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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed May 2013

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 whose full range of functions is unknown. This protein is active in many organs and tissues, including the brain, kidneys, skeletal muscle, spleen, thymus (a small gland located behind the breastbone), and lungs. Researchers believe that the NSD1 protein controls the activity of certain genes involved in normal growth and development, and can turn genes on or off as needed.

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? ( 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 100 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 containing 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. It remains unclear how a reduced amount of the NSD1 protein during development leads to overgrowth, learning disabilities, and the other signs and symptoms of Sotos syndrome.

cancers - associated with the NSD1 gene

Changes in the activity of the NSD1 gene are associated with rare cases of a blood cancer called childhood acute myeloid leukemia. Gene activity is disrupted when part of chromosome 5 breaks off and reattaches to part of chromosome 11. This rearrangement of genetic material, called a translocation, abnormally fuses the NSD1 gene on chromosome 5 with the NUP98 gene on chromosome 11. Researchers are investigating how the fused NUP98-NSD1 gene is associated with the development of acute myeloid leukemia.

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.

other disorders - associated with the NSD1 gene

Like Sotos syndrome and Weaver syndrome, Beckwith-Wiedemann syndrome is a genetic condition that involves overgrowth in childhood. Typical signs and symptoms of this disorder include large body size, an enlarged tongue (macroglossia), ear and kidney abnormalities, and an increased risk of certain tumors. It remains controversial whether Beckwith-Wiedemann syndrome can be caused by mutations in the NSD1 gene. A few studies have identified NSD1 mutations in rare cases of this disorder, but other researchers believe that these cases should be classified as unusual presentations of Sotos 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? ( 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
  • nuclear receptor-binding Su-var, Enhancer of zeste and Trithorax domain protein 1
  • SOTOS1

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding NSD1?

acute ; acute myeloid leukemia ; cancer ; chromosome ; disabilities ; DNA ; domain ; enhancer ; gene ; histone ; joint ; kidney ; leukemia ; lysine ; macroglossia ; methyltransferase ; mutation ; myeloid ; population ; protein ; rearrangement ; receptor ; skeletal muscle ; syndrome ; thymus ; translocation

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (


  • Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M, Munnich A, Gicquel C, Cormier-Daire V, Colleaux L. Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. Am J Hum Genet. 2004 Apr;74(4):715-20. Epub 2004 Mar 1. (
  • Cerveira N, Correia C, Dória S, Bizarro S, Rocha P, Gomes P, Torres L, Norton L, Borges BS, Castedo S, Teixeira MR. Frequency of NUP98-NSD1 fusion transcript in childhood acute myeloid leukaemia. Leukemia. 2003 Nov;17(11):2244-7. (
  • 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. (
  • Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):24-31. Review. (
  • Gene Review: Sotos Syndrome (
  • 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. (
  • 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. (
  • NCBI Gene (
  • Niikawa N. Molecular basis of Sotos syndrome. Horm Res. 2004;62 Suppl 3:60-5. Review. (
  • Opitz JM, Weaver DW, Reynolds JF Jr. The syndromes of Sotos and Weaver: reports and review. Am J Med Genet. 1998 Oct 2;79(4):294-304. Review. (
  • 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. (
  • 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. (


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? ( in the Handbook.

Reviewed: May 2013
Published: January 27, 2015