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Entry version 176 (07 Sep 2016)
Sequence version 2 (01 Nov 1995)
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Protein

Extracellular calcium-sensing receptor

Gene

CASR

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein levelⁱ

Functionⁱ

Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system.

GO - Molecular functionⁱ

G-protein coupled receptor activity
Source: ProtInc
Traceable author statementⁱ
- 7759551
phosphatidylinositol phospholipase C activity
Source: ProtInc
Traceable author statementⁱ
- 7874174

GO - Biological processⁱ

anatomical structure morphogenesis
Source: ProtInc
Traceable author statementⁱ
- 7916660
calcium ion import
Source: UniProtKB
Inferred from direct assayⁱ
- 20846291
cellular calcium ion homeostasis
Source: ProtInc
Traceable author statementⁱ
- 7874174
chemosensory behavior
Source: ProtInc
Traceable author statementⁱ
- 7759551
detection of calcium ion
Source: ProtInc
Traceable author statementⁱ
- 7759551
G-protein coupled receptor signaling pathway
Source: ProtInc
Traceable author statementⁱ
- 7759551
ossification
Source: ProtInc
Traceable author statementⁱ
- 7874174

Complete GO annotation...

Keywords - Molecular functionⁱ

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

Reactomeⁱ	R-HSA-416476. G alpha (q) signalling events. R-HSA-418594. G alpha (i) signalling events. R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SIGNORⁱ	P41180.

Protein family/group databases

TCDBⁱ

9.A.14.7.2. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Extracellular calcium-sensing receptor Short name: CaSR Alternative name(s): Parathyroid cell calcium-sensing receptor 1 Short name: PCaR1
Gene namesⁱ	Name:CASR Synonyms:GPRC2A, PCAR1
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 3

Organism-specific databases

HGNCⁱ	HGNC:1514. CASR.

HGNCⁱ

HGNC:1514. CASR.

Subcellular locationⁱ

Cell membrane
1 Publication
Manual assertion based on experiment inⁱ
- Ref.10
  "Rab1 small GTP-binding protein regulates cell surface trafficking of the human calcium-sensing receptor."
  Zhuang X., Adipietro K.A., Datta S., Northup J.K., Ray K.
  Endocrinology 151:5114-5123(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.
; Multi-pass membrane protein
1 Publication
Manual assertion based on experiment inⁱ
- Ref.10
  "Rab1 small GTP-binding protein regulates cell surface trafficking of the human calcium-sensing receptor."
  Zhuang X., Adipietro K.A., Datta S., Northup J.K., Ray K.
  Endocrinology 151:5114-5123(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.

Topology

Feature key	Position(s)	Length	Description	Actions
Topological domainⁱ	20 – 612	593	ExtracellularSequence analysis	Add BLAST
Transmembraneⁱ	613 – 635	23	Helical; Name=1Sequence analysis	Add BLAST
Topological domainⁱ	636 – 649	14	CytoplasmicSequence analysis	Add BLAST
Transmembraneⁱ	650 – 670	21	Helical; Name=2Sequence analysis	Add BLAST
Topological domainⁱ	671 – 681	11	ExtracellularSequence analysis	Add BLAST
Transmembraneⁱ	682 – 700	19	Helical; Name=3Sequence analysis	Add BLAST
Topological domainⁱ	701 – 724	24	CytoplasmicSequence analysis	Add BLAST
Transmembraneⁱ	725 – 745	21	Helical; Name=4Sequence analysis	Add BLAST
Topological domainⁱ	746 – 769	24	ExtracellularSequence analysis	Add BLAST
Transmembraneⁱ	770 – 792	23	Helical; Name=5Sequence analysis	Add BLAST
Topological domainⁱ	793 – 805	13	CytoplasmicSequence analysis	Add BLAST
Transmembraneⁱ	806 – 828	23	Helical; Name=6Sequence analysis	Add BLAST
Topological domainⁱ	829 – 836	8	ExtracellularSequence analysis
Transmembraneⁱ	837 – 862	26	Helical; Name=7Sequence analysis	Add BLAST
Topological domainⁱ	863 – 1078	216	CytoplasmicSequence analysis	Add BLAST

GO - Cellular componentⁱ

integral component of plasma membrane
Source: ProtInc
Traceable author statementⁱ
- 7759551
plasma membrane Source: Reactome

Complete GO annotation...

