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CDC73 gene
URL of this page: https://medlineplus.gov/genetics/gene/cdc73/

CDC73 gene

cell division cycle 73

Normal Function

The CDC73 gene provides instructions for making a protein called parafibromin. This protein is found primarily in the nucleus of cells and is likely involved in regulating gene transcription, which is the first step in protein production. Parafibromin functions as a tumor suppressor, which means it keeps cells from growing and dividing (proliferating) too fast or in an uncontrolled way. When parafibromin is found outside the nucleus, it appears to be involved in the organization of the cell's structural framework (the cytoskeleton).

Health Conditions Related to Genetic Changes

Familial isolated hyperparathyroidism

Variants (also called mutations) in the CDC73 gene have been found in some people with familial isolated hyperparathyroidism, a condition that is characterized by overactive parathyroid glands (hyperparathyroidism). These four glands are located in the neck and release a hormone that helps regulate the levels of calcium in the blood. This regulation is disrupted in people with familial isolated hyperparathyroidism, which can lead to high levels of calcium in the blood (hypercalcemia), kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue.

The CDC73 gene variants that cause familial isolated hyperparathyroidism reduce the activity of the parafibromin protein. This can increase cell proliferation, causing one or more of the parathyroid glands to become enlarged (hyperplasia) or to develop a tumor. Parathyroid tumors in people with familial isolated hyperparathyroidism are usually noncancerous (benign) tumors called adenomas. The adenomas or enlarged parathyroid glands stimulate the overproduction of parathyroid hormone, which triggers the release of calcium into the blood. This excess calcium causes the characteristic features of familial isolated hyperparathyroidism.

The CDC73 gene variants that are associated with familial isolated hyperparathyroidism are thought to have a less severe effect on protein function than those that cause hyperparathyroidism-jaw tumor syndrome (described below). Occasionally, individuals with familial isolated hyperparathyroidism develop features of hyperparathyroidism-jaw tumor syndrome. The cases of familial isolated hyperparathyroidism that are caused by CDC73 gene variants may be an early or mild form of hyperparathyroidism-jaw tumor syndrome.

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Hyperparathyroidism-jaw tumor syndrome

Variants in the CDC73 gene have been found to cause hyperparathyroidism-jaw tumor syndrome, which is a condition that is characterized by parathyroid tumors that cause hyperparathyroidism. People with this condition have an increased risk of benign tumors in the jaw, kidneys, and uterus. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, osteoporosis, nausea, vomiting, hypertension, weakness, and fatigue in people with hyperparathyroidism-jaw tumor syndrome.

Most of the CDC73 gene variants that are associated with this condition cause cells to produce a version of the parafibromin protein that is abnormally short and does not function properly. Without functional parafibromin, cell proliferation is not properly regulated. Uncontrolled cell division can cause tumors to form in the parathyroid glands. When the tumors interfere with the normal functions of the glands, hyperparathyroidism can occur in people with hyperparathyroidism-jaw tumor syndrome.

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Parathyroid cancer

Variants in the CDC73 gene are found in up to 70 percent of people with parathyroid cancer. Of these individuals, approximately one-third inherit the variant from a parent, and the variant is present in all of the body's cells (germline variant). In the remaining two-thirds of individuals, the CDC73 gene variant occurs in parathyroid cells during the person's lifetime (somatic variant). However, not everyone who has a variant in the CDC73 gene will ultimately develop parathyroid cancer. Other genetic and nongenetic factors also contribute to a person's cancer risk.

A variant must occur in both copies of the CDC73 gene for parathyroid cancer to develop. Parathyroid cells with two altered copies of the CDC73 gene produce no functional parafibromin. As a result, the cells grow and divide unchecked, which can lead to parathyroid cancer.

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Other Names for This Gene

  • C1orf28
  • CDC73_HUMAN
  • cell division cycle protein 73 homolog
  • HRPT2
  • hyperparathyroidism 2 protein
  • hyrax
  • HYX
  • parafibromin

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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