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The '''calcium-sensing receptor''' (CaSR) 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]].<ref name="pmid17117288">{{cite journal | author = D'Souza-Li L | title = The calcium-sensing receptor and related diseases | journal = Arquivos brasileiros de endocrinologia e metabologia | volume = 50 | issue = 4 | pages = 628-39 | year = 2006 | pmid = 17117288 | doi = 10.1590/S0004-27302006000400008 | issn = }}</ref>
The '''calcium-sensing receptor''' (CaSR) 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]].<ref name="pmid17117288">{{cite journal | author = D'Souza-Li L | title = The calcium-sensing receptor and related diseases | journal = Arquivos brasileiros de endocrinologia e metabologia | volume = 50 | issue = 4 | pages = 628–39 | year = 2006 | pmid = 17117288 | doi = 10.1590/S0004-27302006000400008 | issn = }}</ref>


==Pathology==
==Pathology==
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==Therapeutic application==
==Therapeutic application==
The drug [[cinacalcet]] is an [[allosteric]] modifier of the calcium-sensing receptor.<ref name="pmid16825031">{{cite journal | author = Torres PU | title = Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease | journal = Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation | volume = 16 | issue = 3 | pages = 253-8 | year = 2006 | pmid = 16825031 | doi = 10.1053/j.jrn.2006.04.010 | issn = }}</ref>
The drug [[cinacalcet]] is an [[allosteric]] modifier of the calcium-sensing receptor.<ref name="pmid16825031">{{cite journal | author = Torres PU | title = Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease | journal = Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation | volume = 16 | issue = 3 | pages = 253–8 | year = 2006 | pmid = 16825031 | doi = 10.1053/j.jrn.2006.04.010 | issn = }}</ref>