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Hypocalciuric hypercalcemia, familial 1 (HHC1)12 Publications
Manual assertion based on experiment inⁱ
Ref.7
"Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene."
Aida K., Koishi S., Inoue M., Nakazato M., Tawata M., Onaya T.
J. Clin. Endocrinol. Metab. 80:2594-2598(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-61, VARIANT HHC1 ALA-39.
Ref.11
"Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism."
Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., Steinmann B., Levi T., Seidman C.E., Seidman J.G.
Cell 75:1297-1303(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795.
Ref.13
"Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia."
Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E.
Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.
Ref.18
"A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia."
Ward B.K., Stuckey B.G.A., Gutteridge D.H., Laing N.G., Pullan P.T., Ratajczak T.
Hum. Mutat. 10:233-235(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 ARG-174.
Ref.27
"A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia."
Nakayama T., Minato M., Nakagawa M., Soma M., Tobe H., Aoi N., Kosuge K., Sato M., Ozawa Y., Kanmatsuse K., Kokubun S.
Endocrine 15:277-282(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 GLU-557.
Ref.35
"Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor."
Miyashiro K., Kunii I., Manna T.D., de Menezes Filho H.C., Damiani D., Setian N., Hauache O.M.
J. Clin. Endocrinol. Metab. 89:5936-5941(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 PRO-13, CHARACTERIZATION OF VARIANT HHC1 PRO-13.
Ref.38
"Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia."
Pidasheva S., Canaff L., Simonds W.F., Marx S.J., Hendy G.N.
Hum. Mol. Genet. 14:1679-1690(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHC1 SER-11 AND PRO-13, VARIANT ALA-14, CHARACTERIZATION OF VARIANTS HHC1 SER-11 AND PRO-13, CHARACTERIZATION OF VARIANT ALA-14.
Ref.39
"Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism."
Wystrychowski A., Pidasheva S., Canaff L., Chudek J., Kokot F., Wiecek A., Hendy G.N.
J. Clin. Endocrinol. Metab. 90:864-870(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 GLN-227, CHARACTERIZATION OF VARIANT NSHPT LEU-227, CHARACTERIZATION OF VARIANT HHC1 GLN-227.
Ref.40
"Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor."
Leech C., Lohse P., Stanojevic V., Lechner A., Goeke B., Spitzweg C.
Biochem. Biophys. Res. Commun. 342:996-1002(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 GLN-465, CHARACTERIZATION OF VARIANT HHC1 GLN-465, VARIANT SER-986.
Ref.42
"Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status."
Zajickova K., Vrbikova J., Canaff L., Pawelek P.D., Goltzman D., Hendy G.N.
J. Clin. Endocrinol. Metab. 92:2616-2623(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 CYS-180, CHARACTERIZATION OF VARIANT HHC1 CYS-180.
Ref.43
"Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population."
Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L.
J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.
Ref.46
"Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine."
Aparicio Lopez C., Anton-Martin P., Gil-Fournier B., Ramiro-Leon S., Perez-Nanclares G., Perez de Nanclares G., Martinez Menendez B., Castano L.
Eur. J. Pediatr. 171:147-150(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHC1 MET-697.

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.

Hyperparathyroidism, neonatal severe (NSHPT)2 Publications
Manual assertion based on experiment inⁱ
Ref.14
"Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism."
Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V.
J. Clin. Invest. 96:2683-2692(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NSHPT LEU-227 AND TYR-582.
Ref.20
"Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism."
Kobayashi M., Tanaka H., Tsuzuki K., Tsuyuki M., Igaki H., Ichinose Y., Aya K., Nishioka N., Seino Y.
J. Clin. Endocrinol. Metab. 82:2716-2719(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NSHPT GLU-670.

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by severe hypercalcemia, bone demineralization, and failure to thrive usually manifesting in the first 6 months of life. If untreated, NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy.

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	62 – 62	1	R → M in HHC1 and NSHPT; mild. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia." Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E. Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.	VAR_003586
Natural variantⁱ	227 – 227	1	R → L in NSHPT; impaired in their MAPK response to increasing extracellular calcium concentrations; more markedly impaired relative to wild-type than Q-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism." Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V. J. Clin. Invest. 96:2683-2692(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NSHPT LEU-227 AND TYR-582. Ref.39 "Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism." Wystrychowski A., Pidasheva S., Canaff L., Chudek J., Kokot F., Wiecek A., Hendy G.N. J. Clin. Endocrinol. Metab. 90:864-870(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 GLN-227, CHARACTERIZATION OF VARIANT NSHPT LEU-227, CHARACTERIZATION OF VARIANT HHC1 GLN-227. Corresponds to variant rs28936684 [ dbSNP \| Ensembl ].	VAR_003594
Natural variantⁱ	297 – 297	1	E → K in HHC1 and NSHPT. 1 Publication Manual assertion based on experiment inⁱ Ref.11 "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism." Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., Steinmann B., Levi T., Seidman C.E., Seidman J.G. Cell 75:1297-1303(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795.	VAR_003596
Natural variantⁱ	582 – 582	1	C → Y in NSHPT. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism." Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V. J. Clin. Invest. 96:2683-2692(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NSHPT LEU-227 AND TYR-582. Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_003597
Natural variantⁱ	670 – 670	1	G → E in NSHPT. 1 Publication Manual assertion based on experiment inⁱ Ref.20 "Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism." Kobayashi M., Tanaka H., Tsuzuki K., Tsuyuki M., Igaki H., Ichinose Y., Aya K., Nishioka N., Seino Y. J. Clin. Endocrinol. Metab. 82:2716-2719(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NSHPT GLU-670.	VAR_058073

