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URL of this page: https://medlineplus.gov/genetics/gene/nsd1/

NSD1 gene

nuclear receptor binding SET domain protein 1

Normal Function

The NSD1 gene provides instructions for making a protein that functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify structural proteins called histones, which attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases control (regulate) the activity of certain genes and can turn them on and off as needed. The NSD1 enzyme controls the activity of genes involved in normal growth and development, although most of these genes have not been identified.

Health Conditions Related to Genetic Changes

Sotos syndrome

More than 380 mutations in the NSD1 gene have been identified in people with Sotos syndrome. The most common mutation in the Japanese population deletes genetic material from the region of chromosome 5 that contains the NSD1 gene. In most other populations, mutations within the gene itself are more frequent. These mutations include insertions or deletions of a small amount of DNA and changes in single DNA building blocks (base pairs) that make up the gene. Most mutations prevent one copy of the NSD1 gene from making any enzyme or lead to the production of an abnormally small, nonfunctional version of the enzyme. Research suggests that a reduced amount of the NSD1 enzyme disrupts the normal activity of genes involved in growth and development. However, it remains unclear exactly how a shortage of this enzyme during development leads to overgrowth, learning disabilities, and the other signs and symptoms of Sotos syndrome.

More About This Health Condition

Cancers

A change involving the NSD1 gene is associated with a blood cancer called childhood acute myeloid leukemia. This change occurs when part of chromosome 5 breaks off and reattaches to part of chromosome 11. This change is acquired during a person's lifetime and is present only in cancer cells. This type of genetic change, called a somatic mutation, is not inherited. The rearrangement of genetic material involved in childhood acute myeloid leukemia, known as a translocation, abnormally fuses the NSD1 gene on chromosome 5 with the NUP98 gene on chromosome 11. Research shows that the fused NUP98-NSD1 gene turns on genes that promote the growth of immature blood cells and blocks processes that would turn the genes off. The resulting overgrowth of these immature cells leads to development of acute myeloid leukemia.

A different type of alteration involving the NSD1 gene is associated with a cancer of nerve tissue called neuroblastoma and a type of brain cancer called glioma. This alteration, known as promoter hypermethylation, turns off the production of the NSD1 enzyme. Researchers speculate that without NSD1, the activity of one or more genes involved in cell growth and division is uncontrolled. As a result, the cells can grow and divide unchecked, leading to the development of cancer.

Other Names for This Gene

  • androgen receptor-associated coregulator 267
  • ARA267
  • histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific
  • NR-binding SET domain containing protein
  • NSD1_HUMAN
  • nuclear receptor-binding Su-var, Enhancer of zeste and Trithorax domain protein 1
  • SOTOS1

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

  • Berdasco M, Ropero S, Setien F, Fraga MF, Lapunzina P, Losson R, Alaminos M, Cheung NK, Rahman N, Esteller M. Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21830-5. doi: 10.1073/pnas.0906831106. Epub 2009 Dec 14. Citation on PubMed or Free article on PubMed Central
  • Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):24-31. doi: 10.1002/ajmg.c.30061. Citation on PubMed
  • Jaju RJ, Fidler C, Haas OA, Strickson AJ, Watkins F, Clark K, Cross NC, Cheng JF, Aplan PD, Kearney L, Boultwood J, Wainscoat JS. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood. 2001 Aug 15;98(4):1264-7. doi: 10.1182/blood.v98.4.1264. Citation on PubMed
  • Kudithipudi S, Lungu C, Rathert P, Happel N, Jeltsch A. Substrate specificity analysis and novel substrates of the protein lysine methyltransferase NSD1. Chem Biol. 2014 Feb 20;21(2):226-37. doi: 10.1016/j.chembiol.2013.10.016. Epub 2014 Jan 9. Citation on PubMed
  • Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Hasegawa T, Chinen Y, Tomita Ha HA, Kinoshita A, Mizuguchi T, Yoshiura Ki K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N. Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet. 2002 Apr;30(4):365-6. doi: 10.1038/ng863. Epub 2002 Mar 18. Citation on PubMed
  • Lucio-Eterovic AK, Singh MM, Gardner JE, Veerappan CS, Rice JC, Carpenter PB. Role for the nuclear receptor-binding SET domain protein 1 (NSD1) methyltransferase in coordinating lysine 36 methylation at histone 3 with RNA polymerase II function. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16952-7. doi: 10.1073/pnas.1002653107. Epub 2010 Sep 13. Citation on PubMed or Free article on PubMed Central
  • Pasillas MP, Shah M, Kamps MP. NSD1 PHD domains bind methylated H3K4 and H3K9 using interactions disrupted by point mutations in human sotos syndrome. Hum Mutat. 2011 Mar;32(3):292-8. doi: 10.1002/humu.21424. Citation on PubMed
  • Qiao Q, Li Y, Chen Z, Wang M, Reinberg D, Xu RM. The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation. J Biol Chem. 2011 Mar 11;286(10):8361-8368. doi: 10.1074/jbc.M110.204115. Epub 2010 Dec 31. Citation on PubMed or Free article on PubMed Central
  • Tatton-Brown K, Cole TRP, Rahman N. Sotos Syndrome. 2004 Dec 17 [updated 2022 Dec 1]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1479/ Citation on PubMed
  • Tatton-Brown K, Douglas J, Coleman K, Baujat G, Cole TR, Das S, Horn D, Hughes HE, Temple IK, Faravelli F, Waggoner D, Turkmen S, Cormier-Daire V, Irrthum A, Rahman N; Childhood Overgrowth Collaboration. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet. 2005 Aug;77(2):193-204. doi: 10.1086/432082. Epub 2005 Jun 7. Citation on PubMed or Free article on PubMed Central
  • Tatton-Brown K, Rahman N. The NSD1 and EZH2 overgrowth genes, similarities and differences. Am J Med Genet C Semin Med Genet. 2013 May;163C(2):86-91. doi: 10.1002/ajmg.c.31359. Epub 2013 Apr 16. Citation on PubMed or Free article on PubMed Central
  • Wang GG, Cai L, Pasillas MP, Kamps MP. NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol. 2007 Jul;9(7):804-12. doi: 10.1038/ncb1608. Epub 2007 Jun 24. Citation on PubMed

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