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Calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)
External IDs OMIM601199 MGI1351351 HomoloGene332 IUPHAR: CaS GeneCards: CASR Gene
RNA expression pattern
PBB GE CASR 210577 at tn.png
PBB GE CASR 211384 s at tn.png
More reference expression data
Species Human Mouse
Entrez 846 12374
Ensembl ENSG00000036828 ENSMUSG00000051980
UniProt P41180 O88982
RefSeq (mRNA) NM_000388 NM_013803
RefSeq (protein) NP_000379 NP_038831
Location (UCSC) Chr 3:
123.39 - 123.49 Mb
Chr 16:
36.41 - 36.48 Mb
PubMed search [1] [2]

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 (PTH).[1]


Signal transduction

The release of PTH is inhibited in response to elevations in plasma calcium concentrations and activation of the calcium receptor. Decreased calcium binding on the extracellular side gives a conformation change in the receptor, which, on the intracellular side, initiates the phospholipase C pathway,[2][3] presumably through a G type of G protein, which ultimately increases intracellular concentration of calcium, which triggers vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some[4] sources state) the cAMP dependent pathway.[3]


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

Therapeutic application

The drug cinacalcet is an allosteric modifier of the calcium-sensing receptor.[8] It is classified as a calcimimetic, which binds to the calcium-sensing receptor and decreases parathyroid hormone release.


Calcium-sensing receptor has been shown to interact with Filamin.[9][10]


  1. ^ 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.  
  2. ^ InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved on June 2, 2009
  3. ^ a b Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (December 1999). "Calcium-sensing receptor and calcimimetic agents". Kidney Int. Suppl. 73: S52–8. PMID 10633465.  
  4. ^ Costanzo, Linda S. (2007). BRS Physiology. Lippincott, Williams, & Wilkins. pp. 260. ISBN 978-0781773119.  
  5. ^ 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.  
  6. ^ 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.  
  7. ^ "Entrez Gene: CASR calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)".  
  8. ^ 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.  
  9. ^ Hjälm, G; MacLeod R J, Kifor O, Chattopadhyay N, Brown E M (Sep. 2001). "Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase". J. Biol. Chem. (United States) 276 (37): 34880–7. doi:10.1074/jbc.M100784200. ISSN 0021-9258. PMID 11390380.  
  10. ^ Awata, H; Huang C, Handlogten M E, Miller R T (Sep. 2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". J. Biol. Chem. (United States) 276 (37): 34871–9. doi:10.1074/jbc.M100775200. ISSN 0021-9258. PMID 11390379.  

Further reading

  • Hendy GN, D'Souza-Li L, Yang B, et al. (2000). "Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.". Hum. Mutat. 16 (4): 281–96. doi:10.1002/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A. PMID 11013439.  
  • Fukumoto S (2002). "[Calcium-sensing receptor in bone cells]". Nippon Rinsho 60 Suppl 3: 57–63. PMID 11979955.  
  • Tfelt-Hansen J, Schwarz P, Brown EM, Chattopadhyay N (2004). "The calcium-sensing receptor in human disease.". Front. Biosci. 8: s377–90. doi:10.2741/1068. PMID 12700051.  
  • Hu J, Spiegel AM (2004). "Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function.". Trends Endocrinol. Metab. 14 (6): 282–8. PMID 12890593.  
  • Aida K, Koishi S, Inoue M, et al. (1995). "Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene.". J. Clin. Endocrinol. Metab. 80 (9): 2594–8. doi:10.1210/jc.80.9.2594. PMID 7673400.  
  • Aida K, Koishi S, Tawata M, Onaya T (1995). "Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney.". Biochem. Biophys. Res. Commun. 214 (2): 524–9. doi:10.1006/bbrc.1995.2318. PMID 7677761.  
  • Chou YH, Pollak MR, Brandi ML, et al. (1995). "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.". Am. J. Hum. Genet. 56 (5): 1075–9. PMID 7726161.  
  • Garrett JE, Capuano IV, Hammerland LG, et al. (1995). "Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs.". J. Biol. Chem. 270 (21): 12919–25. doi:10.1074/jbc.270.21.12919. PMID 7759551.  
  • Pollak MR, Brown EM, Estep HL, et al. (1995). "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation.". Nat. Genet. 8 (3): 303–7. doi:10.1038/ng1194-303. PMID 7874174.  
  • Pollak MR, Brown EM, Chou YH, et al. (1994). "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.". Cell 75 (7): 1297–303. doi:10.1016/0092-8674(93)90617-Y. PMID 7916660.  
  • Janicic N, Soliman E, Pausova Z, et al. (1996). "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.". Mamm. Genome 6 (11): 798–801. doi:10.1007/BF00539007. PMID 8597637.  
  • Bikle DD, Ratnam A, Mauro T, et al. (1996). "Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor.". J. Clin. Invest. 97 (4): 1085–93. doi:10.1172/JCI118501. PMID 8613532.  
  • Pearce SH, Trump D, Wooding C, et al. (1996). "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.". J. Clin. Invest. 96 (6): 2683–92. doi:10.1172/JCI118335. PMID 8675635.  
  • Bai M, Quinn S, Trivedi S, et al. (1996). "Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor.". J. Biol. Chem. 271 (32): 19537–45. doi:10.1074/jbc.271.32.19537. PMID 8702647.  
  • Baron J, Winer KK, Yanovski JA, et al. (1997). "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism.". Hum. Mol. Genet. 5 (5): 601–6. doi:10.1093/hmg/5.5.601. PMID 8733126.  
  • Freichel M, Zink-Lorenz A, Holloschi A, et al. (1996). "Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion.". Endocrinology 137 (9): 3842–8. doi:10.1210/en.137.9.3842. PMID 8756555.  
  • Chattopadhyay N, Ye C, Singh DP, et al. (1997). "Expression of extracellular calcium-sensing receptor by human lens epithelial cells.". Biochem. Biophys. Res. Commun. 233 (3): 801–5. doi:10.1006/bbrc.1997.6553. PMID 9168937.  
  • Cole DE, Janicic N, Salisbury SR, Hendy GN (1997). "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.". Am. J. Med. Genet. 71 (2): 202–10. doi:10.1002/(SICI)1096-8628(19970808)71:2<202::AID-AJMG16>3.0.CO;2-I. PMID 9217223.  
  • Ward BK, Stuckey BG, Gutteridge DH, et al. (1997). "A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia.". Hum. Mutat. 10 (3): 233–5. doi:10.1002/(SICI)1098-1004(1997)10:3<233::AID-HUMU9>3.0.CO;2-J. PMID 9298824.  
  • Quinn SJ, Kifor O, Trivedi S, et al. (1998). "Sodium and ionic strength sensing by the calcium receptor.". J. Biol. Chem. 273 (31): 19579–86. doi:10.1074/jbc.273.31.19579. PMID 9677383.  

External links



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