Hypocalcemia, autosomal dominant 1 (HYPOC1)14 Publications
Manual assertion based on experiment inⁱ
Ref.12
"Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation."
Pollak M.R., Brown E.M., Estep H.L., McLaine P.N., Kifor O., Park J., Hebert S.C., Seidman C.E., Seidman J.G.
Nat. Genet. 8:303-307(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 ALA-127.
Ref.16
"Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism."
Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr.
Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.
Ref.17
"A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor."
Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V.
N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.
Ref.19
"Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor."
De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J.
J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.
Ref.21
"Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor."
Watanabe T., Bai M., Lane C.R., Matsumoto S., Minamitani K., Minagawa M., Niimi H., Brown E.M., Yasuda T.
J. Clin. Endocrinol. Metab. 83:2497-2502(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 CYS-788, CHARACTERIZATION OF VARIANT HYPOC1 CYS-788.
Ref.23
"A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia."
Okazaki R., Chikatsu N., Nakatsu M., Takeuchi Y., Ajima M., Miki J., Fujita T., Arai M., Totsuka Y., Tanaka K., Fukumoto S.
J. Clin. Endocrinol. Metab. 84:363-366(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 ASN-47, CHARACTERIZATION OF VARIANT HYPOC1 ASN-47.
Ref.24
"Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis."
Stock J.L., Brown R.S., Baron J., Coderre J.A., Mancilla E., De Luca F., Ray K., Mericq M.V.
J. Clin. Endocrinol. Metab. 84:3036-3040(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 VAL-616, CHARACTERIZATION OF VARIANT HYPOC1 VAL-616.
Ref.29
"A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor."
Nagase T., Murakami T., Tsukada T., Kitamura R., Chikatsu N., Takeo H., Takata N., Yasuda H., Fukumoto S., Tanaka Y., Nagata N., Yamaguchi K., Akatsu T., Yamamoto M.
J. Clin. Endocrinol. Metab. 87:2681-2687(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 PHE-820, CHARACTERIZATION OF VARIANT HYPOC1 PHE-820, VARIANT GLY-990.
Ref.30
"Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene."
Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., Shinohara N., Fujieda K.
J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPOC1 PRO-125 AND GLU-843, CHARACTERIZATION OF VARIANTS HYPOC1 PRO-125 AND GLU-843.
Ref.31
"Association between activating mutations of calcium-sensing receptor and Bartter's syndrome."
Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., Chikatsu N., Fujita T.
Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843.
Ref.32
"Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor."
Tan Y.M., Cardinal J., Franks A.H., Mun H.-C., Lewis N., Harris L.B., Prins J.B., Conigrave A.D.
J. Clin. Endocrinol. Metab. 88:605-610(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 LYS-604, CHARACTERIZATION OF VARIANT HYPOC1 LYS-604.
Ref.33
"Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene."
Hendy G.N., Minutti C., Canaff L., Pidasheva S., Yang B., Nouhi Z., Zimmerman D., Wei C., Cole D.E.C.
J. Clin. Endocrinol. Metab. 88:3674-3681(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 LEU-788, CHARACTERIZATION OF VARIANT HYPOC1 LEU-788.
Ref.37
"A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia."
Uckun-Kitapci A., Underwood L.E., Zhang J., Moats-Staats B.
Am. J. Med. Genet. A 132:125-129(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 LYS-767, VARIANT GLY-990.
Ref.41
"A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone."
Mittelman S.D., Hendy G.N., Fefferman R.A., Canaff L., Mosesova I., Cole D.E., Burkett L., Geffner M.E.
J. Clin. Endocrinol. Metab. 91:2474-2479(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HYPOC1 GLN-727, CHARACTERIZATION OF VARIANT HYPOC1 GLN-727.

