Gene: NOTCH3

Alternate names for this Gene: CADASIL|CADASIL1|CASIL|IMF2|LMNS

Gene 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).

Gene is located in Chromosome: 19

Location in Chromosome : 19p13.12

Description of this Gene: notch receptor 3

Type of Gene: protein-coding

rs797045014 in NOTCH3 gene and CADASIL Syndrome PMID 9388399 1997 Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients.

rs1323608032 in NOTCH3 gene and CEREBRAL ARTERIOPATHY, AUTOSOMAL DOMINANT, WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY, TYPE 1 PMID 10712431 2000 The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients.

PMID 12146805 2002 CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia.

PMID 11755616 2001 Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis.

PMID 19245392 2009 Acute confusional migraine may be a presenting feature of CADASIL.

PMID 15364702 2004 Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients.

PMID 9388399 1997 Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients.

PMID 15378071 2004 Detection of the founder effect in Finnish CADASIL families.

PMID 16009764 2005 Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies.

PMID 15300988 2004 Gene symbol: NOTCH3. Disease: CADASIL.

PMID 20298421 2010 EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias.

PMID 15350543 2004 CADASIL-associated Notch3 mutations have differential effects both on ligand binding and ligand-induced Notch3 receptor signaling through RBP-Jk.

PMID 15818833 2005 Gene symbol: NOTCH3. Disease: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

PMID 24000151 2013 Hypomorphic NOTCH3 alleles do not cause CADASIL in humans.

PMID 11058919 2000 Identification of a novel mutation C144F in the Notch3 gene in an Australian CADASIL pedigree.

PMID 25355838 2014 Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

PMID 10227618 1999 Quantitative MRI in CADASIL: correlation with disability and cognitive performance.

PMID 10854111 2000 Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains.

PMID 12136071 2002 C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke.

PMID 10371548 1999 Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.

PMID 11559313 2001 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.

PMID 11102981 2000 Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content.

PMID 11810186 2002 Reversible coma with raised intracranial pressure: an unusual clinical manifestation of CADASIL.

PMID 10802807 2000 Splice site mutation causing a seven amino acid Notch3 in-frame deletion in CADASIL.

PMID 12589106 2003 A novel mutation (C67Y)in the NOTCH3 gene in a Korean CADASIL patient.

PMID 12810003 2003 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.

PMID 27350778 2016 Evaluation of NOTCH3 Pro167Ser Variation in a Japanese Family with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

PMID 24139282 2014 Spectrum of NOTCH3 mutations in Korean patients with clinically suspicious cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

PMID 16717210 2006 Characteristics of CADASIL in Korea: a novel cysteine-sparing Notch3 mutation.

PMID 24929957 2014 Case report: bipolar disorder as the first manifestation of CADASIL.

PMID 26002683 2015 NOTCH3 variants in patients with subcortical vascular cognitive impairment: a comparison with typical CADASIL patients.

PMID 25980907 2015 Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014.

PMID 20935329 2011 NOTCH3 mutations and clinical features in 33 mainland Chinese families with CADASIL.

PMID 22367839 2012 Amyotrophic lateral sclerosis and frontotemporal lobar degeneration in association with CADASIL.

PMID 11784372 2002 CADASIL syndrome in a large Turkish kindred caused by the R90C mutation in the Notch3 receptor.

PMID 23649698 2013 Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL.

PMID 19242647 2009 Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese.

PMID 19252787 2009 The remarkably variable expressivity of CADASIL: report of a minimally symptomatic man at an advanced age.

PMID 21852154 2013 Diversity of stroke presentation in CADASIL: study from patients harboring the predominant NOTCH3 mutation R544C.

PMID 23602593 2013 A homozygous NOTCH3 mutation p.R544C and a heterozygous TREX1 variant p.C99MfsX3 in a family with hereditary small vessel disease of the brain.

PMID 26308724 2015 Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles.

PMID 23847153 2014 Headache among CADASIL patients with R544C mutation: prevalence, characteristics, and associations.

PMID 22664156 2012 Mutational and haplotype map of NOTCH3 in a cohort of Italian patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

rs34338511 in NOTCH3 gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs1555725043 in NOTCH3 gene and LATERAL MENINGOCELE SYNDROME PMID 26754023 2016 Lateral meningocele (Lehman) syndrome: A child with a novel NOTCH3 mutation.

PMID 25394726 2015 Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome.

rs367543285 in NOTCH3 gene and MYOFIBROMATOSIS, INFANTILE, 2 PMID 23731542 2013 Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis.

rs34338511 in NOTCH3 gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs34338511 in NOTCH3 gene and Triglycerides measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.