MEN1

The MEN1 gene provides instructions for making a protein called menin. This protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. Although the exact function of menin is uncertain, it is likely involved in several important cell functions. For example, it may play a role in copying and repairing DNA and regulating controlled cell death (apoptosis). The menin protein is present in the nucleus of many different types of cells and appears to be active in all stages of development.

Menin interacts with many other proteins, including several transcription factors. Transcription factors bind to specific areas of DNA and help control whether particular genes are turned on or off. Some of these genes likely play a role in cell growth and division. Researchers are working to identify the proteins that interact with menin and determine its specific role as a tumor suppressor.

multiple endocrine neoplasia - caused by mutations in the MEN1 gene

More than 400 mutations in the MEN1 gene can cause multiple endocrine neoplasia type 1. Most of these mutations lead to the production of an abnormally short, inactive version of menin or an unstable protein that rapidly breaks down. As a result of these mutations, one copy of the MEN1 gene in each cell makes no functional protein. If the second copy of the MEN1 gene is also altered in certain cells, those cells have no working copies of the gene and do not produce any menin. Without this protein, cells in endocrine glands and other tissues can divide too frequently and form tumors. Although menin appears to be necessary for preventing tumor formation, researchers have not determined how a lack of this protein leads to the particular tumors characteristic of multiple endocrine neoplasia type 1.

other disorders - associated with the MEN1 gene

Mutations in the MEN1 gene have been found in some cases of familial isolated hyperparathyroidism (FIHP), a condition characterized by overactivity of the parathyroid gland. Hyperparathyroidism is the most common sign of multiple endocrine neoplasia type 1; however, the isolated form occurs in families without the other features of that disorder. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue. It remains unclear whether familial isolated hyperparathyroidism is a variant form of multiple endocrine neoplasia type 1 or a separate disorder.

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the MEN1 gene have been identified in several types of nonhereditary (sporadic) tumors. Specifically, MEN1 mutations have been found in a significant percentage of noncancerous tumors of the parathyroid gland (parathyroid adenomas), pancreatic tumors called gastrinomas and insulinomas, and cancerous tumors of the major airways in the lungs (bronchi) called bronchial carcinoids. Many of these tumor types are also found in people who have multiple endocrine neoplasia type 1. Like hereditary MEN1 mutations, somatic mutations in the MEN1 gene allow the formation of tumors when both copies of the MEN1 gene are inactivated in select cells.