==References==
==References==
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{{PBB_Further_reading
{{PBB_Further_reading
| citations =
| citations =
*{{cite journal | author=Hendy GN, D'Souza-Li L, Yang B, ''et al.'' |title=Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. |journal=Hum. Mutat. |volume=16 |issue= 4 |pages= 281-96 |year= 2000 |pmid= 11013439 |doi= 10.1002/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A }}
*{{cite journal | author=Hendy GN, D'Souza-Li L, Yang B, ''et al.'' |title=Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. |journal=Hum. Mutat. |volume=16 |issue= 4 |pages= 281–96 |year= 2000 |pmid= 11013439 |doi= 10.1002/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A |doilabel=10.1002/1098-1004(200010)16:4&#60;281::AID-HUMU1&#62;3.0.CO;2-A }}
*{{cite journal | author=Fukumoto S |title=[Calcium-sensing receptor in bone cells] |journal=Nippon Rinsho |volume=60 Suppl 3 |issue= |pages= 57-63 |year= 2002 |pmid= 11979955 |doi= }}
*{{cite journal | author=Fukumoto S |title=[Calcium-sensing receptor in bone cells] |journal=Nippon Rinsho |volume=60 Suppl 3 |issue= |pages= 57–63 |year= 2002 |pmid= 11979955 |doi= }}
*{{cite journal | author=Tfelt-Hansen J, Schwarz P, Brown EM, Chattopadhyay N |title=The calcium-sensing receptor in human disease. |journal=Front. Biosci. |volume=8 |issue= |pages= s377-90 |year= 2004 |pmid= 12700051 |doi= }}
*{{cite journal | author=Tfelt-Hansen J, Schwarz P, Brown EM, Chattopadhyay N |title=The calcium-sensing receptor in human disease. |journal=Front. Biosci. |volume=8 |issue= |pages= s377–90 |year= 2004 |pmid= 12700051 |doi= }}
*{{cite journal | author=Hu J, Spiegel AM |title=Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function. |journal=Trends Endocrinol. Metab. |volume=14 |issue= 6 |pages= 282-8 |year= 2004 |pmid= 12890593 |doi= }}
*{{cite journal | author=Hu J, Spiegel AM |title=Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function. |journal=Trends Endocrinol. Metab. |volume=14 |issue= 6 |pages= 282–8 |year= 2004 |pmid= 12890593 |doi= }}
*{{cite journal | author=Aida K, Koishi S, Inoue M, ''et al.'' |title=Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene. |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue= 9 |pages= 2594-8 |year= 1995 |pmid= 7673400 |doi= }}
*{{cite journal | author=Aida K, Koishi S, Inoue M, ''et al.'' |title=Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene. |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue= 9 |pages= 2594–8 |year= 1995 |pmid= 7673400 |doi= }}
*{{cite journal | author=Aida K, Koishi S, Tawata M, Onaya T |title=Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney. |journal=Biochem. Biophys. Res. Commun. |volume=214 |issue= 2 |pages= 524-9 |year= 1995 |pmid= 7677761 |doi= 10.1006/bbrc.1995.2318 }}
*{{cite journal | author=Aida K, Koishi S, Tawata M, Onaya T |title=Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney. |journal=Biochem. Biophys. Res. Commun. |volume=214 |issue= 2 |pages= 524–9 |year= 1995 |pmid= 7677761 |doi= 10.1006/bbrc.1995.2318 }}
*{{cite journal | author=Chou YH, Pollak MR, Brandi ML, ''et al.'' |title=Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia. |journal=Am. J. Hum. Genet. |volume=56 |issue= 5 |pages= 1075-9 |year= 1995 |pmid= 7726161 |doi= }}
*{{cite journal | author=Chou YH, Pollak MR, Brandi ML, ''et al.'' |title=Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia. |journal=Am. J. Hum. Genet. |volume=56 |issue= 5 |pages= 1075–9 |year= 1995 |pmid= 7726161 |doi= }}
*{{cite journal | author=Garrett JE, Capuano IV, Hammerland LG, ''et al.'' |title=Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. |journal=J. Biol. Chem. |volume=270 |issue= 21 |pages= 12919-25 |year= 1995 |pmid= 7759551 |doi= }}
*{{cite journal | author=Garrett JE, Capuano IV, Hammerland LG, ''et al.'' |title=Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. |journal=J. Biol. Chem. |volume=270 |issue= 21 |pages= 12919–25 |year= 1995 |pmid= 7759551 |doi= }}
*{{cite journal | author=Pollak MR, Brown EM, Estep HL, ''et al.'' |title=Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. |journal=Nat. Genet. |volume=8 |issue= 3 |pages= 303-7 |year= 1995 |pmid= 7874174 |doi= 10.1038/ng1194-303 }}
*{{cite journal | author=Pollak MR, Brown EM, Estep HL, ''et al.'' |title=Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. |journal=Nat. Genet. |volume=8 |issue= 3 |pages= 303–7 |year= 1995 |pmid= 7874174 |doi= 10.1038/ng1194-303 }}
*{{cite journal | author=Pollak MR, Brown EM, Chou YH, ''et al.'' |title=Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. |journal=Cell |volume=75 |issue= 7 |pages= 1297-303 |year= 1994 |pmid= 7916660 |doi= }}
*{{cite journal | author=Pollak MR, Brown EM, Chou YH, ''et al.'' |title=Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. |journal=Cell |volume=75 |issue= 7 |pages= 1297–303 |year= 1994 |pmid= 7916660 |doi= }}
*{{cite journal | author=Janicic N, Soliman E, Pausova Z, ''et al.'' |title=Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16. |journal=Mamm. Genome |volume=6 |issue= 11 |pages= 798-801 |year= 1996 |pmid= 8597637 |doi= }}
*{{cite journal | author=Janicic N, Soliman E, Pausova Z, ''et al.'' |title=Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16. |journal=Mamm. Genome |volume=6 |issue= 11 |pages= 798–801 |year= 1996 |pmid= 8597637 |doi= }}
*{{cite journal | author=Bikle DD, Ratnam A, Mauro T, ''et al.'' |title=Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor. |journal=J. Clin. Invest. |volume=97 |issue= 4 |pages= 1085-93 |year= 1996 |pmid= 8613532 |doi= }}
*{{cite journal | author=Bikle DD, Ratnam A, Mauro T, ''et al.'' |title=Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor. |journal=J. Clin. Invest. |volume=97 |issue= 4 |pages= 1085–93 |year= 1996 |pmid= 8613532 |doi= }}
*{{cite journal | author=Pearce SH, Trump D, Wooding C, ''et al.'' |title=Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism. |journal=J. Clin. Invest. |volume=96 |issue= 6 |pages= 2683-92 |year= 1996 |pmid= 8675635 |doi= }}
*{{cite journal | author=Pearce SH, Trump D, Wooding C, ''et al.'' |title=Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism. |journal=J. Clin. Invest. |volume=96 |issue= 6 |pages= 2683–92 |year= 1996 |pmid= 8675635 |doi= }}
*{{cite journal | author=Bai M, Quinn S, Trivedi S, ''et al.'' |title=Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor. |journal=J. Biol. Chem. |volume=271 |issue= 32 |pages= 19537-45 |year= 1996 |pmid= 8702647 |doi= }}
*{{cite journal | author=Bai M, Quinn S, Trivedi S, ''et al.'' |title=Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor. |journal=J. Biol. Chem. |volume=271 |issue= 32 |pages= 19537–45 |year= 1996 |pmid= 8702647 |doi= }}
*{{cite journal | author=Baron J, Winer KK, Yanovski JA, ''et al.'' |title=Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism. |journal=Hum. Mol. Genet. |volume=5 |issue= 5 |pages= 601-6 |year= 1997 |pmid= 8733126 |doi= }}
*{{cite journal | author=Baron J, Winer KK, Yanovski JA, ''et al.'' |title=Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism. |journal=Hum. Mol. Genet. |volume=5 |issue= 5 |pages= 601–6 |year= 1997 |pmid= 8733126 |doi= }}
*{{cite journal | author=Freichel M, Zink-Lorenz A, Holloschi A, ''et al.'' |title=Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. |journal=Endocrinology |volume=137 |issue= 9 |pages= 3842-8 |year= 1996 |pmid= 8756555 |doi= }}
*{{cite journal | author=Freichel M, Zink-Lorenz A, Holloschi A, ''et al.'' |title=Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. |journal=Endocrinology |volume=137 |issue= 9 |pages= 3842–8 |year= 1996 |pmid= 8756555 |doi= }}
*{{cite journal | author=Chattopadhyay N, Ye C, Singh DP, ''et al.'' |title=Expression of extracellular calcium-sensing receptor by human lens epithelial cells. |journal=Biochem. Biophys. Res. Commun. |volume=233 |issue= 3 |pages= 801-5 |year= 1997 |pmid= 9168937 |doi= 10.1006/bbrc.1997.6553 }}
*{{cite journal | author=Chattopadhyay N, Ye C, Singh DP, ''et al.'' |title=Expression of extracellular calcium-sensing receptor by human lens epithelial cells. |journal=Biochem. Biophys. Res. Commun. |volume=233 |issue= 3 |pages= 801–5 |year= 1997 |pmid= 9168937 |doi= 10.1006/bbrc.1997.6553 }}
*{{cite journal | author=Cole DE, Janicic N, Salisbury SR, Hendy GN |title=Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium-sensing receptor gene. |journal=Am. J. Med. Genet. |volume=71 |issue= 2 |pages= 202-10 |year= 1997 |pmid= 9217223 |doi= }}
*{{cite journal | author=Cole DE, Janicic N, Salisbury SR, Hendy GN |title=Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium-sensing receptor gene. |journal=Am. J. Med. Genet. |volume=71 |issue= 2 |pages= 202–10 |year= 1997 |pmid= 9217223 |doi= }}
*{{cite journal | author=Ward BK, Stuckey BG, Gutteridge DH, ''et al.'' |title=A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia. |journal=Hum. Mutat. |volume=10 |issue= 3 |pages= 233-5 |year= 1997 |pmid= 9298824 |doi= 10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J }}
*{{cite journal | author=Ward BK, Stuckey BG, Gutteridge DH, ''et al.'' |title=A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia. |journal=Hum. Mutat. |volume=10 |issue= 3 |pages= 233–5 |year= 1997 |pmid= 9298824 |doi= 10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J |doilabel=10.1002/(SICI)1098-1004(1997)10:3&#60;233::AID-HUMU9&#62;3.0.CO;2-J }}
*{{cite journal | author=Quinn SJ, Kifor O, Trivedi S, ''et al.'' |title=Sodium and ionic strength sensing by the calcium receptor. |journal=J. Biol. Chem. |volume=273 |issue= 31 |pages= 19579-86 |year= 1998 |pmid= 9677383 |doi= }}
*{{cite journal | author=Quinn SJ, Kifor O, Trivedi S, ''et al.'' |title=Sodium and ionic strength sensing by the calcium receptor. |journal=J. Biol. Chem. |volume=273 |issue= 31 |pages= 19579–86 |year= 1998 |pmid= 9677383 |doi= }}
}}
}}
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Revision as of 13:16, 9 June 2008

