FLCN

The FLCN gene provides instructions for making a protein called folliculin. Researchers have not determined the protein's function, but they believe it may act as a tumor suppressor. Tumor suppressors help control the growth and division of cells.

The folliculin protein is present in many of the body's tissues, including the brain, heart, placenta, testis, skin, lung, and kidney. Researchers have proposed several possible roles for the protein within cells. Folliculin may be important for cells' uptake of foreign particles (endocytosis or phagocytosis). The protein may also play a role in the structural framework that helps to define the shape, size, and movement of a cell (the cytoskeleton) and in interactions between cells.

Birt-Hogg-Dubé syndrome - caused by mutations in the FLCN gene

Several mutations in the FLCN gene have been identified in people with Birt-Hogg-Dubé syndrome. Most of these mutations insert or delete one or more protein building blocks (amino acids) in the folliculin protein. These mutations lead to the production of an abnormally small, nonfunctional version of this protein. Without folliculin, researchers believe that cells can grow and divide uncontrollably to form cancerous or noncancerous tumors. They have not determined how a loss of folliculin increases the risk of lung abnormalities that are often associated with Birt-Hogg-Dubé syndrome.

other disorders - caused by mutations in the FLCN gene

At least three mutations in the FLCN gene have been identified in families with a lung condition called spontaneous pneumothorax. A pneumothorax is an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung. Affected individuals tend to have small pockets of air (blebs) in lung tissue that sometimes leak into the chest cavity. These cases are described as spontaneous because they occur in the absence of injury or lung disease. Spontaneous pneumothorax associated with FLCN mutations seems to occur without the other characteristic features of Birt-Hogg-Dubé syndrome (such as skin growths or kidney tumors). It remains unclear how this lung condition results from mutations in the FLCN gene.

other cancers - associated with the FLCN gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, called somatic mutations, are not inherited. Somatic mutations in the FLCN gene are probably associated with several types of nonhereditary (sporadic) tumors. Specifically, somatic FLCN mutations have been identified in some cases of clear cell renal carcinoma (a type of kidney cancer) and in some colon cancers. These mutations may change the structure of the folliculin protein, disrupting its normal function. Researchers do not know how FLCN mutations lead to these particular forms of cancer.