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Genetics Home Reference: your guide to understanding genetic conditions
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FUS

Reviewed August 2012

What is the official name of the FUS gene?

The official name of this gene is “FUS RNA binding protein.”

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

What is the normal function of the FUS gene?

The FUS gene provides instructions for making a protein called fused in sarcoma (FUS). This protein is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. The FUS protein attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. This protein also helps repair mistakes in DNA, which prevents cells from accumulating genetic damage.

The FUS protein is also involved in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the FUS protein controls the production of different versions of certain proteins. This process is known as alternative splicing. Once the FUS protein processes the mRNA, it transports the mRNA out of the nucleus where it gets taken up by other cell structures to be further processed into a mature protein.

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

amyotrophic lateral sclerosis - caused by mutations in the FUS gene

At least 50 mutations in the FUS gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. Most of these mutations change single protein building blocks in the FUS protein. The majority of these changes affect the region of the protein involved in DNA binding and mRNA processing. These mutations may interfere with the transport of mRNA out of the nucleus of cells, particularly nerve cells that control muscle movement. A disruption in mRNA transport is likely to cause the FUS protein clumps (aggregates) within nerve cells that are observed in some people with ALS. It is unclear whether a buildup of protein aggregates causes nerve cell death and leads to ALS. People with ALS caused by mutations in the FUS gene tend to develop the disease earlier and have a decreased life expectancy compared with individuals who have ALS caused by mutations in other genes.

Some people with ALS caused by FUS gene mutations also develop a condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. It is unclear why some people with FUS gene mutations develop FTD and others do not. Individuals who develop both conditions are diagnosed as having ALS-FTD.

cancers - associated with the FUS gene

Specific mutations involving the FUS gene are involved in several types of cancer. Most commonly, mutations in this gene are found in tumors called soft tissue sarcomas, which develop in bones or in soft tissues such as nerves or cartilage. FUS gene mutations have also been found in myxoid liposarcomas, which occur in fatty tissues of the body, or cancer of the blood-forming cells in the bone marrow called acute myeloid leukemia (AML). The genetic changes associated with these cancers are rearrangements (translocations) of genetic material between chromosome 16 (where the FUS gene is located) and other chromosomes. These translocations break chromosome 16 in the middle of the FUS gene and fuse it with another gene on a different chromosome, creating a fusion gene. Fusion genes usually have partial function of both genes involved. The FUS gene promotes DNA transcription and protein production, which helps promote cell growth; this gene might fuse with another gene that could allow cell growth to continue at a rapid pace. When cell growth is left uncontrolled, tumors can develop. The mutations that cause these tumors are acquired during a person's lifetime and are present only in the tumor cells. This type of genetic change, called a somatic mutation, is not inherited.

Where is the FUS gene located?

Cytogenetic Location: 16p11.2

Molecular Location on chromosome 16: base pairs 31,180,109 to 31,194,870

The FUS gene is located on the short (p) arm of chromosome 16 at position 11.2.

The FUS gene is located on the short (p) arm of chromosome 16 at position 11.2.

More precisely, the FUS gene is located from base pair 31,180,109 to base pair 31,194,870 on chromosome 16.

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 FUS?

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

  • ALS6
  • FUS1
  • fused in sarcoma
  • FUS_HUMAN
  • heterogeneous nuclear ribonucleoprotein P2
  • HNRNPP2
  • hnRNP-P2
  • oncogene FUS
  • oncogene TLS
  • POMP75
  • RNA-binding protein FUS
  • TLS
  • translocated in liposarcoma protein

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 FUS?

acute ; acute myeloid leukemia ; alternative splicing ; AML ; bone marrow ; cancer ; cartilage ; cell ; cell nucleus ; chromosome ; dementia ; DNA ; fusion gene ; gene ; leukemia ; messenger RNA ; mRNA ; mutation ; myeloid ; nerve cell ; nucleus ; oncogene ; protein ; RNA ; sarcoma ; sclerosis ; soft tissue ; somatic mutation ; splicing ; tissue ; transcription ; tumor ; wasting

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

References

  • Budini M, Baralle FE, Buratti E. Regulation of gene expression by TDP-43 and FUS/TLS in frontotemporal lobar degeneration. Curr Alzheimer Res. 2011 May;8(3):237-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21222602?dopt=Abstract)
  • Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993 Jun 17;363(6430):640-4. (http://www.ncbi.nlm.nih.gov/pubmed/8510758?dopt=Abstract)
  • Ferraiuolo L, Kirby J, Grierson AJ, Sendtner M, Shaw PJ. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat Rev Neurol. 2011 Nov;7(11):616-30. doi: 10.1038/nrneurol.2011.152. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22051914?dopt=Abstract)
  • Hewitt C, Kirby J, Highley JR, Hartley JA, Hibberd R, Hollinger HC, Williams TL, Ince PG, McDermott CJ, Shaw PJ. Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol. 2010 Apr;67(4):455-61. doi: 10.1001/archneurol.2010.52. (http://www.ncbi.nlm.nih.gov/pubmed/20385912?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2521)
  • OMIM: FUSED IN SARCOMA (http://omim.org/entry/137070)
  • Panagopoulos I, Storlazzi CT, Fletcher CD, Fletcher JA, Nascimento A, Domanski HA, Wejde J, Brosjö O, Rydholm A, Isaksson M, Mandahl N, Mertens F. The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma. Genes Chromosomes Cancer. 2004 Jul;40(3):218-28. (http://www.ncbi.nlm.nih.gov/pubmed/15139001?dopt=Abstract)
  • Storlazzi CT, Mertens F, Nascimento A, Isaksson M, Wejde J, Brosjo O, Mandahl N, Panagopoulos I. Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma. Hum Mol Genet. 2003 Sep 15;12(18):2349-58. Epub 2003 Jul 22. (http://www.ncbi.nlm.nih.gov/pubmed/12915480?dopt=Abstract)
  • Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009 Feb 27;323(5918):1208-11. doi: 10.1126/science.1165942. (http://www.ncbi.nlm.nih.gov/pubmed/19251628?dopt=Abstract)
  • Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008 Jul 3;454(7200):126-30. doi: 10.1038/nature06992. Epub 2008 May 28. (http://www.ncbi.nlm.nih.gov/pubmed/18509338?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: August 2012
Published: July 7, 2014