CDC73

The CDC73 gene (also known as the HRPT2 gene) provides instructions for making a protein called parafibromin. This protein is primarily found in the nucleus of cells and is likely involved in regulating gene transcription, which is the first step in protein production. Parafibromin is also thought to play a role in cell growth and division (proliferation), either promoting or inhibiting cell proliferation depending on signals within the cell. When parafibromin is found outside the nucleus, it appears to be involved in the organization of the cell's structural framework (the cytoskeleton).

familial isolated hyperparathyroidism - caused by mutations in the CDC73 gene

Inherited mutations in the CDC73 gene have been found in some families with familial isolated hyperparathyroidism, a condition characterized by overactivity of the parathyroid glands (primary hyperparathyroidism). These glands release a hormone that helps control the normal balance of calcium in the blood. Primary hyperparathyroidism disrupts this balance, which can lead to high blood calcium levels (hypercalcemia), kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue in people with familial isolated hyperparathyroidism. Primary hyperparathyroidism is a characteristic feature of hyperparathyroidism-jaw tumor syndrome (described below); however, familial isolated hyperparathyroidism is diagnosed in people with hyperparathyroidism but not the other features of hyperparathyroidism-jaw tumor syndrome.

CDC73 gene mutations that cause familial isolated hyperparathyroidism likely result in decreased activity of the parafibromin protein. Reduced parafibromin activity can cause increased cell proliferation, leading to the the formation of tumors involving the parathyroid glands. Parathyroid tumors in people with familial isolated hyperparathyroidism are usually noncancerous. The resulting overactivity of the parathyroid glands causes the signs and symptoms of the condition. The mutations associated with familial isolated hyperparathyroidism are thought to have a less severe effect on protein function than those that cause hyperparathyroidism-jaw tumor syndrome. Occasionally, individuals with familial isolated hyperparathyroidism later develop features of hyperparathyroidism-jaw tumor syndrome, although some never do. Familial isolated hyperparathyroidism caused by CDC73 gene mutations may be an early or mild form of hyperparathyroidism-jaw tumor syndrome.

hyperparathyroidism-jaw tumor syndrome - caused by mutations in the CDC73 gene

More than 40 mutations in the CDC73 gene have been found to cause hyperparathyroidism-jaw tumor syndrome. Most of these mutations result in a parafibromin protein that is abnormally short and nonfunctional. Without functional parafibromin, cell proliferation is not properly regulated. Uncontrolled cell division resulting from the loss of parafibromin function can lead to the formation of tumors in the parathyroid glands, jaw, uterus, and kidneys in people with hyperparathyroidism-jaw tumor syndrome. Parathyroid tumors, which can be cancerous or noncancerous, interfere with the gland's normal function and lead to primary hyperparathyroidism, a characteristic feature of hyperparathyroidism-jaw tumor syndrome.

cancers - associated with the CDC73 gene

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 changes in the CDC73 gene have been identified in many parathyroid cancers. These mutations prevent parafibromin from effectively regulating cell proliferation, leading to uncontrolled cell growth and tumor development. It is unclear why these mutations are associated with cancer in the parathyroid glands but not in other tissues in the body.