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

CASR gene

calcium sensing receptor

Normal Function

The CASR gene provides instructions for making a protein called the calcium-sensing receptor (CaSR). Calcium molecules bind to CaSR, which allows this protein to monitor and regulate the amount of calcium in the blood.

The CaSR protein is found in cells of the parathyroid glands. The four parathyroid glands are located in the neck. These glands produce and release a hormone called parathyroid hormone, which regulates the levels of calcium in the blood. When blood calcium levels are high, calcium binds to CaSR in the parathyroid glands and blocks the production of parathyroid hormone. Without parathyroid hormone, calcium is not released into the blood. CaSR signaling also blocks the growth and division (proliferation) of the cells that make up the parathyroid glands.

The CaSR protein is also found in kidney cells. Kidneys filter fluid and waste products in the body and can reabsorb needed nutrients and release them back into the blood. When calcium binds to CaSR in kidney cells, it blocks the reabsorption of calcium and allows it to be released in the urine.

Health Conditions Related to Genetic Changes

Autosomal dominant hypocalcemia

Variants (also called mutations) in the CASR gene can cause a condition called autosomal dominant hypocalcemia, which is characterized by low levels of calcium in the blood (hypocalcemia). Some affected individuals also have a shortage of parathyroid hormone (hypoparathyroidism). When this condition is caused by CASR gene variants, it is known as autosomal dominant hypocalcemia type 1.

Most of the CASR gene variants that cause autosomal dominant hypocalcemia type 1 lead to the substitution of one protein building block (amino acid) for another in the CaSR protein. This causes cells to produce an overactive version of the CaSR protein that is more sensitive to calcium, meaning low levels of calcium can trigger signaling. The overactive CaSR protein blocks the release of parathyroid hormone and prevents the release of calcium into the blood when it is needed. In addition, the overactive CaSR protein prevents reabsorption of calcium from the fluids that are filtered through the kidneys. As a result, there is not enough calcium in the bloodstream. Hypocalcemia can cause muscle cramping and seizures, although about half of people with autosomal dominant hypocalcemia type 1 have no associated health problems.

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Familial isolated hyperparathyroidism

Variants in the CASR 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 blood calcium levels (hypercalcemia), kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue.

The CASR gene variants that cause familial isolated hyperparathyroidism lead to the substitution of one amino acid for another in the CaSR protein. This causes cells to produce an altered version of the CaSR protein that is less sensitive to calcium and requires higher levels of calcium to trigger signaling. As a result, parathyroid hormone is produced even when calcium in the blood is elevated, allowing the calcium levels to continue to rise. In addition, parathyroid cells may proliferate in an uncontrolled way, which causes enlargement (hyperplasia) of the parathyroid glands in people with familial isolated hyperparathyroidism. The overproduction of parathyroid hormone from these abnormal glands may further stimulate the release of calcium into the blood. The high levels of calcium cause the signs and symptoms of familial isolated hyperparathyroidism.

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Kidney stones

MedlinePlus Genetics provides information about Kidney stones

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Other disorders

Variants in the CASR gene are involved in several other conditions that are associated with abnormal calcium levels.

Variants that cause cells to produce a version of the CaSR protein that does not function properly can cause familial hypocalciuric hypercalcemia. This condition is characterized by hypercalcemia and low levels of calcium in the urine (hypocalciuria), but affected individuals typically have no symptoms related to the condition. Rarely, affected individuals have enlarged parathyroid glands and slightly elevated levels of parathyroid hormone.

A condition called neonatal severe hyperparathyroidism is caused by CASR gene variants that severely impact the function of the CaSR protein. Neonatal severe hyperparathyroidism is a potentially fatal condition that begins before the age of 6 months. Affected babies often have parathyroid hyperplasia, which causes high levels of parathyroid hormone in their blood. The excess hormone stimulates the release of calcium into the blood, causing hypercalcemia. The calcium released into the blood is often removed from bone, resulting in skeletal abnormalities. The extreme hypercalcemia in these individuals can lead to neurological problems because the excess calcium interferes with nerve signaling.

