ID CASR_HUMAN Reviewed; 1078 AA. AC P41180; Q13912; Q16108; Q16109; Q16110; Q16379; Q2M1T0; Q4PJ19; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2017, sequence version 3. DT 27-MAR-2024, entry version 228. DE RecName: Full=Extracellular calcium-sensing receptor {ECO:0000305}; DE Short=CaR {ECO:0000303|PubMed:7759551, ECO:0000303|PubMed:8813042}; DE Short=CaSR; DE Short=hCasR {ECO:0000303|PubMed:27386547}; DE AltName: Full=Parathyroid cell calcium-sensing receptor 1 {ECO:0000303|PubMed:8698326}; DE Short=PCaR1 {ECO:0000303|PubMed:8698326}; DE Flags: Precursor; GN Name=CASR {ECO:0000312|HGNC:HGNC:1514}; GN Synonyms=GPRC2A, PCAR1 {ECO:0000303|PubMed:8698326}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HYPOC1 LYS-118; LEU-128; RP MET-151; LYS-191 AND SER-612, AND CHARACTERIZATION OF VARIANTS HYPOC1 RP LEU-128; MET-151 AND LYS-191. RX PubMed=8813042; DOI=10.1056/nejm199610103351505; RA Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., RA Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., RA Thakker R.V.; RT "A familial syndrome of hypocalcemia with hypercalciuria due to mutations RT in the calcium-sensing receptor."; RL N. Engl. J. Med. 335:1115-1122(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND VARIANT RP GLY-990. RC TISSUE=Parathyroid; RX PubMed=7759551; DOI=10.1074/jbc.270.21.12919; RA Garrett J.E., Capuano I.V., Hammerland L.G., Hung B.C., Brown E.M., RA Hebert S.C., Nemeth E.F., Fuller F.; RT "Molecular cloning and functional expression of human parathyroid calcium RT receptor cDNAs."; RL J. Biol. Chem. 270:12919-12925(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=7677761; DOI=10.1006/bbrc.1995.2318; RA Aida K., Koishi S., Tawata M., Onaya T.; RT "Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human RT kidney."; RL Biochem. Biophys. Res. Commun. 214:524-529(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8756555; DOI=10.1210/endo.137.9.8756555; RA Freichel M., Zink-Lorenz A., Holloschi A., Hafner M., Flockerzi V., RA Raue F.; RT "Expression of a calcium-sensing receptor in a human medullary thyroid RT carcinoma cell line and its contribution to calcitonin secretion."; RL Endocrinology 137:3842-3848(1996). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-986; GLY-990 AND RP GLN-1011. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-61, AND VARIANT HHC1 ALA-39. RX PubMed=7673400; DOI=10.1210/jcem.80.9.7673400; RA Aida K., Koishi S., Inoue M., Nakazato M., Tawata M., Onaya T.; RT "Familial hypocalciuric hypercalcemia associated with mutation in the human RT Ca(2+)-sensing receptor gene."; RL J. Clin. Endocrinol. Metab. 80:2594-2598(1995). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 643-908. RX PubMed=8613532; DOI=10.1172/jci118501; RA Bikle D.D., Ratnam A., Mauro T., Harris J., Pillai S.; RT "Changes in calcium responsiveness and handling during keratinocyte RT differentiation. Potential role of the calcium receptor."; RL J. Clin. Invest. 97:1085-1093(1996). RN [9] RP INTERACTION WITH VCP AND RNF19A, GLYCOSYLATION, AND UBIQUITINATION. RX PubMed=16513638; DOI=10.1074/jbc.m513552200; RA Huang Y., Niwa J., Sobue G., Breitwieser G.E.; RT "Calcium-sensing receptor ubiquitination and degradation mediated by the E3 RT ubiquitin ligase dorfin."; RL J. Biol. Chem. 281:11610-11617(2006). RN [10] RP DOMAIN. RX PubMed=17360426; DOI=10.1073/pnas.0611577104; RA Muto T., Tsuchiya D., Morikawa K., Jingami H.; RT "Structures of the extracellular regions of the group II/III metabotropic RT glutamate receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 104:3759-3764(2007). RN [11] RP SUBCELLULAR LOCATION, AND GLYCOSYLATION. RX PubMed=20861236; DOI=10.1210/en.2010-0422; RA Zhuang X., Adipietro K.A., Datta S., Northup J.K., Ray K.; RT "Rab1 small GTP-binding protein regulates cell surface trafficking of the RT human calcium-sensing receptor."; RL Endocrinology 151:5114-5123(2010). RN [12] RP ACTIVITY REGULATION, AND MUTAGENESIS OF CYS-482. RX PubMed=26290606; DOI=10.1124/mol.115.098392; RA Alexander S.T., Hunter T., Walter S., Dong J., Maclean D., Baruch A., RA Subramanian R., Tomlinson J.; RT "Critical cysteine residues in both the calcium-sensing receptor and the RT allosteric activator AMG 416 underlie the mechanism of action."; RL Mol. Pharmacol. 88:853-865(2015). RN [13] {ECO:0007744|PDB:5K5S, ECO:0007744|PDB:5K5T} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 20-607 IN COMPLEX WITH CALCIUM; RP PHOSPHATE AND SULFATE ANIONS AND TRYPTOPHAN, FUNCTION, ACTIVITY REGULATION, RP DOMAIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-261; ASN-287; ASN-446; RP ASN-468; ASN-488; ASN-541 AND ASN-594, MUTAGENESIS OF ARG-69; ASN-102; RP THR-145; SER-147; SER-170; TYR-218; SER-417 AND TRP-458, CHARACTERIZATION RP OF VARIANTS NSHPT ILE-100; LEU-227 AND LYS-551, AND CHARACTERIZATION OF RP VARIANTS HHC1 HIS-66; MET-81; PRO-159; GLY-172; GLY-215; LYS-297 AND RP GLU-557. RX PubMed=27434672; DOI=10.7554/elife.13662; RA Geng Y., Mosyak L., Kurinov I., Zuo H., Sturchler E., Cheng T.C., RA Subramanyam P., Brown A.P., Brennan S.C., Mun H.C., Bush M., Chen Y., RA Nguyen T.X., Cao B., Chang D.D., Quick M., Conigrave A.D., Colecraft H.M., RA McDonald P., Fan Q.R.; RT "Structural mechanism of ligand activation in human calcium-sensing RT receptor."; RL Elife 5:0-0(2016). RN [14] {ECO:0007744|PDB:5FBH, ECO:0007744|PDB:5FBK} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 20-541 IN COMPLEX WITH MAGNESIUM RP AND TRYPTOPHAN, FUNCTION, ACTIVITY REGULATION, DOMAIN, DISULFIDE BONDS, AND RP MUTAGENESIS OF GLU-297. RX PubMed=27386547; DOI=10.1126/sciadv.1600241; RA Zhang C., Zhang T., Zou J., Miller C.L., Gorkhali R., Yang J.Y., RA Schilmiller A., Wang S., Huang K., Brown E.M., Moremen K.W., Hu J., RA Yang J.J.; RT "Structural basis for regulation of human calcium-sensing receptor by RT magnesium ions and an unexpected tryptophan derivative co-agonist."; RL Sci. Adv. 2:E1600241-E1600241(2016). RN [15] RP VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795. RX PubMed=7916660; DOI=10.1016/0092-8674(93)90617-y; RA Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., RA Steinmann B., Levi T., Seidman C.E., Seidman J.G.; RT "Mutations in the human Ca(2+)-sensing receptor gene cause familial RT hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism."; RL Cell 75:1297-1303(1993). RN [16] RP VARIANT HYPOC1 ALA-127. RX PubMed=7874174; DOI=10.1038/ng1194-303; RA Pollak M.R., Brown E.M., Estep H.L., McLaine P.N., Kifor O., Park J., RA Hebert S.C., Seidman C.E., Seidman J.G.; RT "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene RT mutation."; RL Nat. Genet. 8:303-307(1994). RN [17] RP VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227. RX PubMed=7726161; RA Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., RA Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., RA Seidman C.E.; RT "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial RT hypocalciuric hypercalcemia."; RL Am. J. Hum. Genet. 56:1075-1079(1995). RN [18] RP VARIANTS NSHPT LEU-227 AND TYR-582. RX PubMed=8675635; DOI=10.1172/jci118335; RA Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., RA Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V.; RT "Calcium-sensing receptor mutations in familial benign hypercalcemia and RT neonatal hyperparathyroidism."; RL J. Clin. Invest. 96:2683-2692(1995). RN [19] RP VARIANT FIH MET-151. RX PubMed=8698326; DOI=10.1007/s004390050174; RA Lovlie R., Eiken H.G., Sorheim J.I., Boman H.; RT "The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated RT autosomal dominant hypoparathyroidism."; RL Hum. Genet. 98:129-133(1996). RN [20] RP VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, AND VARIANT SER-851. RX PubMed=8733126; DOI=10.1093/hmg/5.5.601; RA Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., RA Zimmerman D., Cutler G.B. Jr.; RT "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and RT sporadic hypoparathyroidism."; RL Hum. Mol. Genet. 5:601-606(1996). RN [21] RP VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143; GLN-185; LYS-297 AND RP TRP-795, VARIANT HYPOC1 ALA-127, FUNCTION, SUBCELLULAR LOCATION, RP GLYCOSYLATION, CHARACTERIZATION OF VARIANTS HHC1 MET-62; CYS-66; MET-138; RP GLU-143; GLN-185; LYS-297 AND TRP-795, AND CHARACTERIZATION OF VARIANT RP HYPOC1 ALA-127. RX PubMed=8702647; DOI=10.1074/jbc.271.32.19537; RA Bai M., Quinn S., Trivedi S., Kifor O., Pearce S.H.S., Pollak M.R., RA Krapcho K., Hebert S.C., Brown E.M.; RT "Expression and characterization of inactivating and activating mutations RT in the human Ca2+o-sensing receptor."; RL J. Biol. Chem. 271:19537-19545(1996). RN [22] RP VARIANTS HHC1 PRO-53; LEU-55; GLN-185; GLY-215; TYR-657 AND ARG-748, RP VARIANTS SER-986; GLY-990 AND GLN-1011, AND CHARACTERIZATION OF VARIANTS RP HHC1 PRO-53; LEU-55 AND GLY-215. RX PubMed=8636323; DOI=10.1210/jcem.81.4.8636323; RA Heath H. III, Odelberg S., Jackson C.E., Teh B.T., Hayward N., Larsson C., RA Buist N.R., Krapcho K.J., Hung B.C., Capuano I.V., Garrett J.E., RA Leppert M.F.; RT "Clustered inactivating mutations and benign polymorphisms of the calcium RT receptor gene in familial benign hypocalciuric hypercalcemia suggest RT receptor functional domains."; RL J. Clin. Endocrinol. Metab. 81:1312-1317(1996). RN [23] RP VARIANTS HHC1 LEU-55; ASP-178; SER-221 AND ILE-817, VARIANTS HYPOC1 RP LEU-128; MET-151 AND LYS-191, VARIANT NSHPT LEU-227, CHARACTERIZATION OF RP VARIANTS HHC1 LEU-55; ASP-178; SER-221 AND ILE-817, FUNCTION, RP CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191, AND RP CHARACTERIZATION OF VARIANT NSHPT LEU-227. RX PubMed=8878438; DOI=10.1172/jci118987; RA Pearce S.H.S., Bai M., Quinn S.J., Kifor O., Brown E.M., Thakker R.V.; RT "Functional characterization of calcium-sensing receptor mutations RT expressed in human embryonic kidney cells."; RL J. Clin. Invest. 98:1860-1866(1996). RN [24] RP VARIANT HHC1 ARG-174. RX PubMed=9298824; RX DOI=10.1002/(sici)1098-1004(1997)10:3<233::aid-humu9>3.0.co;2-j; RA Ward B.K., Stuckey B.G.A., Gutteridge D.H., Laing N.G., Pullan P.T., RA Ratajczak T.; RT "A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with RT familial hypocalciuric hypercalcemia."; RL Hum. Mutat. 10:233-235(1997). RN [25] RP VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, AND CHARACTERIZATION OF RP VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806. RX PubMed=9253358; DOI=10.1210/jcem.82.8.4166; RA De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., RA Spiegel A.M., Baron J.; RT "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations RT of the Ca(2+)-sensing receptor."; RL J. Clin. Endocrinol. Metab. 82:2710-2715(1997). RN [26] RP VARIANT NSHPT GLU-670. RX PubMed=9253359; DOI=10.1210/jcem.82.8.4135; RA Kobayashi M., Tanaka H., Tsuzuki K., Tsuyuki M., Igaki H., Ichinose Y., RA Aya K., Nishioka N., Seino Y.; RT "Two novel missense mutations in calcium-sensing receptor gene associated RT with neonatal severe hyperparathyroidism."; RL J. Clin. Endocrinol. Metab. 82:2716-2719(1997). RN [27] RP VARIANT HYPOC1 CYS-788, AND CHARACTERIZATION OF VARIANT HYPOC1 CYS-788. RX PubMed=9661634; DOI=10.1210/jcem.83.7.4920; RA Watanabe T., Bai M., Lane C.R., Matsumoto S., Minamitani K., Minagawa M., RA Niimi H., Brown E.M., Yasuda T.; RT "Familial hypoparathyroidism: identification of a novel gain of function RT mutation in transmembrane domain 5 of the calcium-sensing receptor."; RL J. Clin. Endocrinol. Metab. 83:2497-2502(1998). RN [28] RP VARIANT ARG-27, CHARACTERIZATION OF VARIANT ARG-27, AND INVOLVEMENT IN RP PRIMARY HYPERPARATHYROIDISM. RX PubMed=10468915; DOI=10.1046/j.1365-2265.1999.00729.x; RA Chikatsu N., Fukumoto S., Suzawa M., Tanaka Y., Takeuchi Y., Takeda S., RA Tamura Y., Matsumoto T., Fujita T.; RT "An adult patient with severe hypercalcaemia and hypocalciuria due to a RT novel homozygous inactivating mutation of calcium-sensing receptor."; RL Clin. Endocrinol. (Oxf.) 50:537-543(1999). RN [29] RP VARIANT HYPOC1 ASN-47, AND CHARACTERIZATION OF VARIANT HYPOC1 ASN-47. RX PubMed=9920108; DOI=10.1210/jcem.84.1.5385; RA Okazaki R., Chikatsu N., Nakatsu M., Takeuchi Y., Ajima M., Miki J., RA Fujita T., Arai M., Totsuka Y., Tanaka K., Fukumoto S.; RT "A novel activating mutation in calcium-sensing receptor gene associated RT with a family of autosomal dominant hypocalcemia."; RL J. Clin. Endocrinol. Metab. 84:363-366(1999). RN [30] RP VARIANT HYPOC1 VAL-616, AND CHARACTERIZATION OF VARIANT HYPOC1 VAL-616. RX PubMed=10487661; DOI=10.1210/jcem.84.9.5977; RA Stock J.L., Brown R.S., Baron J., Coderre J.A., Mancilla E., De Luca F., RA Ray K., Mericq M.V.; RT "Autosomal dominant hypoparathyroidism associated with short stature and RT premature osteoarthritis."; RL J. Clin. Endocrinol. Metab. 84:3036-3040(1999). RN [31] RP VARIANT SER-986, AND ASSOCIATION WITH SERUM LEVEL OF CALCIUM. RX PubMed=10023897; DOI=10.1016/s0140-6736(98)06434-4; RA Cole D.E.C., Peltekova V.D., Rubin L.A., Hawker G.A., Vieth R., Liew C.C., RA Hwang D.M., Evrovski J., Hendy G.N.; RT "A986S polymorphism of the calcium-sensing receptor and circulating calcium RT concentrations."; RL Lancet 353:112-115(1999). RN [32] RP VARIANT HYPERCALCIURIC HYPERCALCEMIA LEU-881, AND CHARACTERIZATION OF RP VARIANT HYPERCALCIURIC HYPERCALCEMIA LEU-881. RX PubMed=10843194; DOI=10.1210/jcem.85.5.6477; RA Carling T., Szabo E., Bai M., Ridefelt P., Westin G., Gustavsson P., RA Trivedi S., Hellman P., Brown E.M., Dahl N., Rastad J.; RT "Familial hypercalcemia and hypercalciuria caused by a novel mutation in RT the cytoplasmic tail of the calcium receptor."; RL J. Clin. Endocrinol. Metab. 85:2042-2047(2000). RN [33] RP VARIANT HHC1 GLU-557. RX PubMed=11762699; DOI=10.1385/endo:15:3:277; RA Nakayama T., Minato M., Nakagawa M., Soma M., Tobe H., Aoi N., Kosuge K., RA Sato M., Ozawa Y., Kanmatsuse K., Kokubun S.; RT "A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric RT hypercalcemia."; RL Endocrine 15:277-282(2001). RN [34] RP VARIANT SER-986, ASSOCIATION WITH SERUM LEVEL OF CALCIUM, AND PREDISPOSING RP FACTOR IN DISORDERS OF BONE AND MINERAL METABOLISM. RX PubMed=11161843; DOI=10.1006/mgme.2000.3126; RA Cole D.E.C., Vieth R., Trang H.M., Wong B.Y.-L., Hendy G.N., Rubin L.A.; RT "Association between total serum calcium and the A986S polymorphism of the RT calcium-sensing receptor gene."; RL Mol. Genet. Metab. 72:168-174(2001). RN [35] RP VARIANT HYPOC1 PHE-820, CHARACTERIZATION OF VARIANT HYPOC1 PHE-820, AND RP VARIANT GLY-990. RX PubMed=12050233; DOI=10.1210/jcem.87.6.8531; RA Nagase T., Murakami T., Tsukada T., Kitamura R., Chikatsu N., Takeo H., RA Takata N., Yasuda H., Fukumoto S., Tanaka Y., Nagata N., Yamaguchi K., RA Akatsu T., Yamamoto M.; RT "A family of autosomal dominant hypocalcemia with a positive correlation RT between serum calcium and magnesium: identification of a novel gain of RT function mutation (Ser(820)Phe) in the calcium-sensing receptor."; RL J. Clin. Endocrinol. Metab. 87:2681-2687(2002). RN [36] RP VARIANTS HYPOC1 PRO-125 AND GLU-843, AND CHARACTERIZATION OF VARIANTS RP HYPOC1 PRO-125 AND GLU-843. RX PubMed=12107202; DOI=10.1210/jcem.87.7.8639; RA Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., RA Shinohara N., Fujieda K.; RT "Hydrochlorothiazide effectively reduces urinary calcium excretion in two RT Japanese patients with gain-of-function mutations of the calcium-sensing RT receptor gene."; RL J. Clin. Endocrinol. Metab. 87:3068-3073(2002). RN [37] RP VARIANTS HYPOC1 TRP-131 AND GLU-843. RX PubMed=12241879; DOI=10.1016/s0140-6736(02)09842-2; RA Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., RA Chikatsu N., Fujita T.; RT "Association between activating mutations of calcium-sensing receptor and RT Bartter's syndrome."; RL Lancet 360:692-694(2002). RN [38] RP VARIANT HYPOC1 LYS-604, AND CHARACTERIZATION OF VARIANT HYPOC1 LYS-604. RX PubMed=12574188; DOI=10.1210/jc.2002-020081; RA Tan Y.M., Cardinal J., Franks A.H., Mun H.-C., Lewis N., Harris L.B., RA Prins J.B., Conigrave A.D.; RT "Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in RT the cysteine-rich domain of the calcium-sensing receptor."; RL J. Clin. Endocrinol. Metab. 88:605-610(2003). RN [39] RP VARIANT HYPOC1 LEU-788, AND CHARACTERIZATION OF VARIANT HYPOC1 LEU-788. RX PubMed=12915654; DOI=10.1210/jc.2003-030409; RA Hendy G.N., Minutti C., Canaff L., Pidasheva S., Yang B., Nouhi Z., RA Zimmerman D., Wei C., Cole D.E.C.; RT "Recurrent familial hypocalcemia due to germline mosaicism for an RT activating mutation of the calcium-sensing receptor gene."; RL J. Clin. Endocrinol. Metab. 88:3674-3681(2003). RN [40] RP VARIANTS SER-986; GLY-990 AND GLN-1011, AND ASSOCIATION WITH SERUM LEVEL OF RP CALCIUM. RX PubMed=15531522; DOI=10.1210/jc.2004-0129; RA Scillitani A., Guarnieri V., De Geronimo S., Muscarella L.A., Battista C., RA D'Agruma L., Bertoldo F., Florio C., Minisola S., Hendy G.N., Cole D.E.C.; RT "Blood ionized calcium is associated with clustered polymorphisms in the RT carboxyl-terminal tail of the calcium-sensing receptor."; RL J. Clin. Endocrinol. Metab. 89:5634-5638(2004). RN [41] RP VARIANT HHC1 PRO-13, AND CHARACTERIZATION OF VARIANT HHC1 PRO-13. RX PubMed=15579740; DOI=10.1210/jc.2004-1046; RA Miyashiro K., Kunii I., Manna T.D., de Menezes Filho H.C., Damiani D., RA Setian N., Hauache O.M.; RT "Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel RT inactivating mutation of the calcium-sensing receptor."; RL J. Clin. Endocrinol. Metab. 89:5936-5941(2004). RN [42] RP VARIANTS NSHPT ILE-100; LYS-336 DEL; PRO-650 AND MET-689, AND VARIANTS RP SER-986; GLY-990 AND GLN-1011. RX PubMed=14985373; DOI=10.1136/jmg.2003.016725; RA Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., RA Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., RA Teh B.T., Prins J.B., Cardinal J.; RT "Genetic testing in familial isolated hyperparathyroidism: unexpected RT results and their implications."; RL J. Med. Genet. 41:155-160(2004). RN [43] RP VARIANT HYPOC1 LYS-767, AND VARIANT GLY-990. RX PubMed=15551332; DOI=10.1002/ajmg.a.30403; RA Uckun-Kitapci A., Underwood L.E., Zhang J., Moats-Staats B.; RT "A novel mutation (E767K) in the second extracellular loop of the calcium RT sensing receptor in a family with autosomal dominant hypocalcemia."; RL Am. J. Med. Genet. A 132:125-129(2005). RN [44] RP VARIANTS HHC1 SER-11 AND PRO-13, VARIANT ALA-14, CHARACTERIZATION OF RP VARIANTS HHC1 SER-11 AND PRO-13, AND CHARACTERIZATION OF VARIANT ALA-14. RX PubMed=15879434; DOI=10.1093/hmg/ddi176; RA Pidasheva S., Canaff L., Simonds W.F., Marx S.J., Hendy G.N.; RT "Impaired cotranslational processing of the calcium-sensing receptor due to RT signal peptide missense mutations in familial hypocalciuric RT hypercalcemia."; RL Hum. Mol. Genet. 14:1679-1690(2005). RN [45] RP VARIANT HHC1 GLN-227, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT RP NSHPT LEU-227, AND CHARACTERIZATION OF VARIANT HHC1 GLN-227. RX PubMed=15572418; DOI=10.1210/jc.2004-1791; RA Wystrychowski A., Pidasheva S., Canaff L., Chudek J., Kokot F., Wiecek A., RA Hendy G.N.; RT "Functional characterization of calcium-sensing receptor codon 227 RT mutations presenting as either familial (benign) hypocalciuric RT hypercalcemia or neonatal hyperparathyroidism."; RL J. Clin. Endocrinol. Metab. 90:864-870(2005). RN [46] RP VARIANT HHC1 GLN-465, CHARACTERIZATION OF VARIANT HHC1 GLN-465, AND VARIANT RP SER-986. RX PubMed=16598859; DOI=10.1016/j.bbrc.2006.02.018; RA Leech C., Lohse P., Stanojevic V., Lechner A., Goeke B., Spitzweg C.; RT "Identification of a novel inactivating R465Q mutation of the calcium- RT sensing receptor."; RL Biochem. Biophys. Res. Commun. 342:996-1002(2006). RN [47] RP VARIANTS HHC1 CYS-66; HIS-66 AND 583-ASN--SER-1078 DEL, SUBCELLULAR RP LOCATION, SUBUNIT, GLYCOSYLATION, AND CHARACTERIZATION OF VARIANTS CYS-66; RP HIS-66 AND 583-ASN--SER-1078 DEL. RX PubMed=16740594; DOI=10.1093/hmg/ddl145; RA Pidasheva S., Grant M., Canaff L., Ercan O., Kumar U., Hendy G.N.; RT "Calcium-sensing receptor dimerizes in the endoplasmic reticulum: RT biochemical and biophysical characterization of CASR mutants retained RT intracellularly."; RL Hum. Mol. Genet. 15:2200-2209(2006). RN [48] RP VARIANT HYPOC1 GLN-727, AND CHARACTERIZATION OF VARIANT HYPOC1 GLN-727. RX PubMed=16608894; DOI=10.1210/jc.2005-2605; RA Mittelman S.D., Hendy G.N., Fefferman R.A., Canaff L., Mosesova I., RA Cole D.E., Burkett L., Geffner M.E.; RT "A hypocalcemic child with a novel activating mutation of the calcium- RT sensing receptor gene: successful treatment with recombinant human RT parathyroid hormone."; RL J. Clin. Endocrinol. Metab. 