U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from PubMed

    • Showing Current items.

    NOTCH3 notch receptor 3 [ Homo sapiens (human) ]

    Gene ID: 4854, updated on 8-Apr-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    NOTCH3provided by HGNC
    Official Full Name
    notch receptor 3provided by HGNC
    Primary source
    HGNC:HGNC:7883
    See related
    Ensembl:ENSG00000074181 MIM:600276; AllianceGenome:HGNC:7883
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IMF2; LMNS; CASIL; CADASIL; CADASIL1
    Summary
    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]
    Expression
    Broad expression in fat (RPKM 35.4), placenta (RPKM 33.8) and 22 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See NOTCH3 in Genome Data Viewer
    Location:
    19p13.12
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (15159038..15200995, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (15283989..15325912, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (15269849..15311806, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 782, pseudogene Neighboring gene olfactory receptor family 10 subfamily B member 1 pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15281145-15281735 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10267 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15291996-15292515 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15292516-15293034 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15296283-15296783 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15305376-15305876 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15305877-15306377 Neighboring gene microRNA 6795 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:15310876-15311102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15311689-15312190 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15312191-15312690 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15333321-15334017 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10268 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15343009-15343510 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10269 Neighboring gene epoxide hydrolase 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15361355-15362226 Neighboring gene bromodomain containing 4 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:15373316-15373494 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:15374509-15375008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:15376180-15376680 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:15385287-15385786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14182 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14183 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15409795-15410322 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:15410749-15411456 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10270 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10271 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10273 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10274 Neighboring gene uncharacterized LOC124904643 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:15443616-15444232 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10276 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14184 Neighboring gene A-kinase anchoring protein 8

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    Go to the top of the pageHelp

    Related articles in PubMed

    1. [Mechanism of Notch3 signaling pathway regulating the differentiation of aortic dissection vascular stem cells into smooth muscle cells]. Han Y, et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2023 May. PMID 37308231
    2. Structural changes in NOTCH3 induced by CADASIL mutations: Role of cysteine and non-cysteine alterations. Lee SJ, et al. J Biol Chem, 2023 Jun. PMID 37209821, Free PMC Article
    3. Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment. Huang K, et al. BMC Cancer, 2023 Jan 16. PMID 36647017, Free PMC Article
    4. Phenotypic variability in 446 CADASIL patients: Impact of NOTCH3 gene mutation location in addition to the effects of age, sex and vascular risk factors. Dupé C, et al. J Cereb Blood Flow Metab, 2023 Jan. PMID 36254369, Free PMC Article
    5. Clinical features and spectrum of NOTCH3 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mönkäre S, et al. Acta Neurol Scand, 2022 Nov. PMID 36086804, Free PMC Article

    See all (480) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.
      Title: Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.
    2. NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.
      Title: NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.
    3. LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma.
      Title: LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma.
    4. Progress to Clarify How NOTCH3 Mutations Lead to CADASIL, a Hereditary Cerebral Small Vessel Disease.
      Title: Progress to Clarify How NOTCH3 Mutations Lead to CADASIL, a Hereditary Cerebral Small Vessel Disease.
    5. DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells.
      Title: DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells.
    6. Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.
      Title: Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.
    7. Association of NOTCH3 Variant Position With Stroke Onset and Other Clinical Features Among Patients With CADASIL.
      Title: Association of NOTCH3 Variant Position With Stroke Onset and Other Clinical Features Among Patients With CADASIL.
    8. The m6A reader IGF2BP3 preserves NOTCH3 mRNA stability to sustain Notch3 signaling and promote tumor metastasis in nasopharyngeal carcinoma.
      Title: The m6A reader IGF2BP3 preserves NOTCH3 mRNA stability to sustain Notch3 signaling and promote tumor metastasis in nasopharyngeal carcinoma.
    9. The cysteine-altering p.R544C variant in the NOTCH3 gene is a probable candidate for blood pressure and relevant traits in the Taiwan Biobank.
      Title: The cysteine-altering p.R544C variant in the NOTCH3 gene is a probable candidate for blood pressure and relevant traits in the Taiwan Biobank.
    10. HIV-1 subtype B Tat enhances NOTCH3 signaling in astrocytes to mediate oxidative stress, inflammatory response, and neuronal apoptosis.
      Title: HIV-1 subtype B Tat enhances NOTCH3 signaling in astrocytes to mediate oxidative stress, inflammatory response, and neuronal apoptosis.
    Submit: New GeneRIF Correction See all GeneRIFs (427)

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cadherin binding HDA PubMed 
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables enzyme binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Notch signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in artery morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in axon guidance IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in forebrain development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glomerular capillary formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuroblast differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron fate commitment IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of miRNA transcription IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of smooth muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of receptor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

    Go to the top of the page Help
    Preferred Names
    neurogenic locus notch homolog protein 3
    Names
    Notch homolog 3
    notch 3

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009819.1 RefSeqGene

      Range
      4987..46944
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000435.3 → NP_000426.2  neurogenic locus notch homolog protein 3 precursor

      See identical proteins and their annotated locations for NP_000426.2

      Status: REVIEWED

      Source sequence(s)
      AC004257, AC004663, U97669
      Consensus CDS
      CCDS12326.1
      UniProtKB/Swiss-Prot
      Q9UEB3, Q9UM47, Q9UPL3, Q9Y6L8
      Related
      ENSP00000263388.1, ENST00000263388.7
      Conserved Domains (11) summary
      smart00179
      Location:657 → 686
      EGF_CA; Calcium-binding EGF-like domain
      COG0666
      Location:1777 → 1893
      ANKYR; Ankyrin repeat [Signal transduction mechanisms]
      cd00054
      Location:158 → 195
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:1866 → 1992
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam00066
      Location:1425 → 1459
      Notch; LNR domain
      pfam06816
      Location:1508 → 1557
      NOD; NOTCH protein
      pfam07684
      Location:1578 → 1637
      NODP; NOTCH protein
      pfam11936
      Location:2212 → 2273
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:1910 → 2002
      Ank_2; Ankyrin repeats (3 copies)
      pfam13857
      Location:1858 → 1913
      Ank_5; Ankyrin repeats (many copies)
      sd00045
      Location:1905 → 1936
      ANK; ANK repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      15159038..15200995 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005259924.5 → XP_005259981.1  neurogenic locus notch homolog protein 3 isoform X1

      Conserved Domains (10) summary
      COG0666
      Location:1725 → 1841
      ANKYR; Ankyrin repeat [Signal transduction mechanisms]
      cd00054
      Location:158 → 195
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00204
      Location:1814 → 1940
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      pfam00066
      Location:1373 → 1407
      Notch; LNR domain
      pfam06816
      Location:1456 → 1505
      NOD; NOTCH protein
      pfam07684
      Location:1526 → 1585
      NODP; NOTCH protein
      pfam11936
      Location:2160 → 2221
      DUF3454; Domain of unknown function (DUF3454)
      pfam12796
      Location:1858 → 1950
      Ank_2; Ankyrin repeats (3 copies)
      pfam13857
      Location:1806 → 1861
      Ank_5; Ankyrin repeats (many copies)
      sd00045
      Location:1853 → 1884
      ANK; ANK repeat [structural motif]

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      15283989..15325912 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321104.1 → XP_054177079.1  neurogenic locus notch homolog protein 3 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UM47.2 GenPept UniProtKB/Swiss-Prot:Q9UM47

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous