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Genetics Home Reference: your guide to understanding genetic conditions
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NOTCH2

Reviewed April 2010

What is the official name of the NOTCH2 gene?

The official name of this gene is “notch 2.”

NOTCH2 is the gene's official symbol. The NOTCH2 gene is also known by other names, listed below.

What is the normal function of the NOTCH2 gene?

The NOTCH2 gene provides instructions for making a protein called Notch2, a member of the Notch family of receptors. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals between neighboring cells that affect cell development and function.

The Notch2 receptor has five ligands: Jagged-1 and 2, and Delta-like 1, 3, and 4. Together, these proteins send signals that are important for development before birth. Research indicates that signals triggered by the interaction between Notch2 and its ligands are important for the development of cells destined to be part of the heart, liver, kidney, teeth, and other structures in a growing embryo. After birth, Notch2 signaling is involved in tissue repair.

How are changes in the NOTCH2 gene related to health conditions?

Alagille syndrome - caused by mutations in the NOTCH2 gene

At least two mutations in the NOTCH2 gene that cause Alagille syndrome have been identified. These mutations probably result in a Notch2 receptor that is abnormally small or folded into the wrong 3-dimensional shape. The defective protein may impair the interaction between the Notch2 receptor and one of its ligands, Jagged-1, which would disrupt signaling. Disrupted signaling is believed to cause errors in development of the heart, liver, kidney, and other parts of the body, resulting in the signs and symptoms of Alagille syndrome.

cancers - associated with the NOTCH2 gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are not inherited, are called somatic mutations. Somatic mutations of the NOTCH2 gene have been found in some cancers of immune system cells (lymphomas). These mutations appear to increase the activity (expression) of the NOTCH2 gene. In some affected cells, extra copies of the mutated gene have been found, further increasing gene activity. The increased gene expression may lead to uncontrolled cell growth and cell division in immune system cells, which can result in the development of a cancerous tumor.

Where is the NOTCH2 gene located?

Cytogenetic Location: 1p13-p11

Molecular Location on chromosome 1: base pairs 120,454,175 to 120,612,316

The NOTCH2 gene is located on the short (p) arm of chromosome 1 between positions 13 and 11.

The NOTCH2 gene is located on the short (p) arm of chromosome 1 between positions 13 and 11.

More precisely, the NOTCH2 gene is located from base pair 120,454,175 to base pair 120,612,316 on chromosome 1.

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 NOTCH2?

You and your healthcare professional may find the following resources about NOTCH2 helpful.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1273/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for NOTCH2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4853%5Bgeneid%5D)

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

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((NOTCH2%5BTIAB%5D)%20OR%20(Notch%20homolog%202%5BTIAB%5D))%20OR%20((hN2%5BTIAB%5D)%20OR%20(Notch%20%20%20homolog%202%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/600275)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_NOTCH2.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4853)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4853)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=7882)

What other names do people use for the NOTCH2 gene or gene products?

  • hN2
  • NOTC2_HUMAN
  • notch 2 preproprotein
  • Notch (Drosophila) homolog 2
  • Notch homolog 2 (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 NOTCH2?

cell ; cell division ; embryo ; gene ; gene expression ; immune system ; kidney ; protein ; receptor ; syndrome ; tissue ; tumor

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

References

  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4853)
  • Gene Review: Alagille Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1273/)
  • Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, Nannya Y, Suzuki R, Ota S, Ota Y, Izutsu K, Sakata-Yanagimoto M, Hangaishi A, Yagita H, Fukayama M, Seto M, Kurokawa M, Ogawa S, Chiba S. Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci. 2009 May;100(5):920-6. (http://www.ncbi.nlm.nih.gov/pubmed/19445024?dopt=Abstract)
  • McCright B. Notch signaling in kidney development. Curr Opin Nephrol Hypertens. 2003 Jan;12(1):5-10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12496659?dopt=Abstract)
  • McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, Spinner NB. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006 Jul;79(1):169-73. Epub 2006 May 10. (http://www.ncbi.nlm.nih.gov/pubmed/16773578?dopt=Abstract)
  • Mitsiadis TA, Roméas A, Lendahl U, Sharpe PT, Farges JC. Notch2 protein distribution in human teeth under normal and pathological conditions. Exp Cell Res. 2003 Jan 15;282(2):101-9. (http://www.ncbi.nlm.nih.gov/pubmed/12531696?dopt=Abstract)
  • OMIM: NOTCH, DROSOPHILA, HOMOLOG OF, 2 (http://omim.org/entry/600275)
  • Trøen G, Wlodarska I, Warsame A, Hernández Llodrà S, De Wolf-Peeters C, Delabie J. NOTCH2 mutations in marginal zone lymphoma. Haematologica. 2008 Jul;93(7):1107-9. doi: 10.3324/haematol.11635. Epub 2008 May 27. (http://www.ncbi.nlm.nih.gov/pubmed/18508802?dopt=Abstract)
  • Varadkar P, Kraman M, Despres D, Ma G, Lozier J, McCright B. Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells. Dev Dyn. 2008 Apr;237(4):1144-52. doi: 10.1002/dvdy.21502. (http://www.ncbi.nlm.nih.gov/pubmed/18330927?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: April 2010
Published: May 20, 2013