NOTCH3 notch receptor 3 [Homo sapiens (human)] - Gene

Summary

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
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Genomic context

Location:: 19p13.12

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (15159038..15200995, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (15283989..15325912, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (15269849..15311806, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression.
Title: Exploiting branched-chain amino acid metabolism and NOTCH3 expression to predict and target colorectal cancer progression.
Clinical and neuroradiological spectrum of biallelic variants in NOTCH3.
Title: Clinical and neuroradiological spectrum of biallelic variants in NOTCH3.
NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke.
Title: NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke.
Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.
Title: Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.
Phenotypes Associated with NOTCH3 Cysteine-Sparing Mutations in Patients with Clinical Suspicion of CADASIL: A Systematic Review.
Title: Phenotypes Associated with NOTCH3 Cysteine-Sparing Mutations in Patients with Clinical Suspicion of CADASIL: A Systematic Review.
Mutant NOTCH3ECD Triggers Defects in Mitochondrial Function and Mitophagy in CADASIL Cell Models.
Title: Mutant NOTCH3ECD Triggers Defects in Mitochondrial Function and Mitophagy in CADASIL Cell Models.
A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.
Title: A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.
Nailfold capillary measurements correlated to NOTCH3 R544C mutation in preclinical CADASIL patients.
Title: Nailfold capillary measurements correlated to NOTCH3 R544C mutation in preclinical CADASIL patients.
Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma.
Title: Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma.
Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.
Title: Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.

Submit: New GeneRIF Correction See all GeneRIFs (437)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 MedGen: C4551768 OMIM: 125310 GeneReviews: CADASIL	Compare labs
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy MedGen: C0751587 GeneReviews: CADASIL	Compare labs
Lateral meningocele syndrome MedGen: C1851710 OMIM: 130720 GeneReviews: NOTCH3-Related Lateral Meningocele Syndrome	Compare labs
Myofibromatosis, infantile, 2 MedGen: C3809084 OMIM: 615293 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NOTCH3_362 (e-PCR)
- UniSTS:277536

D19S923 (e-PCR), detects polymorphism
- UniSTS:34863

PMC122602P1 (e-PCR)
- UniSTS:270400

SHGC-57293 (e-PCR)
- UniSTS:52587

G62127 (e-PCR)
- UniSTS:139187

D19S1009 (e-PCR)
- UniSTS:20959

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cadherin binding	HDA more info	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

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Preferred Names: neurogenic locus notch homolog protein 3

Names: Notch homolog 3; notch 3

NCBI Reference Sequences (RefSeq)

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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

NG_009819.1 RefSeqGene

Range

4987..46944

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

15159038..15200995 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]