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Genetics Home Reference: your guide to understanding genetic conditions
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NSD1

Reviewed February 2015

What is the official name of the NSD1 gene?

The official name of this gene is “nuclear receptor binding SET domain protein 1.”

NSD1 is the gene's official symbol. The NSD1 gene is also known by other names, listed below.

What is the normal function of the NSD1 gene?

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 protein controls the activity of genes involved in normal growth and development, although most of these genes have not been identified.

Does the NSD1 gene share characteristics with other genes?

The NSD1 gene belongs to a family of genes called chromatin-modifying enzymes (chromatin-modifying enzymes). It also belongs to a family of genes called PHF (PHD-type zinc fingers).

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 NSD1 gene related to health conditions?

Sotos syndrome - caused by mutations in the NSD1 gene

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 protein or lead to the production of an abnormally small, nonfunctional version of the protein. Research suggests that a reduced amount of NSD1 protein disrupts the normal activity of genes involved in growth and development. However, it remains unclear exactly how a shortage of this protein during development leads to overgrowth, learning disabilities, and the other signs and symptoms of Sotos syndrome.

cancers - associated with the NSD1 gene

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 protein. 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.

Weaver syndrome - associated with the NSD1 gene

At least three NSD1 gene mutations have been reported in people diagnosed with Weaver syndrome. This condition is similar to Sotos syndrome (described above), with characteristic features including bone overgrowth, a distinctive facial appearance, and joint problems. People with Weaver syndrome have an increased risk of developing cancer, but the small number of affected individuals makes the exact risk difficult to determine.

The NSD1 gene mutations associated with Weaver syndrome apparently impair the normal regulation of gene activity, leading to the signs and symptoms of this disorder. Some researchers believe that these cases should be classified as unusual presentations of Sotos syndrome rather than as Weaver syndrome.

Where is the NSD1 gene located?

Cytogenetic Location: 5q35

Molecular Location on chromosome 5: base pairs 177,133,024 to 177,300,212

The NSD1 gene is located on the long (q) arm of chromosome 5 at position 35.

The NSD1 gene is located on the long (q) arm of chromosome 5 at position 35.

More precisely, the NSD1 gene is located from base pair 177,133,024 to base pair 177,300,212 on chromosome 5.

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 NSD1?

You and your healthcare professional may find the following resources about NSD1 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 NSD1 gene or gene products?

  • 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

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 NSD1?

acute ; acute myeloid leukemia ; cancer ; cell ; chromosome ; disabilities ; DNA ; domain ; enhancer ; gene ; glioma ; histone ; inherited ; joint ; leukemia ; lysine ; methyl ; methylation ; methyltransferase ; molecule ; mutation ; myeloid ; population ; promoter ; protein ; rearrangement ; receptor ; somatic mutation ; syndrome ; tissue ; translocation

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

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. (http://www.ncbi.nlm.nih.gov/pubmed/20018718?dopt=Abstract)
  • Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N. NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. Am J Hum Genet. 2003 Jan;72(1):132-43. Epub 2002 Dec 2. (http://www.ncbi.nlm.nih.gov/pubmed/12464997?dopt=Abstract)
  • Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):24-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16010675?dopt=Abstract)
  • Gene Review: Sotos Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1479)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/11493482?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/24412544?dopt=Abstract)
  • 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. Epub 2002 Mar 18. (http://www.ncbi.nlm.nih.gov/pubmed/11896389?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/20837538?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/64324)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/21972110?dopt=Abstract)
  • 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):8361-8. doi: 10.1074/jbc.M110.204115. Epub 2010 Dec 31. (http://www.ncbi.nlm.nih.gov/pubmed/21196496?dopt=Abstract)
  • 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. Epub 2005 Jun 7. (http://www.ncbi.nlm.nih.gov/pubmed/15942875?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/23592277?dopt=Abstract)
  • 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. Epub 2007 Jun 24. (http://www.ncbi.nlm.nih.gov/pubmed/17589499?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: February 2015
Published: March 30, 2015