Calcium Sensing Receptor (CASR)

CAR; FHH; FIH; GPRC2A; HHC; HHC1; NSHPT; PCAR1; Parathyroid cell calcium-sensing receptor 1; Hypocalciuric Hypercalcemia 1; Severe Neonatal Hyperparathyroidism

SPN	U434
HGNC	1514
MGI	1351351
PubMed	20164288
RGD	2277
UniProt	P41180
Wiki	CaSR

Extracellular calcium-sensing receptor is a G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH).

Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia (FHH) (also known as Familial Benign Hypercalcemia because it is generally asymptomatic and does not require treatment), whereas mutations that activate CASR are the cause of autosomal dominant hypocalcemia. An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.

Reference

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"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

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"Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor."
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"Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin."
J. Biol. Chem. 281:11610-11617(2006) [PubMed] [Europe PMC] [Abstract]

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Endocrinology 151:5114-5123(2010) [PubMed] [Europe PMC] [Abstract]

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"The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism."
Hum. Genet. 98:129-133(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism."
Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract]

"A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor."
N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract]

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"Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor."
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"Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism."
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"Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor."
J. Clin. Endocrinol. Metab. 83:2497-2502(1998) [PubMed] [Europe PMC] [Abstract]

"An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium-sensing receptor."
Clin. Endocrinol. (Oxf.) 50:537-543(1999) [PubMed] [Europe PMC] [Abstract]

"A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia."
J. Clin. Endocrinol. Metab. 84:363-366(1999) [PubMed] [Europe PMC] [Abstract]

"Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis."
J. Clin. Endocrinol. Metab. 84:3036-3040(1999) [PubMed] [Europe PMC] [Abstract]

"A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations."
Lancet 353:112-115(1999) [PubMed] [Europe PMC] [Abstract]

"Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor."
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"A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia."
Endocrine 15:277-282(2001) [PubMed] [Europe PMC] [Abstract]

"Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene."
Mol. Genet. Metab. 72:168-174(2001) [PubMed] [Europe PMC] [Abstract]

"A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor."
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"Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene."
J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract]

"Association between activating mutations of calcium-sensing receptor and Bartter's syndrome."
Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract]

"Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor."
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"Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene."
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"Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor."
J. Clin. Endocrinol. Metab. 89:5634-5638(2004) [PubMed] [Europe PMC] [Abstract]

"Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor."
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"Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications."
J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract]

"A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia."
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"Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia."
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"Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism."
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"Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor."
Biochem. Biophys. Res. Commun. 342:996-1002(2006) [PubMed] [Europe PMC] [Abstract]

"A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone."
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"Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status."
J. Clin. Endocrinol. Metab. 92:2616-2623(2007) [PubMed] [Europe PMC] [Abstract]

"Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population."
J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract]

"An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene."
Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract]

"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.) 73:715-722(2010) [PubMed] [Europe PMC] [Abstract]

"Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine."
Eur. J. Pediatr. 171:147-150(2012) [PubMed] [Europe PMC] [Abstract]