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URL of this page: https://medlineplus.gov/genetics/gene/nsd2/

NSD2 gene

nuclear receptor binding SET domain protein 2

Normal Function

The NSD2 gene provides instructions for making at least three very similar proteins known as MMSET I, MMSET II, and RE-IIBP. These proteins are active both before and after birth in many of the body's cells and tissues. They appear to play an important role in normal development.

At least two of the proteins produced from the NSD2 gene, MMSET II and RE-IIBP, likely help regulate the activity of other genes. Studies suggest that these proteins function as histone methyltransferases, which are enzymes that modify proteins called histones. By adding a molecule called a methyl group to histones, histone methyltransferases can turn off (suppress) the activity of certain genes. Scientists are working to identify the genes targeted by the MMSET II and RE-IIBP proteins.

Health Conditions Related to Genetic Changes

Wolf-Hirschhorn syndrome

The NSD2 gene is located in a region of chromosome 4 that is deleted in people with Wolf-Hirschhorn syndrome. The features of this condition include  a characteristic facial appearance, delayed growth and development, intellectual disability, and seizures.

As a result of this deletion in chromosome 4, affected individuals are missing one copy of the NSD2 gene in each cell. A loss of the NSD2 gene probably disrupts the regulation of several other genes, although these genes have not been identified. Research shows that abnormal gene regulation during development contributes to some of the features of Wolf-Hirschhorn syndrome.

More About This Health Condition

Cancers

A chromosomal rearrangement (translocation) involving the NSD2 gene has been associated with multiple myeloma, a cancer that starts in bone marrow cells. This rearrangement is found in 15 to 20 percent of all multiple myelomas. The translocation abnormally fuses the NSD2 gene on chromosome 4 with part of another gene on chromosome 14. The fusion of these genes overactivates the NSD2 gene, which appears to promote the uncontrolled growth and division of cancer cells.

Other Names for This Gene

  • FLJ23286
  • IL5 promoter REII region-binding protein
  • KIAA1090
  • MGC176638
  • MMSET
  • multiple myeloma SET domain protein
  • NSD2_HUMAN
  • Nuclear SET domain-containing protein 2
  • Probable histone-lysine N-methyltransferase NSD2
  • Protein trithorax-5
  • REIIBP
  • trithorax/ash1-related protein 5
  • TRX5
  • WHSC1
  • Wolf-Hirschhorn syndrome candidate 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bergemann AD, Cole F, Hirschhorn K. The etiology of Wolf-Hirschhorn syndrome. Trends Genet. 2005 Mar;21(3):188-95. doi: 10.1016/j.tig.2005.01.008. Citation on PubMed
  • Chesi M, Nardini E, Lim RS, Smith KD, Kuehl WM, Bergsagel PL. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood. 1998 Nov 1;92(9):3025-34. Citation on PubMed
  • Keats JJ, Maxwell CA, Taylor BJ, Hendzel MJ, Chesi M, Bergsagel PL, Larratt LM, Mant MJ, Reiman T, Belch AR, Pilarski LM. Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients. Blood. 2005 May 15;105(10):4060-9. doi: 10.1182/blood-2004-09-3704. Epub 2005 Jan 27. Citation on PubMed or Free article on PubMed Central
  • Keats JJ, Reiman T, Belch AR, Pilarski LM. Ten years and counting: so what do we know about t(4;14)(p16;q32) multiple myeloma. Leuk Lymphoma. 2006 Nov;47(11):2289-300. doi: 10.1080/10428190600822128. Citation on PubMed
  • Kim JY, Kee HJ, Choe NW, Kim SM, Eom GH, Baek HJ, Kook H, Kook H, Seo SB. Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity. Mol Cell Biol. 2008 Mar;28(6):2023-34. doi: 10.1128/MCB.02130-07. Epub 2008 Jan 2. Citation on PubMed or Free article on PubMed Central
  • Lauring J, Abukhdeir AM, Konishi H, Garay JP, Gustin JP, Wang Q, Arceci RJ, Matsui W, Park BH. The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity. Blood. 2008 Jan 15;111(2):856-64. doi: 10.1182/blood-2007-05-088674. Epub 2007 Oct 17. Citation on PubMed or Free article on PubMed Central
  • Marango J, Shimoyama M, Nishio H, Meyer JA, Min DJ, Sirulnik A, Martinez-Martinez Y, Chesi M, Bergsagel PL, Zhou MM, Waxman S, Leibovitch BA, Walsh MJ, Licht JD. The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood. 2008 Mar 15;111(6):3145-54. doi: 10.1182/blood-2007-06-092122. Epub 2007 Dec 21. Citation on PubMed or Free article on PubMed Central
  • Stec I, Wright TJ, van Ommen GJ, de Boer PA, van Haeringen A, Moorman AF, Altherr MR, den Dunnen JT. WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma. Hum Mol Genet. 1998 Jul;7(7):1071-82. doi: 10.1093/hmg/7.7.1071. Erratum In: Hum Mol Genet 1998 Sep;7(9):1527. Citation on PubMed
  • Todoerti K, Ronchetti D, Agnelli L, Castellani S, Marelli S, Deliliers GL, Zanella A, Lombardi L, Neri A. Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma. Br J Haematol. 2005 Oct;131(2):214-8. doi: 10.1111/j.1365-2141.2005.05741.x. Citation on PubMed
  • Zanoni P, Steindl K, Sengupta D, Joset P, Bahr A, Sticht H, Lang-Muritano M, van Ravenswaaij-Arts CMA, Shinawi M, Andrews M, Attie-Bitach T, Maystadt I, Belnap N, Benoit V, Delplancq G, de Vries BBA, Grotto S, Lacombe D, Larson A, Mourmans J, Ounap K, Petrilli G, Pfundt R, Ramsey K, Blok LS, Tsatsaris V, Vitobello A, Faivre L, Wheeler PG, Wevers MR, Wojcik M, Zweier M, Gozani O, Rauch A. Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype. Genet Med. 2021 Aug;23(8):1474-1483. doi: 10.1038/s41436-021-01158-1. Epub 2021 May 3. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.