Template:PBB Controls

CASR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCASR, CAR, EIG8, FHH, FIH, GPRC2A, HHC, HHC1, HYPOC1, NSHPT, PCAR1, calcium sensing receptor, hCasR, Calcium-sensing receptor+CaSR
External IDsOMIM: 601199; MGI: 1351351; HomoloGene: 332; GeneCards: CASR; OMA:CASR - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000388
NM_001178065

NM_013803

RefSeq (protein)

NP_000379
NP_001171536

NP_038831

Location (UCSC)Chr 3: 122.18 – 122.29 MbChr 16: 36.31 – 36.38 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The calcium-sensing receptor (CaSR) 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.[5]

Pathology

Mutations that inactivate CASR cause familial hypocalciuric hypercalcemia (FHH),[6] whereas mutations that activate CASR are the cause of autosomal dominant hypocalcemia.[7] An alternatively spliced transcript variant encoding 1088 aa has been found for this gene, but its full-length nature has not been defined.[8]

Therapeutic application

The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[9]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000036828Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000051980Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ D'Souza-Li L (2006). "The calcium-sensing receptor and related diseases". Arquivos brasileiros de endocrinologia e metabologia. 50 (4): 628–39. doi:10.1590/S0004-27302006000400008. PMID 17117288.
  6. ^ Pidasheva S, Canaff L, Simonds WF, Marx SJ, Hendy GN (2005). "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia". Hum. Mol. Genet. 14 (12): 1679–90. doi:10.1093/hmg/ddi176. PMID 15879434.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Mancilla EE, De Luca F, Baron J (1998). "Activating mutations of the Ca2+-sensing receptor". Mol. Genet. Metab. 64 (3): 198–204. doi:10.1006/mgme.1998.2716. PMID 9719629.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ "Entrez Gene: CASR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)".
  9. ^ Torres PU (2006). "Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease". Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 16 (3): 253–8. doi:10.1053/j.jrn.2006.04.010. PMID 16825031.

Further reading