91:2474-2479(2006). RN [49] RP VARIANT HHC1 CYS-180, AND CHARACTERIZATION OF VARIANT HHC1 CYS-180. RX PubMed=17473068; DOI=10.1210/jc.2007-0123; RA Zajickova K., Vrbikova J., Canaff L., Pawelek P.D., Goltzman D., RA Hendy G.N.; RT "Identification and functional characterization of a novel mutation in the RT calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: RT modulation of clinical severity by vitamin D status."; RL J. Clin. Endocrinol. Metab. 92:2616-2623(2007). RN [50] RP VARIANT NSHPT LYS-551, VARIANT SER-986, FUNCTION, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANT NSHPT LYS-551. RX PubMed=17555508; DOI=10.1111/j.1365-2265.2007.02896.x; RA Toke J., Czirjak G., Patocs A., Enyedi B., Gergics P., Csakvary V., RA Enyedi P., Toth M.; RT "Neonatal severe hyperparathyroidism associated with a novel de novo RT heterozygous R551K inactivating mutation and a heterozygous A986S RT polymorphism of the calcium-sensing receptor gene."; RL Clin. Endocrinol. (Oxf.) 67:385-392(2007). RN [51] RP VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; RP ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; RP ARG-742 AND TRP-886, AND VARIANTS LYS-250; SER-986; GLY-990 AND GLN-1011. RX PubMed=17698911; DOI=10.1210/jc.2007-0322; RA Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L.; RT "Molecular genetic analysis of the calcium sensing receptor gene in RT patients clinically suspected to have familial hypocalciuric hypercalcemia: RT phenotypic variation and mutation spectrum in a Danish population."; RL J. Clin. Endocrinol. Metab. 92:4373-4379(2007). RN [52] RP VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS RP SER-986 AND GLY-990, AND TISSUE SPECIFICITY. RX PubMed=18756473; DOI=10.1002/ana.21428; RA Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., RA Shankar S.K., Anand A.; RT "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense RT mutations in the extracellular calcium sensing receptor gene."; RL Ann. Neurol. 64:158-167(2008). RN [53] RP VARIANT HHC1 ARG-459, VARIANTS SER-986 AND GLN-1011, FUNCTION, AND RP CHARACTERIZATION OF VARIANT HHC1 ARG-459. RX PubMed=19789209; DOI=10.1210/jc.2008-2484; RA Lietman S.A., Tenenbaum-Rakover Y., Jap T.S., Yi-Chi W., De-Ming Y., RA Ding C., Kussiny N., Levine M.A.; RT "A novel loss-of-function mutation, Gln459Arg, of the calcium-sensing RT receptor gene associated with apparent autosomal recessive inheritance of RT familial hypocalciuric hypercalcemia."; RL J. Clin. Endocrinol. Metab. 94:4372-4379(2009). RN [54] RP VARIANTS HHC1 SER-42; LEU-55; HIS-66; MET-81; MET-138; ARG-143; ARG-158; RP GLY-166; TRP-220; ARG-549; TYR-562; GLY-565; TYR-582; 583-ASN--SER-1078 RP DEL; TYR-661; HIS-680; ILE-761 DEL AND TRP-795, AND VARIANTS HYPOC1 RP LYS-118; PHE-125; ARG-129; LYS-228; LYS-604; ILE-802; SER-830; LEU-832 AND RP SER-832. RX PubMed=19179454; DOI=10.1677/jme-08-0164; RA Cole D.E., Yun F.H., Wong B.Y., Shuen A.Y., Booth R.A., Scillitani A., RA Pidasheva S., Zhou X., Canaff L., Hendy G.N.; RT "Calcium-sensing receptor mutations and denaturing high performance liquid RT chromatography."; RL J. Mol. Endocrinol. 42:331-339(2009). RN [55] RP VARIANT THR-339, CHARACTERIZATION OF VARIANT THR-339, AND INVOLVEMENT IN RP PRIMARY HYPERPARATHYROIDISM. RX PubMed=20846291; DOI=10.1111/j.1365-2265.2010.03870.x; RA Hannan F.M., Nesbit M.A., Christie P.T., Lissens W., Van der Schueren B., RA Bex M., Bouillon R., Thakker R.V.; RT "A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is RT associated with isolated primary hyperparathyroidism: correlation between RT location of mutations and severity of hypercalcaemia."; RL Clin. Endocrinol. (Oxf.) 73:715-722(2010). RN [56] RP VARIANT HHC1 ILE-550, FUNCTION, AND CHARACTERIZATION OF VARIANT HHC1 RP ILE-550. RX PubMed=21566075; DOI=10.1530/eje-11-0141; RA Al-Salameh A., Cetani F., Pardi E., Vulpoi C., Pierre P., de Calan L., RA Guyetant S., Jeunemaitre X., Lecomte P.; RT "A novel mutation in the calcium-sensing receptor in a French family with RT familial hypocalciuric hypercalcaemia."; RL Eur. J. Endocrinol. 165:359-363(2011). RN [57] RP VARIANTS HHC1 PRO-159 AND TRP-795, FUNCTION, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANTS HHC1 PRO-159 AND TRP-795. RX PubMed=22114145; DOI=10.1126/scisignal.2002208; RA Grant M.P., Stepanchick A., Cavanaugh A., Breitwieser G.E.; RT "Agonist-driven maturation and plasma membrane insertion of calcium-sensing RT receptors dynamically control signal amplitude."; RL Sci. Signal. 4:RA78-RA78(2011). RN [58] RP VARIANT HHC1 MET-697. RX PubMed=21643651; DOI=10.1007/s00431-011-1504-8; RA Aparicio Lopez C., Anton-Martin P., Gil-Fournier B., Ramiro-Leon S., RA Perez-Nanclares G., Perez de Nanclares G., Martinez Menendez B., RA Castano L.; RT "Familial hypocalciuric hypercalcemia: new mutation in the CASR gene RT converting valine 697 to methionine."; RL Eur. J. Pediatr. 171:147-150(2012). RN [59] RP VARIANTS HHC1 THR-110 AND GLY-172, VARIANTS HYPOC1 CYS-122; HIS-569 AND RP THR-839, FUNCTION, CHARACTERIZATION OF VARIANTS HHC1 THR-110 AND GLY-172, RP AND CHARACTERIZATION OF VARIANTS HYPOC1 CYS-122; HIS-569 AND THR-839. RX PubMed=23966241; DOI=10.1210/jc.2013-1974; RA Nakamura A., Hotsubo T., Kobayashi K., Mochizuki H., Ishizu K., Tajima T.; RT "Loss-of-function and gain-of-function mutations of calcium-sensing RT receptor: functional analysis and the effect of allosteric modulators NPS RT R-568 and NPS 2143."; RL J. Clin. Endocrinol. Metab. 98:E1692-E1701(2013). RN [60] RP VARIANT HHC1 SER-802, AND VARIANT HYPOC1 ILE-802. RX PubMed=23169696; DOI=10.1530/eje-12-0714; RA Lia-Baldini A.S., Magdelaine C., Nizou A., Airault C., Salles J.P., RA Moulin P., Delemer B., Aitouares M., Funalot B., Sturtz F., RA Lienhardt-Roussie A.; RT "Two novel mutations of the calcium-sensing receptor gene affecting the RT same amino acid position lead to opposite phenotypes and reveal the RT importance of p.N802 on receptor activity."; RL Eur. J. Endocrinol. 168:K27-K34(2013). RN [61] RP VARIANT HHC1 MET-972, FUNCTION, AND CHARACTERIZATION OF VARIANT HHC1 RP MET-972. RX PubMed=25292184; DOI=10.1186/1472-6823-14-81; RA Mastromatteo E., Lamacchia O., Campo M.R., Conserva A., Baorda F., RA Cinque L., Guarnieri V., Scillitani A., Cignarelli M.; RT "A novel mutation in calcium-sensing receptor gene associated to RT hypercalcemia and hypercalciuria."; RL BMC Endocr. Disord. 14:81-81(2014). RN [62] RP VARIANTS HHC1 VAL-707 AND SER-774, FUNCTION, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANTS HHC1 VAL-707 AND SER-774. RX PubMed=25104082; DOI=10.1093/ndt/gfu065; RA Stratta P., Merlotti G., Musetti C., Quaglia M., Pagani A., Izzo C., RA Radin E., Airoldi A., Baorda F., Palladino T., Leone M.P., Guarnieri V.; RT "Calcium-sensing-related gene mutations in hypercalcaemic hypocalciuric RT patients as differential diagnosis from primary hyperparathyroidism: RT detection of two novel inactivating mutations in an Italian population."; RL Nephrol. Dial. Transplant. 29:1902-1909(2014). RN [63] RP VARIANT HHC1 TRP-571, FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION RP OF VARIANT HHC1 TRP-571. RX PubMed=26386835; DOI=10.1007/s00774-015-0713-z; RA Kim E.S., Kim S.Y., Lee J.Y., Han J.H., Sohn T.S., Son H.S., Moon S.D.; RT "Identification and functional analysis of a novel CaSR mutation in a RT family with familial hypocalciuric hypercalcemia."; RL J. Bone Miner. Metab. 34:662-667(2016). RN [64] RP VARIANT HYPOC1 LEU-136, FUNCTION, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANT HYPOC1 LEU-136. RX PubMed=25766501; DOI=10.1016/j.mce.2015.02.021; RA Baran N., ter Braak M., Saffrich R., Woelfle J., Schmitz U.; RT "Novel activating mutation of human calcium-sensing receptor in a family RT with autosomal dominant hypocalcaemia."; RL Mol. Cell. Endocrinol. 407:18-25(2015). RN [65] RP VARIANTS HYPOC1 LEU-221; ARG-681 AND GLN-727, FUNCTION, SUBCELLULAR RP LOCATION, AND CHARACTERIZATION OF VARIANTS HYPOC1 ARG-681 AND GLN-727. RX PubMed=22789683; DOI=10.1016/j.ymgme.2012.06.012; RA Guarnieri V., Valentina D'Elia A., Baorda F., Pazienza V., Benegiamo G., RA Stanziale P., Copetti M., Battista C., Grimaldi F., Damante G., RA Pellegrini F., D'Agruma L., Zelante L., Carella M., Scillitani A.; RT "CASR gene activating mutations in two families with autosomal dominant RT hypocalcemia."; RL Mol. Genet. Metab. 107:548-552(2012). CC -!- FUNCTION: G-protein-coupled receptor that senses changes in the CC extracellular concentration of calcium ions and plays a key role in CC maintaining calcium homeostasis (PubMed:7759551, PubMed:8702647, CC PubMed:8636323, PubMed:8878438, PubMed:17555508, PubMed:19789209, CC PubMed:21566075, PubMed:22114145, PubMed:23966241, PubMed:25292184, CC PubMed:25104082, PubMed:26386835, PubMed:25766501, PubMed:22789683). CC Senses fluctuations in the circulating calcium concentration and CC modulates the production of parathyroid hormone (PTH) in parathyroid CC glands (By similarity). The activity of this receptor is mediated by a CC G-protein that activates a phosphatidylinositol-calcium second CC messenger system (PubMed:7759551). The G-protein-coupled receptor CC activity is activated by a co-agonist mechanism: aromatic amino acids, CC such as Trp or Phe, act concertedly with divalent cations, such as CC calcium or magnesium, to achieve full receptor activation CC (PubMed:27434672, PubMed:27386547). {ECO:0000250|UniProtKB:Q9QY96, CC ECO:0000269|PubMed:17555508, ECO:0000269|PubMed:19789209, CC ECO:0000269|PubMed:21566075, ECO:0000269|PubMed:22114145, CC ECO:0000269|PubMed:22789683, ECO:0000269|PubMed:23966241, CC ECO:0000269|PubMed:25104082, ECO:0000269|PubMed:25292184, CC ECO:0000269|PubMed:25766501, ECO:0000269|PubMed:26386835, CC ECO:0000269|PubMed:27386547, ECO:0000269|PubMed:27434672, CC ECO:0000269|PubMed:7759551, ECO:0000269|PubMed:8636323, CC ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8878438}. CC -!- ACTIVITY REGULATION: In resting state, adopts an open conformation, CC anion-binding promoting the inactive configuration (PubMed:27434672). CC Upon aromatic amino acid-binding, the groove in the extracellular venus CC flytrap module is closed, thereby inducing the formation of a novel CC homodimer interface between subunits (PubMed:27434672, CC PubMed:27386547). Calcium ions stabilize the active state by enhancing CC homodimer interactions between membrane-proximal domains to fully CC activate the receptor (PubMed:27434672, PubMed:27386547). Activated by CC AMG 416, a D-amino acid-containing peptide agonist that is being CC evaluated for the treatment of secondary hyperparathyroidism in chronic CC kidney disease patients receiving hemodialysis (PubMed:26290606). AMG CC 416 agonist acts by forming a disulfide bond with Cys-482 CC (PubMed:26290606). {ECO:0000269|PubMed:26290606, CC ECO:0000269|PubMed:27386547, ECO:0000269|PubMed:27434672}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:27434672, PubMed:27386547, CC PubMed:16740594). Interacts with VCP and RNF19A (PubMed:16513638). CC Interacts with ARRB1 (By similarity). {ECO:0000250|UniProtKB:P48442, CC ECO:0000269|PubMed:16513638, ECO:0000269|PubMed:16740594, CC ECO:0000269|PubMed:27386547, ECO:0000269|PubMed:27434672}. CC -!- INTERACTION: CC P41180; Q15363: TMED2; NbExp=3; IntAct=EBI-4400127, EBI-998485; CC P41180-1; P41180-1: CASR; NbExp=2; IntAct=EBI-27048496, EBI-27048496; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15572418, CC ECO:0000269|PubMed:16740594, ECO:0000269|PubMed:17555508, CC ECO:0000269|PubMed:19789209, ECO:0000269|PubMed:20861236, CC ECO:0000269|PubMed:22114145, ECO:0000269|PubMed:22789683, CC ECO:0000269|PubMed:25104082, ECO:0000269|PubMed:25766501, CC ECO:0000269|PubMed:26386835, ECO:0000269|PubMed:8702647}; Multi-pass CC membrane protein {ECO:0000269|PubMed:20861236}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P41180-1; Sequence=Displayed; CC Name=2; CC IsoId=P41180-2; Sequence=VSP_002035; CC -!- TISSUE SPECIFICITY: Expressed in the temporal lobe, frontal lobe, CC parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, CC liver, heart, skeletal muscle, placenta. {ECO:0000269|PubMed:18756473}. CC -!- DOMAIN: The extracellular regions of the homodimer interact in a side- CC by-side fashion while facing opposite directions (PubMed:27434672, CC PubMed:27386547). Each extracellular region consists of three domains, CC LB1 (ligand-binding 1), LB2 and CR (cysteine-rich) (PubMed:17360426). CC The two lobe-shaped domains LB1 and LB2 form a venus flytrap module CC (PubMed:27434672, PubMed:27386547). In the inactive configuration, the CC venus flytrap modules of both protomers are in the open conformation CC associated with the resting state (open-open) and the interdomain cleft CC is empty (PubMed:27434672). In addition, each protomer contains three CC anions, which reinforce the inactive conformation, and one calcium ion CC (PubMed:27434672). In the active configuration, both protomers of CC extracellular regions have the closed conformation associated with CC agonist-binding (closed-closed) (PubMed:27434672, PubMed:27386547). The CC ligand-binding cleft of each protomer is solely occupied by an aromatic CC amino-acid (PubMed:27434672, PubMed:27386547). Calcium is bound at four CC novel sites, including one at the homodimer interface (PubMed:27434672, CC PubMed:27386547). Agonist-binding induces large conformational changes CC within the extracellular region homodimer: first, the venus flytrap CC module of each protomer undergoes domain closure (PubMed:27434672, CC PubMed:27386547). Second, the LB2 regions of the two protomers approach CC each other, resulting in an expansion of the homodimer interactions CC involving LB2 domains (PubMed:27434672, PubMed:27386547). Third, the CR CC regions of the two subunits interact to form a large homodimer CC interface that is unique to the active state (PubMed:27434672, CC PubMed:27386547). The CR regions are brought into close contact by the CC motion involving LB2 since the two domains are rigidly associated CC within each subunit (PubMed:27434672, PubMed:27386547). CC {ECO:0000269|PubMed:27386547, ECO:0000269|PubMed:27434672, CC ECO:0000303|PubMed:17360426}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16513638, CC ECO:0000269|PubMed:16740594, ECO:0000269|PubMed:20861236, CC ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:8702647}. CC -!- PTM: Ubiquitinated by RNF19A; which induces proteasomal degradation. CC {ECO:0000269|PubMed:16513638}. CC -!- DISEASE: Hypocalciuric hypercalcemia, familial 1 (HHC1) [MIM:145980]: A CC form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis CC that is transmitted as an autosomal dominant trait with a high degree CC of penetrance. It is characterized biochemically by lifelong elevation CC of serum calcium concentrations and is associated with inappropriately CC low urinary calcium excretion and a normal or mildly elevated CC circulating parathyroid hormone level. Hypermagnesemia is typically CC present. Affected individuals are usually asymptomatic and the disorder CC is considered benign. However, chondrocalcinosis and pancreatitis occur CC in some adults. {ECO:0000269|PubMed:11762699, CC ECO:0000269|PubMed:15572418, ECO:0000269|PubMed:15579740, CC ECO:0000269|PubMed:15879434, ECO:0000269|PubMed:16598859, CC ECO:0000269|PubMed:16740594, ECO:0000269|PubMed:17473068, CC ECO:0000269|PubMed:17698911, ECO:0000269|PubMed:19179454, CC ECO:0000269|PubMed:19789209, ECO:0000269|PubMed:21566075, CC ECO:0000269|PubMed:21643651, ECO:0000269|PubMed:22114145, CC ECO:0000269|PubMed:23169696, ECO:0000269|PubMed:23966241, CC ECO:0000269|PubMed:25104082, ECO:0000269|PubMed:25292184, CC ECO:0000269|PubMed:26386835, ECO:0000269|PubMed:27434672, CC ECO:0000269|PubMed:7673400, ECO:0000269|PubMed:7726161, CC ECO:0000269|PubMed:7916660, ECO:0000269|PubMed:8636323, CC ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8878438, CC ECO:0000269|PubMed:9298824}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hyperparathyroidism, neonatal severe (NSHPT) [MIM:239200]: A CC disorder characterized by severe hypercalcemia, bone demineralization, CC and failure to thrive usually manifesting in the first 6 months of CC life. If untreated, NSHPT can be a devastating neurodevelopmental CC disorder, which in some cases is lethal without parathyroidectomy. CC {ECO:0000269|PubMed:14985373, ECO:0000269|PubMed:15572418, CC ECO:0000269|PubMed:17555508, ECO:0000269|PubMed:27434672, CC ECO:0000269|PubMed:8675635, ECO:0000269|PubMed:8878438, CC ECO:0000269|PubMed:9253359}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hypocalcemia, autosomal dominant 1 (HYPOC1) [MIM:601198]: A CC disorder of mineral homeostasis characterized by blood calcium levels CC below normal, and low or normal serum parathyroid hormone CC concentrations. Disease manifestations include mild or asymptomatic CC hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria CC with nephrocalcinosis or kidney stones, and ectopic and basal ganglia CC calcifications. Few patients manifest hypocalcemia and features of CC Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic CC alkalosis, hyperreninemia, and hyperaldosteronemia. CC {ECO:0000269|PubMed:10487661, ECO:0000269|PubMed:12050233, CC ECO:0000269|PubMed:12107202, ECO:0000269|PubMed:12241879, CC ECO:0000269|PubMed:12574188, ECO:0000269|PubMed:12915654, CC ECO:0000269|PubMed:15551332, ECO:0000269|PubMed:16608894, CC ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:22789683, CC ECO:0000269|PubMed:23169696, ECO:0000269|PubMed:23966241, CC ECO:0000269|PubMed:25766501, ECO:0000269|PubMed:7874174, CC ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8733126, CC ECO:0000269|PubMed:8813042, ECO:0000269|PubMed:8878438, CC ECO:0000269|PubMed:9253358, ECO:0000269|PubMed:9661634, CC ECO:0000269|PubMed:9920108}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Epilepsy, idiopathic generalized 8 (EIG8) [MIM:612899]: A CC disorder characterized by recurring generalized seizures in the absence CC of detectable brain lesions and/or metabolic abnormalities. Seizure CC types are variable, but include myoclonic seizures, absence seizures, CC febrile seizures, complex partial seizures, and generalized tonic- CC clonic seizures. {ECO:0000269|PubMed:18756473}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB29413.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/casr/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X81086; CAA56990.1; -; Genomic_DNA. DR EMBL; U20759; AAA86503.1; -; mRNA. DR EMBL; U20760; AAA86504.1; -; mRNA. DR EMBL; D50855; BAA09453.1; -; mRNA. DR EMBL; S83176; AAB46873.1; -; mRNA. DR EMBL; S79217; AAB35262.2; -; mRNA. DR EMBL; S81755; AAD14370.1; -; mRNA. DR EMBL; S68032; AAB29413.2; ALT_SEQ; Genomic_DNA. DR EMBL; S68033; AAB29414.1; -; Genomic_DNA. DR EMBL; S68036; AAB29415.1; -; Genomic_DNA. DR EMBL; DQ088967; AAY68221.1; -; Genomic_DNA. DR EMBL; BC104999; AAI05000.1; -; mRNA. DR EMBL; BC112236; AAI12237.1; -; mRNA. DR CCDS; CCDS3010.1; -. [P41180-1] DR CCDS; CCDS54632.1; -. [P41180-2] DR PIR; A56715; A56715. DR PIR; B56715; B56715. DR RefSeq; NP_000379.2; NM_000388.3. [P41180-1] DR RefSeq; NP_001171536.1; NM_001178065.1. [P41180-2] DR RefSeq; XP_006713852.1; XM_006713789.3. [P41180-1] DR RefSeq; XP_016862813.1; XM_017007324.1. [P41180-1] DR RefSeq; XP_016862814.1; XM_017007325.1. [P41180-1] DR PDB; 5FBH; X-ray; 2.70 A; A/B=20-541. DR PDB; 5FBK; X-ray; 2.10 A; A/B=20-541. DR PDB; 5K5S; X-ray; 2.60 A; A/B=20-607. DR PDB; 5K5T; X-ray; 3.10 A; A=20-607. DR PDB; 7DTT; EM; 3.80 A; A/B=20-1078. DR PDB; 7DTU; EM; 4.40 A; A/B=20-1078. DR PDB; 7DTV; EM; 3.50 A; A/B=20-1078. DR PDB; 7DTW; EM; 4.50 A; A/B=20-1078. DR PDB; 7E6T; EM; 3.00 A; A/B=20-870. DR PDB; 7E6U; EM; 6.00 A; A/C=20-870. DR PDB; 7M3E; EM; 3.20 A; A/B=20-894. DR PDB; 7M3F; EM; 2.80 A; A/B=20-894. DR PDB; 7M3G; EM; 2.50 A; A/B=20-894. DR PDB; 7M3J; EM; 4.10 A; A/B=20-894. DR PDB; 7SIL; EM; 2.70 A; A/B=1-870. DR PDB; 7SIM; EM; 2.70 A; A/B=1-870. DR PDB; 7SIN; EM; 5.90 A; A/B=1-870. DR PDB; 8WPG; EM; 2.70 A; A/B=20-892. DR PDB; 8WPU; EM; 3.10 A; A/B=20-907. DR PDBsum; 5FBH; -. DR PDBsum; 5FBK; -. DR PDBsum; 5K5S; -. DR PDBsum; 5K5T; -. DR PDBsum; 7DTT; -. DR PDBsum; 7DTU; -. DR PDBsum; 7DTV; -. DR PDBsum; 7DTW; -. DR PDBsum; 7E6T; -. DR PDBsum; 7E6U; -. DR PDBsum; 7M3E; -. DR PDBsum; 7M3F; -. DR PDBsum; 7M3G; -. DR PDBsum; 7M3J; -. DR PDBsum; 7SIL; -. DR PDBsum; 7SIM; -. DR PDBsum; 7SIN; -. DR PDBsum; 8WPG; -. DR PDBsum; 8WPU; -. DR AlphaFoldDB; P41180; -. DR EMDB; EMD-23652; -. DR EMDB; EMD-23653; -. DR EMDB; EMD-23654; -. DR EMDB; EMD-23655; -. DR EMDB; EMD-25143; -. DR EMDB; EMD-25144; -. DR EMDB; EMD-25145; -. DR EMDB; EMD-30853; -. DR EMDB; EMD-30854; -. DR EMDB; EMD-30855; -. DR EMDB; EMD-30856; -. DR EMDB; EMD-30996; -. DR EMDB; EMD-30997; -. DR EMDB; EMD-37716; -. DR EMDB; EMD-37724; -. DR SMR; P41180; -. DR BioGRID; 107296; 22. DR DIP; DIP-5975N; -. DR ELM; P41180; -. DR IntAct; P41180; 1. DR STRING; 9606.ENSP00000420194; -. DR BindingDB; P41180; -. DR ChEMBL; CHEMBL1878; -. DR DrugBank; DB11093; Calcium citrate. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR DrugBank; DB01012; Cinacalcet. DR DrugBank; DB12865; Etelcalcetide. DR DrugBank; DB00994; Neomycin. DR DrugBank; DB05695; NPS-2143. DR DrugBank; DB05255; Ronacaleret. DR DrugBank; DB00127; Spermine. DR DrugCentral; P41180; -. DR GuidetoPHARMACOLOGY; 54; -. DR TCDB; 9.A.14.7.2; the g-protein-coupled receptor (gpcr) family. DR GlyConnect; 1227; 2 N-Linked glycans (1 site). DR GlyCosmos; P41180; 11 sites, 2 glycans. DR GlyGen; P41180; 11 sites, 2 N-linked glycans (1 site). DR iPTMnet; P41180; -. DR PhosphoSitePlus; P41180; -. DR BioMuta; CASR; -. DR DMDM; 1168781; -. DR MassIVE; P41180; -. DR PaxDb; 9606-ENSP00000420194; -. DR PeptideAtlas; P41180; -. DR ProteomicsDB; 55410; -. [P41180-1] DR ProteomicsDB; 55411; -. [P41180-2] DR Antibodypedia; 16753; 751 antibodies from 43 providers. DR DNASU; 846; -. DR Ensembl; ENST00000498619.4; ENSP00000420194.1; ENSG00000036828.17. [P41180-2] DR Ensembl; ENST00000638421.1; ENSP00000492190.1; ENSG00000036828.17. [P41180-1] DR Ensembl; ENST00000639785.2; ENSP00000491584.2; ENSG00000036828.17. [P41180-1] DR GeneID; 846; -. DR KEGG; hsa:846; -. DR MANE-Select; ENST00000639785.2; ENSP00000491584.2; NM_000388.4; NP_000379.3. DR UCSC; uc003eev.5; human. [P41180-1] DR AGR; HGNC:1514; -. DR CTD; 846; -. DR DisGeNET; 846; -. DR GeneCards; CASR; -. DR GeneReviews; CASR; -. DR HGNC; HGNC:1514; CASR. DR HPA; ENSG00000036828; Tissue enriched (parathyroid). DR MalaCards; CASR; -. DR MIM; 145980; phenotype. DR MIM; 239200; phenotype. DR MIM; 601198; phenotype. DR MIM; 601199; gene. DR MIM; 612899; phenotype. DR neXtProt; NX_P41180; -. DR OpenTargets; ENSG00000036828; -. DR Orphanet; 428; Autosomal dominant hypocalcemia. DR Orphanet; 93372; Familial hypocalciuric hypercalcemia type 1. DR Orphanet; 676; Hereditary chronic pancreatitis. DR Orphanet; 417; Neonatal severe primary hyperparathyroidism. DR PharmGKB; PA26097; -. DR VEuPathDB; HostDB:ENSG00000036828; -. DR eggNOG; KOG1056; Eukaryota. DR GeneTree; ENSGT00940000157596; -. DR HOGENOM; CLU_005389_0_0_1; -. DR InParanoid; P41180; -. DR OMA; KCPDDSW; -. DR OrthoDB; 5308018at2759; -. DR PhylomeDB; P41180; -. DR PathwayCommons; P41180; -. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors). DR SignaLink; P41180; -. DR SIGNOR; P41180; -. DR BioGRID-ORCS; 846; 28 hits in 1156 CRISPR screens. DR ChiTaRS; CASR; human. DR GeneWiki; Calcium-sensing_receptor; -. DR GenomeRNAi; 846; -. DR Pharos; P41180; Tclin. DR PRO; PR:P41180; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P41180; Protein. DR Bgee; ENSG00000036828; Expressed in islet of Langerhans and 52 other cell types or tissues. DR ExpressionAtlas; P41180; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0043679; C:axon terminus; IEA:Ensembl. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0016597; F:amino acid binding; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005178; F:integrin binding; IEA:Ensembl. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; TAS:ProtInc. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0032782; P:bile acid secretion; IEA:Ensembl. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl. DR GO; GO:0070509; P:calcium ion import; IDA:UniProtKB. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEA:Ensembl. DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl. DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl. DR GO; GO:0007635; P:chemosensory behavior; TAS:ProtInc. DR GO; GO:1902476; P:chloride transmembrane transport; IEA:Ensembl. DR GO; GO:0005513; P:detection of calcium ion; IDA:UniProtKB. DR GO; GO:0060613; P:fat pad development; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:UniProtKB. DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl. DR GO; GO:0001503; P:ossification; TAS:ProtInc. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0090280; P:positive regulation of calcium ion import; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IEA:Ensembl. DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl. DR GO; GO:0051924; P:regulation of calcium ion transport; IBA:GO_Central. DR GO; GO:0071774; P:response to fibroblast growth factor; IEA:Ensembl. DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl. DR GO; GO:0042311; P:vasodilation; IEA:Ensembl. DR CDD; cd15282; 7tmC_CaSR; 1. DR CDD; cd06364; PBP1_CaSR; 1. DR Gene3D; 3.40.50.2300; -; 2. DR Gene3D; 2.10.50.30; GPCR, family 3, nine cysteines domain; 1. DR InterPro; IPR001828; ANF_lig-bd_rcpt. DR InterPro; IPR000337; GPCR_3. DR InterPro; IPR011500; GPCR_3_9-Cys_dom. DR InterPro; IPR038550; GPCR_3_9-Cys_sf. DR InterPro; IPR017978; GPCR_3_C. DR InterPro; IPR000068; GPCR_3_Ca_sens_rcpt-rel. DR InterPro; IPR017979; GPCR_3_CS. DR InterPro; IPR028082; Peripla_BP_I. DR PANTHER; PTHR24061; CALCIUM-SENSING RECEPTOR-RELATED; 1. DR PANTHER; PTHR24061:SF358; EXTRACELLULAR CALCIUM-SENSING RECEPTOR; 1. DR Pfam; PF00003; 7tm_3; 1. DR Pfam; PF01094; ANF_receptor; 1. DR Pfam; PF07562; NCD3G; 1. DR PRINTS; PR00592; CASENSINGR. DR PRINTS; PR00248; GPCRMGR. DR SUPFAM; SSF53822; Periplasmic binding protein-like I; 1. DR PROSITE; PS00979; G_PROTEIN_RECEP_F3_1; 1. DR PROSITE; PS00980; G_PROTEIN_RECEP_F3_2; 1. DR PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1. DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1. DR Genevisible; P41180; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell membrane; KW Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor; KW Glycoprotein; Membrane; Metal-binding; Phosphoprotein; Receptor; KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..1078 FT /note="Extracellular calcium-sensing receptor" FT /id="PRO_0000012946" FT TOPO_DOM 20..612 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 613..635 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 636..649 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 650..670 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 671..681 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 682..700 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 701..724 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 725..745 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 746..769 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 770..792 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 793..805 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 806..828 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 829..836 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 837..862 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 863..1078 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 22..188 FT /note="Ligand-binding 1 (LB1)" FT /evidence="ECO:0000303|PubMed:17360426" FT REGION 189..324 FT /note="Ligand-binding 2 (LB2)" FT /evidence="ECO:0000303|PubMed:17360426" FT REGION 542..612 FT /note="Cysteine-rich (CR)" FT /evidence="ECO:0000303|PubMed:17360426" FT REGION 880..900 FT /note="Interaction with RNF19A" FT /evidence="ECO:0000269|PubMed:16513638" FT REGION 892..963 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 986..1006 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1030..1055 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 894..963 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 66..70 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /ligand_note="required for structural stability of the FT receptor" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S" FT BINDING 81 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000305|PubMed:27386547, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 84 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000305|PubMed:27386547, ECO:0007744|PDB:5FBK, FT ECO:0007744|PDB:5K5S" FT BINDING 87 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000305|PubMed:27386547, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 88 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000305|PubMed:27386547, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 100 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S, ECO:0007744|PDB:5K5T" FT BINDING 145 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S" FT BINDING 147 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 168 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 170 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 231 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S" FT BINDING 234 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S" FT BINDING 297 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT BINDING 415..417 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /ligand_note="required for structural stability of the FT receptor" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S" FT BINDING 557 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0007744|PDB:5K5S" FT SITE 482 FT /note="Important for ability of agonist AMG 416 to activate FT G-protein-coupled receptor activity" FT /evidence="ECO:0000269|PubMed:26290606" FT MOD_RES 920 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QY96" FT MOD_RES 1061 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QY96" FT CARBOHYD 90 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 130 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 261 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT CARBOHYD 287 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT CARBOHYD 386 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 400 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 446 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT CARBOHYD 468 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT CARBOHYD 488 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT CARBOHYD 541 