2

Unigene Cluster for NOTCH3:

Notch 3

Hs.8546 [show with all ESTs]

Unigene Representative Sequence: U97669

1 Ensembl transcript including schematic representation, and UCSC links where relevant:

ENST00000263388(uc002nan.3 uc002nao.1)

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Additional cDNA sequence:

AB209447.1 U97669.1

5 DOTS entries:

DT.217396 DT.91963540 DT.100815125 DT.75121130 DT.91646701

24/277 AceView cDNA sequences (see all 277):

AI274902 BM021193 BM841037 CA446395 CN483616 BU956081 BU553672 AI473478

BU556839 BU846477 CB270591 AI559175 AI091531 BI523794 T63511 AA301460

BM021466 BU859204 BI052410 AW194070 BQ919557 CR611252 BF435534 AI969777

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH3 About this scheme

ExUns:	1	^	2	^	3	^	4	^	5	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16	^	17	^	18	^	19	^	20a	·	20b	^	21	^	22	^	23a	·	23b	^	24	^
SP1:																																							-
SP2:																													-										-
SP3:

ExUns:	25	^	26	^	27	^	28	^	29	^	30	^	31	^	32
SP1:
SP2:
SP3:

ECgene alternative splicing isoforms for NOTCH3

(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

NOTCH3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: GCAGAATAGA

About this image

NOTCH3 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10/45 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 45)

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Endothelium

Veins

Vascular Smooth Muscle Cells

Smooth Muscle

Heart

Aortic Arch Arteries

Vascular Smooth Muscle Cells

Myocardium, Neural Crest, Smooth Muscle

Heart

Endocardium

Vascular Smooth Muscle Cells

Smooth Muscle

Kidney

Afferent Arteriole

Juxtaglomerular Cells

Kidney, Smooth Muscle

Limb

Forelimb Dorsal Muscles

Mononuclear Myocytes

Skeletal Muscle

Limb

Forelimb Dorsal Muscles

Myoblasts

Skeletal Muscle

Limb

Forelimb Ventral Muscles

Mononuclear Myocytes

Skeletal Muscle

Limb

Forelimb Ventral Muscles

Myoblasts

Skeletal Muscle

Limb

Hindlimb Dorsal Muscle

Mononuclear Myocytes

Skeletal Muscle

Limb

Hindlimb Dorsal Muscle

Myoblasts

Skeletal Muscle

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

PureStem™ mesenchymal progenitor E15 (Embryonic Progenitor Cell)

Adipose, Bone, Cartilage

See NOTCH3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NOTCH3

SOURCE GeneReport for Unigene cluster: Hs.8546

UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47

Tissue specificity: Ubiquitously expressed in fetal and adult tissues

SABiosciences Expression via Pathway-Focused PCR Arrays including NOTCH3:

Notch Signaling Targets in human mouse rat

Adherens Junctions in human mouse rat

Stem Cell Signaling in human mouse rat

Cell Junction PathwayFinder in human mouse rat

Notch Signaling Pathway in human mouse rat

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NOTCH3

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH3

(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 NOTCH3 gene from 5/19 species (see all 19) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
lizard (Anolis carolinensis)	Reptilia	NOTCH3⁶	--	61(a)	1 ↔ 1	2(103176143-103207872)
tropical clawed frog (Xenopus tropicalis)	Amphibia	142033487²	--	76.95(n)		142033487
zebrafish (Danio rerio)	Actinopterygii	AF152001.1²	--	75.66(n)		58066 AF152001.1
fruit fly (Drosophila melanogaster)	Insecta	SP1070³	Notch binding	38(a) (best of 2)		27D2 --
worm (Caenorhabditis elegans)	Secernentea	W02C12.1³	EGF-like protein	37(a) (best of 7)		IV(4008218-4014159) --

ENSEMBL Gene Tree for NOTCH3 (if available)
TreeFam Gene Tree for NOTCH3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for NOTCH3 gene

NOTCH4² SNED1² NOTCH1² DLL3² DLL4² JAG2² CRB2² NOTCH2²

JAG1² DNER² CRB1² DLL1²

18 SIMAP similar genes for NOTCH3 using alignment to 5 protein entries: NOTC3_HUMAN (see all proteins):

SLIT2 ACAN F9 p22 factor IX F9 NOTCH2 CRB1

SVEP1 SLIT3 F9 SNED1 FBLN7 DLK2

NOTCH1 VCAN JAG1 EYS CUBN NCAN

NOTCH3 for paralogs About GeneDecksing

(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

SNP ID	Valid	Clinical significance	Chr 19 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28933698^1,2	C	pathogenic	15299815(-)	`TCACCT/CGTATC`	2	/R /C	mis¹ ese³		2		NA	4
rs28933697^1,2	C	pathogenic	15302906(-)	`CCTTCC/TGCTGC`	2	R C	mis¹ ese³		2		NA	4
rs28933696^1,2	C	pathogenic	15302945(-)	`CCTGCC/TGCCAT`	2	R C	mis¹ ese³		2		NA	4
rs35769976^1,2	C,F	unknown	15291576(-)	`CTGGGG/CCCTAT`	2	/P /A	mis¹		11		NA WA EU	5179
rs138092938^1,2	C	other	15289677(+)	`GACCCG/AGGCTA`	2	/P /L	mis¹		1		NA	3818
rs191283227^1,2		--	15270003(+)	`ACTCAA/CTTAAC`	1	--	ds500¹		0	--	--	--	--
rs183863721^1,2		--	15270035(+)	`GAGCCA/GAGATA`	1	--	ds500¹		0	--	--	--	--
rs4809026^1,2	C,F,A	--	15270059(+)	`TCAAGG/CAGCCA`	1	--	ds500¹		9		NA CSA WA EA	369
rs139155522^1,2		--	15270149(+)	`TCGAAC/TTGGCC`	1	--	ds500¹		0	--	--	--	--
rs149949800^1,2		--	15270232(+)	`AGAAAA/GTTCTC`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for NOTCH3 (15270444 - 15311792 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for NOTCH3
1 CNV: 47932
Human Gene Mutation Database (HGMD): NOTCH3