Other Names for This Gene

  • calcium-sensing receptor
  • CAR
  • extracellular calcium-sensing receptor
  • GPRC2A
  • parathyroid Ca(2+)-sensing receptor 1
  • parathyroid cell calcium-sensing receptor
  • PCAR1

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

  • Cetani F, Pardi E, Aretini P, Saponaro F, Borsari S, Mazoni L, Apicella M, Civita P, La Ferla M, Caligo MA, Lessi F, Mazzanti CM, Torregossa L, Oppo A, Marcocci C. Whole exome sequencing in familial isolated primary hyperparathyroidism. J Endocrinol Invest. 2020 Feb;43(2):231-245. doi: 10.1007/s40618-019-01107-5. Epub 2019 Sep 5. Citation on PubMed
  • Charoenngam N, Wattanachayakul P, Mannstadt M. CASRdb: A Publicly Accessible Comprehensive Database for Disease-Associated Calcium-Sensing Receptor Variants. J Clin Endocrinol Metab. 2025 Jan 21;110(2):297-302. doi: 10.1210/clinem/dgae769. Citation on PubMed
  • English KA, Lines KE, Thakker RV. Genetics of hereditary forms of primary hyperparathyroidism. Hormones (Athens). 2024 Mar;23(1):3-14. doi: 10.1007/s42000-023-00508-9. Epub 2023 Dec 1. Citation on PubMed
  • Hannan FM, Nesbit MA, Christie PT, Lissens W, Van der Schueren B, Bex M, Bouillon R, Thakker RV. A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia. Clin Endocrinol (Oxf). 2010 Dec;73(6):715-22. doi: 10.1111/j.1365-2265.2010.03870.x. Citation on PubMed
  • Hendy GN, Guarnieri V, Canaff L. Calcium-sensing receptor and associated diseases. Prog Mol Biol Transl Sci. 2009;89:31-95. doi: 10.1016/S1877-1173(09)89003-0. Epub 2009 Oct 7. Citation on PubMed
  • Kinoshita Y, Hori M, Taguchi M, Watanabe S, Fukumoto S. Functional activities of mutant calcium-sensing receptors determine clinical presentations in patients with autosomal dominant hypocalcemia. J Clin Endocrinol Metab. 2014 Feb;99(2):E363-8. doi: 10.1210/jc.2013-3430. Epub 2013 Dec 2. Citation on PubMed
  • Ranieri M, Tamma G, Di Mise A, Vezzoli G, Soldati L, Svelto M, Valenti G. Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR) are associated with increased ER to cytosol calcium gradient. PLoS One. 2013 Nov 14;8(11):e79113. doi: 10.1371/journal.pone.0079113. eCollection 2013. Citation on PubMed or Free article on PubMed Central
  • Raue F, Pichl J, Dorr HG, Schnabel D, Heidemann P, Hammersen G, Jaursch-Hancke C, Santen R, Schofl C, Wabitsch M, Haag C, Schulze E, Frank-Raue K. Activating mutations in the calcium-sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia - a German survey. Clin Endocrinol (Oxf). 2011 Dec;75(6):760-5. doi: 10.1111/j.1365-2265.2011.04142.x. Citation on PubMed
  • Thim SB, Birkebaek NH, Nissen PH, Host C. Activating calcium-sensing receptor gene variants in children: a case study of infant hypocalcaemia and literature review. Acta Paediatr. 2014 Nov;103(11):1117-25. doi: 10.1111/apa.12743. Epub 2014 Aug 24. Citation on PubMed
  • Warner J, Epstein M, Sweet A, Singh D, Burgess J, Stranks S, Hill P, Perry-Keene D, Learoyd D, Robinson B, Birdsey P, Mackenzie E, Teh BT, Prins JB, Cardinal J. Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 2004 Mar;41(3):155-60. doi: 10.1136/jmg.2003.016725. Citation on PubMed or Free article on PubMed Central

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