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT CARBOHYD 594 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:27434672" FT DISULFID 60..101 FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT DISULFID 129 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000305|PubMed:27386547" FT DISULFID 131 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000305|PubMed:27386547" FT DISULFID 236..561 FT /evidence="ECO:0000269|PubMed:27434672" FT DISULFID 358..395 FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT DISULFID 437..449 FT /evidence="ECO:0000269|PubMed:27386547, FT ECO:0000269|PubMed:27434672, ECO:0007744|PDB:5FBH, FT ECO:0007744|PDB:5FBK, ECO:0007744|PDB:5K5S" FT DISULFID 542..562 FT /evidence="ECO:0000269|PubMed:27434672" FT DISULFID 546..565 FT /evidence="ECO:0000269|PubMed:27434672" FT DISULFID 568..582 FT /evidence="ECO:0000269|PubMed:27434672" FT DISULFID 585..598 FT /evidence="ECO:0000269|PubMed:27434672" FT VAR_SEQ 536 FT /note="E -> EPLTFVLSVLQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7759551" FT /id="VSP_002035" FT VARIANT 11 FT /note="L -> S (in HHC1; demonstrates reduced intracellular FT and plasma membrane expression and signaling to the MAPK FT pathway in response to extracellular calcium relative to FT wild-type; fails to be inserted in the microsomes and does FT not undergo proper glycosylation; dbSNP:rs200673016)" FT /evidence="ECO:0000269|PubMed:15879434" FT /id="VAR_058046" FT VARIANT 13 FT /note="L -> P (in HHC1; has a dose-response curve shifted FT to the right relative to that of wild-type; demonstrates FT reduced intracellular and plasma membrane expression and FT signaling to the MAPK pathway in response to extracellular FT calcium relative to wild-type; fails to be inserted in the FT microsomes and does not undergo proper glycosylation; FT dbSNP:rs104893717)" FT /evidence="ECO:0000269|PubMed:15579740, FT ECO:0000269|PubMed:15879434" FT /id="VAR_058047" FT VARIANT 14 FT /note="T -> A (does not demonstrate reduced intracellular FT and plasma membrane expression and signaling to the MAPK FT pathway in response to extracellular calcium relative to FT wild-type; does not fail to be inserted in the microsomes FT and does undergo proper glycosylation; dbSNP:rs199515839)" FT /evidence="ECO:0000269|PubMed:15879434" FT /id="VAR_058048" FT VARIANT 21 FT /note="G -> R (in HHC1; dbSNP:rs1064794290)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058049" FT VARIANT 27 FT /note="Q -> R (found in a patient with primary FT hyperparathyroidism detected at adulthood; mutant CASR is FT activated by a higher calcium concentrations than the FT wild-type)" FT /evidence="ECO:0000269|PubMed:10468915" FT /id="VAR_065198" FT VARIANT 39 FT /note="P -> A (in HHC1; dbSNP:rs121909262)" FT /evidence="ECO:0000269|PubMed:7673400" FT /id="VAR_003585" FT VARIANT 42 FT /note="F -> S (in HHC1; dbSNP:rs1553765909)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078139" FT VARIANT 47 FT /note="K -> N (in HYPOC1; the EC(50) of the mutant is FT significantly lower than that of wild-type; FT dbSNP:rs104893702)" FT /evidence="ECO:0000269|PubMed:9920108" FT /id="VAR_058050" FT VARIANT 53 FT /note="S -> P (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:8636323" FT /id="VAR_078140" FT VARIANT 55 FT /note="P -> L (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs886041154)" FT /evidence="ECO:0000269|PubMed:19179454, FT ECO:0000269|PubMed:8636323, ECO:0000269|PubMed:8878438" FT /id="VAR_078141" FT VARIANT 62 FT /note="R -> M (in HHC1; mild; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs121909265)" FT /evidence="ECO:0000269|PubMed:7726161, FT ECO:0000269|PubMed:8702647" FT /id="VAR_003586" FT VARIANT 66 FT /note="R -> C (in HHC1; does not affect homodimerization; FT impaired N-glycosylation; impaired cell membrane FT localization; decreased G-protein coupled receptor FT signaling pathway; dbSNP:rs121909266)" FT /evidence="ECO:0000269|PubMed:16740594, FT ECO:0000269|PubMed:7726161, ECO:0000269|PubMed:8702647" FT /id="VAR_003587" FT VARIANT 66 FT /note="R -> H (in HHC1; does not affect homodimerization; FT impaired N-glycosylation; impaired cell membrane FT localization; decreased G-protein coupled receptor FT signaling pathway; dbSNP:rs1276839362)" FT /evidence="ECO:0000269|PubMed:16740594, FT ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:27434672" FT /id="VAR_078142" FT VARIANT 81 FT /note="I -> M (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:19179454, FT ECO:0000269|PubMed:27434672" FT /id="VAR_078143" FT VARIANT 100 FT /note="T -> I (in NSHPT; Abolished G-protein coupled FT receptor activity)" FT /evidence="ECO:0000269|PubMed:14985373, FT ECO:0000269|PubMed:27434672" FT /id="VAR_065199" FT VARIANT 110 FT /note="A -> T (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:23966241" FT /id="VAR_078144" FT VARIANT 116 FT /note="A -> T (in HYPOC1; dbSNP:rs104893691)" FT /evidence="ECO:0000269|PubMed:8733126" FT /id="VAR_003588" FT VARIANT 118 FT /note="N -> K (in HYPOC1; the mutation shifts the FT concentration-response curve to the left and increases FT maximal activity; dbSNP:rs104893695)" FT /evidence="ECO:0000269|PubMed:19179454, FT ECO:0000269|PubMed:8813042, ECO:0000269|PubMed:9253358" FT /id="VAR_058051" FT VARIANT 122 FT /note="S -> C (in HYPOC1; increased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:23966241" FT /id="VAR_078145" FT VARIANT 125 FT /note="L -> F (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078146" FT VARIANT 125 FT /note="L -> P (in HYPOC1; shifts the concentration-response FT curve of calcium ions to the left; dbSNP:rs104893708)" FT /evidence="ECO:0000269|PubMed:12107202" FT /id="VAR_058052" FT VARIANT 127 FT /note="E -> A (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; dbSNP:rs121909260)" FT /evidence="ECO:0000269|PubMed:7874174, FT ECO:0000269|PubMed:8702647" FT /id="VAR_003589" FT VARIANT 128 FT /note="F -> L (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; dbSNP:rs104893696)" FT /evidence="ECO:0000269|PubMed:8813042, FT ECO:0000269|PubMed:8878438" FT /id="VAR_058053" FT VARIANT 129 FT /note="C -> R (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078147" FT VARIANT 131 FT /note="C -> W (in HYPOC1; patients with clinical features FT of Bartter syndrome; dbSNP:rs121909267)" FT /evidence="ECO:0000269|PubMed:12241879" FT /id="VAR_058054" FT VARIANT 136 FT /note="P -> L (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:25766501" FT /id="VAR_078148" FT VARIANT 138 FT /note="T -> M (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs121909263)" FT /evidence="ECO:0000269|PubMed:19179454, FT ECO:0000269|PubMed:7726161, ECO:0000269|PubMed:8702647" FT /id="VAR_003590" FT VARIANT 143 FT /note="G -> E (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs121909264)" FT /evidence="ECO:0000269|PubMed:7726161, FT ECO:0000269|PubMed:8702647" FT /id="VAR_003591" FT VARIANT 143 FT /note="G -> R (in HHC1; dbSNP:rs769256610)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078149" FT VARIANT 151 FT /note="T -> M (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; dbSNP:rs104893694)" FT /evidence="ECO:0000269|PubMed:8698326, FT ECO:0000269|PubMed:8813042, ECO:0000269|PubMed:8878438" FT /id="VAR_058055" FT VARIANT 158 FT /note="G -> R (in HHC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078150" FT VARIANT 159 FT /note="L -> P (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:22114145, FT ECO:0000269|PubMed:27434672" FT /id="VAR_078151" FT VARIANT 166 FT /note="S -> G (in HHC1; dbSNP:rs193922441)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078152" FT VARIANT 171 FT /note="S -> N (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058056" FT VARIANT 172 FT /note="R -> G (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs201851934)" FT /evidence="ECO:0000269|PubMed:23966241, FT ECO:0000269|PubMed:27434672" FT /id="VAR_078153" FT VARIANT 174 FT /note="L -> R (in HHC1)" FT /evidence="ECO:0000269|PubMed:9298824" FT /id="VAR_003592" FT VARIANT 178 FT /note="N -> D (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs1060502855)" FT /evidence="ECO:0000269|PubMed:8878438" FT /id="VAR_078154" FT VARIANT 180 FT /note="F -> C (in HHC1; although the mutant receptor is FT expressed normally at the cell surface it is unresponsive FT with respect to intracellular signaling (MAPK activation) FT to increases in extracellular calcium concentrations; FT dbSNP:rs121909268)" FT /evidence="ECO:0000269|PubMed:17473068" FT /id="VAR_058057" FT VARIANT 185 FT /note="R -> Q (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs104893689)" FT /evidence="ECO:0000269|PubMed:7916660, FT ECO:0000269|PubMed:8636323, ECO:0000269|PubMed:8702647" FT /id="VAR_003593" FT VARIANT 191 FT /note="E -> K (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; dbSNP:rs104893697)" FT /evidence="ECO:0000269|PubMed:8813042, FT ECO:0000269|PubMed:8878438" FT /id="VAR_058058" FT VARIANT 215 FT /note="D -> G (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000269|PubMed:8636323" FT /id="VAR_078155" FT VARIANT 220 FT /note="R -> W (in HHC1; dbSNP:rs1482119762)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078156" FT VARIANT 221 FT /note="P -> L (in HYPOC1; dbSNP:rs397514728)" FT /evidence="ECO:0000269|PubMed:22789683" FT /id="VAR_078157" FT VARIANT 221 FT /note="P -> Q (in HHC1; dbSNP:rs397514728)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058059" FT VARIANT 221 FT /note="P -> S (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:8878438" FT /id="VAR_078158" FT VARIANT 225 FT /note="K -> T (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058060" FT VARIANT 227 FT /note="R -> L (in NSHPT; decreased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization; dbSNP:rs28936684)" FT /evidence="ECO:0000269|PubMed:15572418, FT ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:8675635, FT ECO:0000269|PubMed:8878438" FT /id="VAR_003594" FT VARIANT 227 FT /note="R -> Q (in HHC1; G-protein coupled receptor FT signaling pathway; less markedly impaired relative to FT wild-type than L-227; does not affect cell membrane FT localization; dbSNP:rs28936684)" FT /evidence="ECO:0000269|PubMed:15572418, FT ECO:0000269|PubMed:7726161" FT /id="VAR_003595" FT VARIANT 228 FT /note="E -> K (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078159" FT VARIANT 250 FT /note="E -> K (in dbSNP:rs62269092)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058061" FT VARIANT 271 FT /note="S -> F (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058062" FT VARIANT 297 FT /note="E -> K (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs121909259)" FT /evidence="ECO:0000269|PubMed:27434672, FT ECO:0000269|PubMed:7916660, ECO:0000269|PubMed:8702647" FT /id="VAR_003596" FT VARIANT 336 FT /note="Missing (in NSHPT)" FT /evidence="ECO:0000269|PubMed:14985373" FT /id="VAR_065200" FT VARIANT 339 FT /note="P -> T (mutation found in a patient with primary FT hyperparathyroidism detected at adulthood; inactivating FT mutation; mutant CASR is activated by a higher calcium FT concentrations than the wild-type)" FT /evidence="ECO:0000269|PubMed:20846291" FT /id="VAR_065201" FT VARIANT 354 FT /note="E -> A (in EIG8; patients present juvenile myoclonus FT epilepsy)" FT /evidence="ECO:0000269|PubMed:18756473" FT /id="VAR_060206" FT VARIANT 397 FT /note="G -> R (in HHC1; dbSNP:rs1064794291)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058063" FT VARIANT 459 FT /note="Q -> R (in HHC1; decreased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:19789209" FT /id="VAR_078160" FT VARIANT 465 FT /note="R -> Q (in HHC1; loss-of-function mutation; the FT quantity of the mutant receptor is higher than that of the FT wild-type receptor; dose-response curves show that the FT mutation significantly reduces the sensitivity of the FT receptor to extracellular calcium concentrations; FT dbSNP:rs104893716)" FT /evidence="ECO:0000269|PubMed:16598859" FT /id="VAR_058064" FT VARIANT 509 FT /note="G -> R (in HHC1; dbSNP:rs193922423)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058065" FT VARIANT 549 FT /note="G -> R (in HHC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078161" FT VARIANT 550 FT /note="T -> I (in HHC1; decreased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:21566075" FT /id="VAR_078162" FT VARIANT 551 FT /note="R -> K (in NSHPT; decreased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization; dbSNP:rs1060502861)" FT /evidence="ECO:0000269|PubMed:17555508, FT ECO:0000269|PubMed:27434672" FT /id="VAR_078163" FT VARIANT 553 FT /note="G -> R (in HHC1; dbSNP:rs104893719)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058066" FT VARIANT 555 FT /note="I -> V (in HHC1; dbSNP:rs777646067)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058067" FT VARIANT 557 FT /note="G -> E (in HHC1; Abolished G-protein coupled FT receptor activity)" FT /evidence="ECO:0000269|PubMed:11762699, FT ECO:0000269|PubMed:27434672" FT /id="VAR_012649" FT VARIANT 562 FT /note="C -> Y (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911, FT ECO:0000269|PubMed:19179454" FT /id="VAR_058068" FT VARIANT 565 FT /note="C -> G (in HHC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078164" FT VARIANT 569 FT /note="P -> H (in HYPOC1; increased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:23966241" FT /id="VAR_078165" FT VARIANT 571 FT /note="G -> W (in HHC1; decreased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:26386835" FT /id="VAR_078166" FT VARIANT 582 FT /note="C -> F (in HHC1; dbSNP:rs104893690)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058069" FT VARIANT 582 FT /note="C -> Y (in NSHPT and HHC1; dbSNP:rs104893690)" FT /evidence="ECO:0000269|PubMed:17698911, FT ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:8675635" FT /id="VAR_003597" FT VARIANT 583..1078 FT /note="Missing (in HHC1; impaired homodimerization; FT impaired cell membrane localization)" FT /evidence="ECO:0000269|PubMed:16740594, FT ECO:0000269|PubMed:19179454" FT /id="VAR_078167" FT VARIANT 604 FT /note="E -> K (in HYPOC1; there is a significant leftward FT shift in the concentration response curves for the effects FT of extracellular calcium on both intracellular calcium FT mobilization and MAPK activity; dbSNP:rs104893712)" FT /evidence="ECO:0000269|PubMed:12574188, FT ECO:0000269|PubMed:19179454" FT /id="VAR_058070" FT VARIANT 612 FT /note="F -> S (in HYPOC1; dbSNP:rs104893698)" FT /evidence="ECO:0000269|PubMed:8813042" FT /id="VAR_058071" FT VARIANT 616 FT /note="L -> V (in HYPOC1; does not affect the total FT accumulation of inositol phosphates as a function of FT extracellular calcium concentrations in transfected cells; FT dbSNP:rs104893703)" FT /evidence="ECO:0000269|PubMed:10487661" FT /id="VAR_015414" FT VARIANT 623 FT /note="G -> D (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058072" FT VARIANT 650 FT /note="L -> P (in NSHPT)" FT /evidence="ECO:0000269|PubMed:14985373" FT /id="VAR_065202" FT VARIANT 657 FT /note="S -> Y (in HHC1)" FT /evidence="ECO:0000269|PubMed:8636323" FT /id="VAR_078168" FT VARIANT 661 FT /note="C -> Y (in HHC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078169" FT VARIANT 670 FT /note="G -> E (in NSHPT; dbSNP:rs104893700)" FT /evidence="ECO:0000269|PubMed:9253359" FT /id="VAR_058073" FT VARIANT 670 FT /note="G -> R (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058074" FT VARIANT 680 FT /note="R -> H (in HHC1; dbSNP:rs773146939)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078170" FT VARIANT 681 FT /note="Q -> H (in HYPOC1; dbSNP:rs121909261)" FT /evidence="ECO:0000269|PubMed:8733126" FT /id="VAR_003598" FT VARIANT 681 FT /note="Q -> R (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:22789683" FT /id="VAR_078171" FT VARIANT 686 FT /note="I -> V (in EIG8; patients present juvenile myoclonus FT epilepsy; dbSNP:rs753013993)" FT /evidence="ECO:0000269|PubMed:18756473" FT /id="VAR_060207" FT VARIANT 689 FT /note="V -> M (in NSHPT)" FT /evidence="ECO:0000269|PubMed:14985373" FT /id="VAR_065203" FT VARIANT 697 FT /note="V -> M (in HHC1)" FT /evidence="ECO:0000269|PubMed:21643651" FT /id="VAR_065494" FT VARIANT 707 FT /note="E -> V (in HHC1; decreased protein level)" FT /evidence="ECO:0000269|PubMed:25104082" FT /id="VAR_078172" FT VARIANT 727 FT /note="L -> Q (in HYPOC1; increased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization; dbSNP:rs104893718)" FT /evidence="ECO:0000269|PubMed:16608894, FT ECO:0000269|PubMed:22789683" FT /id="VAR_058075" FT VARIANT 728 FT /note="V -> F (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058076" FT VARIANT 742 FT /note="W -> R (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058077" FT VARIANT 748 FT /note="P -> R (in HHC1)" FT /evidence="ECO:0000269|PubMed:8636323" FT /id="VAR_078173" FT VARIANT 761 FT /note="Missing (in HHC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078174" FT VARIANT 767 FT /note="E -> K (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:15551332" FT /id="VAR_021019" FT VARIANT 773 FT /note="L -> R (in HYPOC1; the mutation shifts the FT concentration-response curve to the left and increases FT maximal activity; dbSNP:rs104893699)" FT /evidence="ECO:0000269|PubMed:9253358" FT /id="VAR_058078" FT VARIANT 774 FT /note="G -> S (in HHC1; decreased G-protein coupled FT receptor signaling pathway; does not affect cell membrane FT localization)" FT /evidence="ECO:0000269|PubMed:25104082" FT /id="VAR_078175" FT VARIANT 788 FT /note="F -> C (in HYPOC1; leftward shift in the FT concentration-response curve for the mutant receptor; cells FT cotransfected with both the wild-type and the mutant FT receptor show an EC(50) similar to the mutant; a FT gain-of-function mutation rendering the receptor more FT sensitive than normal to activation; dbSNP:rs104893701)" FT /evidence="ECO:0000269|PubMed:9661634" FT /id="VAR_058079" FT VARIANT 788 FT /note="F -> L (in HYPOC1; induces a significant shift to FT the left relative to the wild-type protein in the MAPK FT response to increasing extracellular calcium FT concentrations; dbSNP:rs886041537 and dbSNP:rs104893711)" FT /evidence="ECO:0000269|PubMed:12915654" FT /id="VAR_058080" FT VARIANT 795 FT /note="R -> W (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs121909258)" FT /evidence="ECO:0000269|PubMed:19179454, FT ECO:0000269|PubMed:22114145, ECO:0000269|PubMed:7916660, FT ECO:0000269|PubMed:8702647" FT /id="VAR_003599" FT VARIANT 802 FT /note="N -> I (in HYPOC1; increased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:19179454, FT ECO:0000269|PubMed:23169696" FT /id="VAR_078176" FT VARIANT 802 FT /note="N -> S (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs140022350)" FT /evidence="ECO:0000269|PubMed:23169696" FT /id="VAR_078177" FT VARIANT 806 FT /note="F -> S (in HYPOC1; does not produce a significant FT activating effect; decreased cell surface receptor FT expression; dbSNP:rs104893693)" FT /evidence="ECO:0000269|PubMed:8733126, FT ECO:0000269|PubMed:9253358" FT /id="VAR_003600" FT VARIANT 817 FT /note="V -> I (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs1057518933)" FT /evidence="ECO:0000269|PubMed:8878438" FT /id="VAR_078178" FT VARIANT 820 FT /note="S -> F (in HYPOC1; the concentration-response curve FT of the mutant receptor is left-shifted and its EC(50) is FT significantly lower than that of the wild-type; FT dbSNP:rs104893710)" FT /evidence="ECO:0000269|PubMed:12050233" FT /id="VAR_058081" FT VARIANT 830 FT /note="G -> S (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078179" FT VARIANT 832 FT /note="F -> L (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078180" FT VARIANT 832 FT /note="F -> S (in HYPOC1)" FT /evidence="ECO:0000269|PubMed:19179454" FT /id="VAR_078181" FT VARIANT 839 FT /note="I -> T (in HYPOC1; increased G-protein coupled FT receptor signaling pathway)" FT /evidence="ECO:0000269|PubMed:23966241" FT /id="VAR_078182" FT VARIANT 843 FT /note="A -> E (in HYPOC1; some patients have clinical FT features of Bartter syndrome; shifts the FT concentration-response curve of calcium ions to the left; FT dbSNP:rs104893706)" FT /evidence="ECO:0000269|PubMed:12107202, FT ECO:0000269|PubMed:12241879" FT /id="VAR_058082" FT VARIANT 851 FT /note="C -> S (in dbSNP:rs200777304)" FT /evidence="ECO:0000269|PubMed:8733126" FT /id="VAR_003601" FT VARIANT 881 FT /note="F -> L (found in a patient with hypercalciuric FT hypercalcemia; likely pathogenic; mutant CASR has a FT right-shifted dose-response to extracellular calcium FT concentrations; activated by a higher calcium