FUS

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.

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.