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Genetics Home Reference: your guide to understanding genetic conditions
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NOTCH3

Reviewed May 2008

What is the official name of the NOTCH3 gene?

The official name of this gene is “notch 3.”

NOTCH3 is the gene's official symbol. The NOTCH3 gene is also known by other names, listed below.

What is the normal function of the NOTCH3 gene?

The NOTCH3 gene provides instructions for producing the Notch3 receptor protein. This receptor protein is located on the surface of the muscle cells that surround blood vessels (vascular smooth muscle cells). The Notch3 receptor protein is specific to arteries, which are blood vessels that carry blood from the heart to the rest of the body. The protein is not present in veins, which return blood to the heart. When certain molecules attach (bind) to Notch3 receptors, the receptors send signals to the nucleus of the cell. These signals then turn on (activate) particular genes within vascular smooth muscle cells. Notch3 receptors play a key role in the function and survival of vascular smooth muscle cells. These receptors are thought to be essential for the maintenance of healthy muscle cells in the brain's arteries.

Does the NOTCH3 gene share characteristics with other genes?

The NOTCH3 gene belongs to a family of genes called ANKRD (ankyrin repeat domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the NOTCH3 gene related to health conditions?

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy - caused by mutations in the NOTCH3 gene

More than 150 mutations in the NOTCH3 gene have been found to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CADASIL. Almost all of these mutations change a single protein building block (amino acid) in the Notch3 receptor. The amino acid involved in most mutations is cysteine. The addition or deletion of a cysteine molecule in a certain area of the Notch3 receptor, known as the EGF-like domain, presumably affects Notch3 receptor function in vascular smooth muscle cells. Disruption of Notch3 functioning can lead to the self-destruction (apoptosis) of these cells. Damage to vascular smooth muscle cells is thought to cause recurrent strokes and other signs and symptoms of CADASIL.

Where is the NOTCH3 gene located?

Cytogenetic Location: 19p13.2-p13.1

Molecular Location on chromosome 19: base pairs 15,159,632 to 15,200,980

The NOTCH3 gene is located on the short (p) arm of chromosome 19 between positions 13.2 and 13.1.

The NOTCH3 gene is located on the short (p) arm of chromosome 19 between positions 13.2 and 13.1.

More precisely, the NOTCH3 gene is located from base pair 15,159,632 to base pair 15,200,980 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about NOTCH3?

You and your healthcare professional may find the following resources about NOTCH3 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the NOTCH3 gene or gene products?

  • CADASIL
  • CASIL
  • Neurogenic locus notch homolog protein 3
  • NOTC3_HUMAN
  • Notch homolog 3
  • Notch homolog 3 (Drosophila)

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding NOTCH3?

amino acid ; apoptosis ; arteries ; arteriopathy ; autosomal ; autosomal dominant ; cell ; cysteine ; deletion ; domain ; gene ; leukoencephalopathy ; locus ; molecule ; muscle cells ; nucleus ; protein ; receptor ; subcortical ; vascular ; veins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Arboleda-Velasquez JF, Zhou Z, Shin HK, Louvi A, Kim HH, Savitz SI, Liao JK, Salomone S, Ayata C, Moskowitz MA, Artavanis-Tsakonas S. Linking Notch signaling to ischemic stroke. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4856-61. doi: 10.1073/pnas.0709867105. Epub 2008 Mar 17. (http://www.ncbi.nlm.nih.gov/pubmed/18347334?dopt=Abstract)
  • Dichgans M. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: phenotypic and mutational spectrum. J Neurol Sci. 2002 Nov 15;203-204:77-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12417361?dopt=Abstract)
  • Haritunians T, Boulter J, Hicks C, Buhrman J, DiSibio G, Shawber C, Weinmaster G, Nofziger D, Schanen C. CADASIL Notch3 mutant proteins localize to the cell surface and bind ligand. Circ Res. 2002 Mar 22;90(5):506-8. (http://www.ncbi.nlm.nih.gov/pubmed/11909813?dopt=Abstract)
  • Kalaria RN, Viitanen M, Kalimo H, Dichgans M, Tabira T; CADASIL Group of Vas-Cog. The pathogenesis of CADASIL: an update. J Neurol Sci. 2004 Nov 15;226(1-2):35-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15537516?dopt=Abstract)
  • Louvi A, Arboleda-Velasquez JF, Artavanis-Tsakonas S. CADASIL: a critical look at a Notch disease. Dev Neurosci. 2006;28(1-2):5-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16508299?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4854)
  • OMIM: NOTCH, DROSOPHILA, HOMOLOG OF, 3 (http://omim.org/entry/600276)
  • Rafalowska J, Dziewulska D, Fidzianska A. CADASIL: what component of the vessel wall is really a target for Notch 3 gene mutations? Neurol Res. 2004 Jul;26(5):558-62. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15265274?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2008
Published: July 21, 2014