FT concentrations than the wild-type; dbSNP:rs104893704)" FT /evidence="ECO:0000269|PubMed:10843194" FT /id="VAR_058083" FT VARIANT 886 FT /note="R -> W (in HHC1)" FT /evidence="ECO:0000269|PubMed:17698911" FT /id="VAR_058084" FT VARIANT 898 FT /note="R -> Q (in EIG8; dbSNP:rs121909269)" FT /evidence="ECO:0000269|PubMed:18756473" FT /id="VAR_060208" FT VARIANT 951 FT /note="P -> T (in dbSNP:rs4987051)" FT /id="VAR_020220" FT VARIANT 972 FT /note="T -> M (in HHC1; decreased G-protein coupled FT receptor signaling pathway; dbSNP:rs200620134)" FT /evidence="ECO:0000269|PubMed:25292184" FT /id="VAR_078183" FT VARIANT 986 FT /note="A -> S (correlated with high serum level of calcium; FT is also a potential predisposing factor in disorders of FT bone and mineral metabolism; dbSNP:rs1801725)" FT /evidence="ECO:0000269|PubMed:10023897, FT ECO:0000269|PubMed:11161843, ECO:0000269|PubMed:14985373, FT ECO:0000269|PubMed:15531522, ECO:0000269|PubMed:16598859, FT ECO:0000269|PubMed:17555508, ECO:0000269|PubMed:17698911, FT ECO:0000269|PubMed:18756473, ECO:0000269|PubMed:19789209, FT ECO:0000269|PubMed:8636323, ECO:0000269|Ref.5" FT /id="VAR_014450" FT VARIANT 988 FT /note="A -> G (in EIG8; patients present juvenile myoclonus FT epilepsy)" FT /evidence="ECO:0000269|PubMed:18756473" FT /id="VAR_060209" FT VARIANT 988 FT /note="A -> V (in EIG8; patients present juvenile myoclonus FT epilepsy; dbSNP:rs759027000)" FT /evidence="ECO:0000269|PubMed:18756473" FT /id="VAR_060210" FT VARIANT 990 FT /note="R -> G (correlated with low serum level of calcium; FT dbSNP:rs1042636)" FT /evidence="ECO:0000269|PubMed:12050233, FT ECO:0000269|PubMed:14985373, ECO:0000269|PubMed:15531522, FT ECO:0000269|PubMed:15551332, ECO:0000269|PubMed:17698911, FT ECO:0000269|PubMed:18756473, ECO:0000269|PubMed:7759551, FT ECO:0000269|PubMed:8636323, ECO:0000269|Ref.5" FT /id="VAR_020221" FT VARIANT 1011 FT /note="E -> Q (in dbSNP:rs1801726)" FT /evidence="ECO:0000269|PubMed:14985373, FT ECO:0000269|PubMed:15531522, ECO:0000269|PubMed:17698911, FT ECO:0000269|PubMed:19789209, ECO:0000269|PubMed:8636323, FT ECO:0000269|Ref.5" FT /id="VAR_014451" FT MUTAGEN 69 FT /note="R->E: Abolishes G-protein coupled receptor signaling FT pathway." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 102 FT /note="N->I: Abolishes G-protein coupled receptor FT activity." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 145 FT /note="T->A: Abolishes G-protein coupled receptor FT activity." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 147 FT /note="S->A: Nearly abolished G-protein coupled receptor FT activity." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 170 FT /note="S->A: Abolishes G-protein coupled receptor FT activity." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 218 FT /note="Y->S: Abolishes G-protein coupled receptor FT activity." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 297 FT /note="E->I: Abolishes ability to sense calcium or FT magnesium levels." FT /evidence="ECO:0000269|PubMed:27386547" FT MUTAGEN 417 FT /note="S->L: Abolishes G-protein coupled receptor signaling FT pathway." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 458 FT /note="W->A: Decreased G-protein coupled receptor signaling FT pathway." FT /evidence="ECO:0000269|PubMed:27434672" FT MUTAGEN 482 FT /note="C->S,Y: Abolishes ability of agonist AMG 416 to FT activate G-protein-coupled receptor activity." FT /evidence="ECO:0000269|PubMed:26290606" FT CONFLICT 857 FT /note="I -> T (in Ref. 3; BAA09453)" FT /evidence="ECO:0000305" FT CONFLICT 878 FT /note="A -> R (in Ref. 3; BAA09453)" FT /evidence="ECO:0000305" FT CONFLICT 926 FT /note="Q -> R (in Ref. 2; AAA86503)" FT /evidence="ECO:0000305" FT STRAND 22..24 FT /evidence="ECO:0007829|PDB:7M3F" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 31..38 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 40..44 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 51..53 FT /evidence="ECO:0007829|PDB:7SIL" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 65..82 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 85..90 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 93..99 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 104..114 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 116..123 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 125..128 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:7E6T" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:7E6T" FT STRAND 138..142 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 147..159 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 172..175 FT /evidence="ECO:0007829|PDB:5FBK" FT TURN 177..179 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 183..187 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 191..203 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 208..216 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 219..232 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 237..243 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 249..261 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 266..270 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 273..285 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 297..300 FT /evidence="ECO:0007829|PDB:5FBK" FT TURN 303..305 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 308..310 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 311..314 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 318..322 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 330..335 FT /evidence="ECO:0007829|PDB:5FBK" FT TURN 339..341 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 348..356 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 358..360 FT /evidence="ECO:0007829|PDB:5K5T" FT HELIX 374..378 FT /evidence="ECO:0007829|PDB:5K5T" FT STRAND 384..386 FT /evidence="ECO:0007829|PDB:5K5T" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:5K5T" FT HELIX 401..403 FT /evidence="ECO:0007829|PDB:5FBK" FT TURN 407..409 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 416..435 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 441..444 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 445..447 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 452..454 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 457..465 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 468..470 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 472..474 FT /evidence="ECO:0007829|PDB:7DTV" FT STRAND 476..478 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 481..485 FT /evidence="ECO:0007829|PDB:5K5T" FT STRAND 489..496 FT /evidence="ECO:0007829|PDB:5FBK" FT TURN 498..500 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 502..511 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 513..515 FT /evidence="ECO:0007829|PDB:5FBH" FT STRAND 519..523 FT /evidence="ECO:0007829|PDB:5FBK" FT HELIX 525..527 FT /evidence="ECO:0007829|PDB:5FBK" FT TURN 531..533 FT /evidence="ECO:0007829|PDB:5FBK" FT STRAND 550..554 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 556..558 FT /evidence="ECO:0007829|PDB:5K5T" FT STRAND 563..567 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 576..578 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 579..581 FT /evidence="ECO:0007829|PDB:7E6T" FT STRAND 587..591 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 596..600 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 602..604 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 608..610 FT /evidence="ECO:0007829|PDB:7SIL" FT HELIX 611..636 FT /evidence="ECO:0007829|PDB:7M3G" FT TURN 637..639 FT /evidence="ECO:0007829|PDB:7SIL" FT HELIX 641..645 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 650..663 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 664..668 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 669..671 FT /evidence="ECO:0007829|PDB:7SIL" FT TURN 674..678 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 681..696 FT /evidence="ECO:0007829|PDB:7M3G" FT TURN 701..705 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 725..745 FT /evidence="ECO:0007829|PDB:7M3G" FT STRAND 749..753 FT /evidence="ECO:0007829|PDB:7M3G" FT TURN 755..757 FT /evidence="ECO:0007829|PDB:7E6T" FT STRAND 758..766 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 771..793 FT /evidence="ECO:0007829|PDB:7M3G" FT TURN 794..796 FT /evidence="ECO:0007829|PDB:7M3G" FT TURN 800..802 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 803..820 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 822..827 FT /evidence="ECO:0007829|PDB:7M3G" FT TURN 829..831 FT /evidence="ECO:0007829|PDB:7M3F" FT HELIX 834..852 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 854..862 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 863..865 FT /evidence="ECO:0007829|PDB:7M3E" FT TURN 866..868 FT /evidence="ECO:0007829|PDB:7M3E" FT HELIX 869..872 FT /evidence="ECO:0007829|PDB:7M3G" FT HELIX 880..885 FT /evidence="ECO:0007829|PDB:7M3G" SQ SEQUENCE 1078 AA; 120675 MW; D60C57C6C743FC06 CRC64; MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD LKSRPESVEC IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT CNTVSKALEA TLSFVAQNKI DSLNLDEFCN CSEHIPSTIA VVGATGSGVS TAVANLLGLF YIPQVSYASS SRLLSNKNQF KSFLRTIPND EHQATAMADI IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS ELISQYSDEE EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE FWEETFNCHL QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN ISSVETPYID YTHLRISYNV YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD ECGDLVGNYS IINWHLSPED GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREVPFS NCSRDCLAGT RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW SNENHTSCIA KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT PIVKATNREL SYLLLFSLLC CFSSSLFFIG EPQDWTCRLR QPAFGISFVL CISCILVKTN RVLLVFEAKI PTSFHRKWWG LNLQFLLVFL CTFMQIVICV IWLYTAPPSS YRNQELEDEI IFITCHEGSL MALGFLIGYT CLLAAICFFF AFKSRKLPEN FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA ILAASFGLLA CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR RSNVSRKRSS SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ QEQQQQPLTL PQQQRSQQQP RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR NSTHQNSLEA QKSSDTLTRH EPLLPLQCGE TDLDLTVQET GLQGPVGGDQ RPEVEDPEEL SPALVVSSSQ SFVISGGGST VTENVVNS //