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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 (formerly known as HRPT2) 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 rapidly 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 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 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. Reduced parafibromin activity can increase cell proliferation, leading to the formation of tumors in the parathyroid glands. Parathyroid tumors in people with familial isolated hyperparathyroidism are usually noncancerous (benign). The tumors cause the glands to be overactive, resulting in primary hyperparathyroidism. 

The variants 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, although some never do. Familial isolated hyperparathyroidism caused by CDC73 gene variants may be an early or mild form of hyperparathyroidism-jaw tumor syndrome.

More About This Health Condition

Hyperparathyroidism-jaw tumor syndrome

Variants in the CDC73 gene have been found to cause hyperparathyroidism-jaw tumor syndrome, which is a condition characterized by parathyroid tumors that cause hyperparathyroidism. People with this condition also have an increased risk of other 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 cause this condition can cause the cell 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 lead to the formation of tumors in people with hyperparathyroidism-jaw tumor syndrome. Parathyroid tumors, which can be benign or cancerous, interfere with the gland's normal function and lead to hyperparathyroidism 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 mutation). In the remaining two-thirds of individuals, the CDC73 gene variant occurs in parathyroid cells during the person's lifetime (somatic mutation). 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.

In individuals with either a germline or somatic CDC73 gene variant, a second variant in the other copy of the CDC73 gene must occur 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.

A significantly increased risk of parathyroid cancer is a feature of hyperparathyroidism-jaw tumor syndrome and familial isolated hyperparathyroidism (both described above). Parathyroid cancer occurs in 15 percent of individuals with hyperparathyroidism-jaw tumor syndrome and in 1 percent of individuals with familial isolated hyperparathyroidism. It is unclear why some people with a CDC73 gene variant will develop isolated parathyroid cancer while others will develop noncancerous tumors in the parathyroid glands and jaw or, hyperparathyroidism.

More About This Health Condition

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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  • Cetani F, Pardi E, Marcocci C. Update on parathyroid carcinoma. J Endocrinol Invest. 2016 Jun;39(6):595-606. doi: 10.1007/s40618-016-0447-3. Epub 2016 Mar 21. Citation on PubMed
  • Fernandez-Ranvier GG, Khanafshar E, Tacha D, Wong M, Kebebew E, Duh QY, Clark OH. Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer. 2009 Jan 15;115(2):334-44. doi: 10.1002/cncr.24037. Citation on PubMed
  • Figueiredo AA, Saramago A, Cavaco BM, Simoes-Pereira J, Leite V. Familial parathyroid tumours-comparison of clinical profiles between syndromes. J Endocrinol Invest. 2023 Sep;46(9):1799-1806. doi: 10.1007/s40618-023-02032-4. Epub 2023 Feb 13. Citation on PubMed
  • Masi G, Barzon L, Iacobone M, Viel G, Porzionato A, Macchi V, De Caro R, Favia G, Palu G. Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer. 2008 Dec;15(4):1115-26. doi: 10.1677/ERC-08-0066. Epub 2008 Aug 28. Citation on PubMed
  • Newey PJ, Bowl MR, Cranston T, Thakker RV. Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors. Hum Mutat. 2010 Mar;31(3):295-307. doi: 10.1002/humu.21188. Citation on PubMed
  • Newey PJ, Bowl MR, Thakker RV. Parafibromin--functional insights. J Intern Med. 2009 Jul;266(1):84-98. doi: 10.1111/j.1365-2796.2009.02107.x. Citation on PubMed
  • Serrano-Gonzalez M, Shay S, Austin J, Maceri DR, Pitukcheewanont P. A germline mutation of HRPT2/CDC73 (70 G>T) in an adolescent female with parathyroid carcinoma: first case report and a review of the literature. J Pediatr Endocrinol Metab. 2016 Sep 1;29(9):1005-12. doi: 10.1515/jpem-2016-0109. Citation on PubMed
  • Tora R, Welch J, Sun J, Agarwal SK, Bell DA, Merino M, Weinstein LS, Simonds WF, Jha S. Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3165-3177. doi: 10.1210/clinem/dgad368. Citation on PubMed
  • Torresan F, Iacobone M. Clinical Features, Treatment, and Surveillance of Hyperparathyroidism-Jaw Tumor Syndrome: An Up-to-Date and Review of the Literature. Int J Endocrinol. 2019 Dec 18;2019:1761030. doi: 10.1155/2019/1761030. eCollection 2019. Citation on PubMed
  • van der Tuin K, Tops CMJ, Adank MA, Cobben JM, Hamdy NAT, Jongmans MC, Menko FH, van Nesselrooij BPM, Netea-Maier RT, Oosterwijk JC, Valk GD, Wolffenbuttel BHR, Hes FJ, Morreau H. CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4534-4540. doi: 10.1210/jc.2017-01249. Citation on PubMed
  • Villablanca A, Calender A, Forsberg L, Hoog A, Cheng JD, Petillo D, Bauters C, Kahnoski K, Ebeling T, Salmela P, Richardson AL, Delbridge L, Meyrier A, Proye C, Carpten JD, Teh BT, Robinson BG, Larsson C. Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet. 2004 Mar;41(3):e32. doi: 10.1136/jmg.2003.012369. No abstract available. Citation on PubMed or Free article on PubMed Central
  • Wang PF, Tan MH, Zhang C, Morreau H, Teh BT. HRPT2, a tumor suppressor gene for hyperparathyroidism-jaw tumor syndrome. Horm Metab Res. 2005 Jun;37(6):380-3. doi: 10.1055/s-2005-870150. Citation on PubMed
  • Westin G. Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours. J Intern Med. 2016 Dec;280(6):551-558. doi: 10.1111/joim.12458. Epub 2016 Apr 12. Citation on PubMed

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