Locus Specific Mutation Databases (LSDB): NOTCH3

SABiosciences Cancer Mutation PCR Assays

1 SABiosciences qBiomarker Copy Number PCR Array containing NOTCH3:

Oncogenes & Tumor Suppressor Genes 384HC

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing NOTCH3

DNA2.0 Custom Variant and Variant Library Synthesis for NOTCH3

(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

NOTCH3 for disorders           About GeneDecksing

OMIM gene information: 600276
OMIM disorders: 125310
UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47

Defects in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and

leukoencephalopathy (CADASIL) [MIM:125310]. CADASIL causes a type of stroke and dementia of which key features include

recurrent subcortical ischemic events and vascular dementia. The disorder affects relatively young adults of both

sexes. Mutations affect highly conserved cysteine residues within epidermal growth factor (EGF)-like repeat domains in

the extracellular part of the receptor

20/54 diseases for NOTCH3 (see all 54): About MalaCards

cadasil cerebral arteriopathy with subcortical infarcts and leukoencephalopathy cerebritis hemiplegic migraine

pseudobulbar palsy arterial occlusive disease cerebrovascular accident migraine

cerebrovascular disease cerebral infarction dementia migraine with aura

acute lymphoblastic leukemia basal cell carcinoma multiple sclerosis vascular dementia

lymphoblastic leukemia myocardial infarction renal cell carcinoma lymphoblastic lymphoma

5 diseases from the University of Copenhagen DISEASES database for NOTCH3:

Cadasil Vascular dementia Migraine Cerebrovascular accident

Pseudobulbar palsy

10/27 Novoseek disease relationships for NOTCH3 gene (see all 27) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cadasil	99.3	380	15857853 (5), 10766655 (5), 11391502 (5), 16580020 (5) (see all 99)
infarct	87.7	115	18572291 (2), 12417361 (2), 16949066 (2), 16580020 (2) (see all 99)
migraine	83	26	16492242 (6), 16426270 (3), 19018300 (2), 15313840 (1) (see all 12)
dementia vascular	82	11	11757773 (1), 11706120 (1), 11102981 (1), 15857853 (1) (see all 10)
dementia	76.1	27	11391502 (3), 11591842 (1), 10712431 (1), 10716263 (1) (see all 24)
subcortical infarction	74.7	3	16580020 (1), 19242647 (1)
infarction lacunar	74	2	17239802 (1), 12511775 (1)
stroke	73.4	33	7783868 (2), 11591842 (1), 11757773 (1), 10712431 (1) (see all 31)
cerebrovascular disease	66.2	13	11861701 (2), 11578869 (1), 19139365 (1), 12480758 (1) (see all 10)
t-all	60.4	10	11891328 (2), 12524208 (1), 18032925 (1), 16838279 (1) (see all 7)

GeneTests: NOTCH3

CADASIL

Genetic Association Database (GAD): NOTCH3
Human Genome Epidemiology (HuGE) Navigator: NOTCH3 (67 documents)

Export disorders for NOTCH3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for NOTCH3 gene, integrated from 9 sources (see all 337):
(articles sorted by number of sources associating them with NOTCH3)

Utopia: connect your pdf to the dynamic
world of online information

Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. (PubMed id 16009764)^{1, 2, 4, 9} Peters N.... Dichgans M. (2005)
Genetic, clinical and pathological studies of CADASIL in Japan: a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis. (PubMed id 12810003)^{1, 2, 9} Santa Y....Tabira T. (2003)
Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. (PubMed id 9388399)^{1, 2, 9} Joutel A.... Tournier-Lasserve E. (1997)
Notch3 gene polymorphism and ischaemic cerebrovascular disease. (PubMed id 11861701)^{1, 4, 9} Ito D....Fukuuchi Y. (2002)
A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings. (PubMed id 11559313)^{1, 2, 9} Oliveri R.L.... Quattrone A. (2001)
Yield of screening for CADASIL mutations in lacunar stroke and leukoaraiosis. (PubMed id 12511775)^{1, 4, 9} Dong Y....Markus H.S. (2003)
Lack of association between NOTCH3 gene polymorphism and cerebrovascular disease in Japanese patients. (PubMed id 12480758)^{1, 4, 9} Mizuno T....Nakajima K. (2002)
Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. (PubMed id 8878478)^{1, 2, 9} Joutel A.... Tournier-Lasserve E. (1996)
Conserved signal peptide of Notch3 inhibits interaction with proteasome. (PubMed id 17292860)^{1, 2} Zhang Y.... Wang M.M. (2007)
Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. (PubMed id 17573339)^{1, 2} Coleman M.L....Schofield C.J. (2007)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 4854	HGNC: 7883	AceView: NOTCH3	Ensembl:ENSG00000074181	euGenes: HUgn4854
ECgene: NOTCH3	Kegg: 4854	H-InvDB: NOTCH3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NOTCH3	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for NOTCH3	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOTCH3

Intellectual Property for NOTCH3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for NOTCH3 gene:
Search GeneIP for patents involving NOTCH3

GeneCards and IP:
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Lymphoma
Dementia
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INFARCT
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STROKE
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