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia.

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	47 – 47	1	K → N in HYPOC1; the EC(50) of the mutant is significantly lower than that of wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.23 "A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia." Okazaki R., Chikatsu N., Nakatsu M., Takeuchi Y., Ajima M., Miki J., Fujita T., Arai M., Totsuka Y., Tanaka K., Fukumoto S. J. Clin. Endocrinol. Metab. 84:363-366(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 ASN-47, CHARACTERIZATION OF VARIANT HYPOC1 ASN-47.	VAR_058050
Natural variantⁱ	116 – 116	1	A → T in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.	VAR_003588
Natural variantⁱ	118 – 118	1	N → K in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191. Ref.19 "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor." De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J. J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.	VAR_058051
Natural variantⁱ	125 – 125	1	L → P in HYPOC1; shifts the concentration-response curve of calcium ions to the left. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene." Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., Shinohara N., Fujieda K. J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 PRO-125 AND GLU-843, CHARACTERIZATION OF VARIANTS HYPOC1 PRO-125 AND GLU-843.	VAR_058052
Natural variantⁱ	127 – 127	1	E → A in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.12 "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation." Pollak M.R., Brown E.M., Estep H.L., McLaine P.N., Kifor O., Park J., Hebert S.C., Seidman C.E., Seidman J.G. Nat. Genet. 8:303-307(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 ALA-127.	VAR_003589
Natural variantⁱ	128 – 128	1	F → L in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058053
Natural variantⁱ	131 – 131	1	C → W in HYPOC1; associated with clinical features of Bartter syndrome. 1 Publication Manual assertion based on experiment inⁱ Ref.31 "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome." Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., Chikatsu N., Fujita T. Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843.	VAR_058054
Natural variantⁱ	151 – 151	1	T → M in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 2 Publications Manual assertion based on experiment inⁱ Ref.15 "The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism." Lovlie R., Eiken H.G., Sorheim J.I., Boman H. Hum. Genet. 98:129-133(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FIH MET-151. Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058055
Natural variantⁱ	191 – 191	1	E → K in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058058
Natural variantⁱ	604 – 604	1	E → K in HYPOC1; there is a significant leftward shift in the concentration response curves for the effects of extracellular calcium on both intracellular calcium mobilization and MAPK activity. 1 Publication Manual assertion based on experiment inⁱ Ref.32 "Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor." Tan Y.M., Cardinal J., Franks A.H., Mun H.-C., Lewis N., Harris L.B., Prins J.B., Conigrave A.D. J. Clin. Endocrinol. Metab. 88:605-610(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LYS-604, CHARACTERIZATION OF VARIANT HYPOC1 LYS-604.	VAR_058070
Natural variantⁱ	612 – 612	1	F → S in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058071
Natural variantⁱ	616 – 616	1	L → V in HYPOC1; does not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected cells. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis." Stock J.L., Brown R.S., Baron J., Coderre J.A., Mancilla E., De Luca F., Ray K., Mericq M.V. J. Clin. Endocrinol. Metab. 84:3036-3040(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 VAL-616, CHARACTERIZATION OF VARIANT HYPOC1 VAL-616.	VAR_015414
Natural variantⁱ	681 – 681	1	Q → H in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.	VAR_003598
Natural variantⁱ	727 – 727	1	L → Q in HYPOC1; the mutant receptor demonstrates a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve versus that for the wild-type receptor. 1 Publication Manual assertion based on experiment inⁱ Ref.41 "A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone." Mittelman S.D., Hendy G.N., Fefferman R.A., Canaff L., Mosesova I., Cole D.E., Burkett L., Geffner M.E. J. Clin. Endocrinol. Metab. 91:2474-2479(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 GLN-727, CHARACTERIZATION OF VARIANT HYPOC1 GLN-727.	VAR_058075
Natural variantⁱ	767 – 767	1	E → K in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.37 "A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia." Uckun-Kitapci A., Underwood L.E., Zhang J., Moats-Staats B. Am. J. Med. Genet. A 132:125-129(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LYS-767, VARIANT GLY-990.	VAR_021019
Natural variantⁱ	773 – 773	1	L → R in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 1 Publication Manual assertion based on experiment inⁱ Ref.19 "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor." De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J. J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.	VAR_058078
Natural variantⁱ	788 – 788	1	F → C in HYPOC1; leftward shift in the concentration-response curve for the mutant receptor; cells cotransfected with both the wild-type and the mutant receptor show an EC(50) similar to the mutant; a gain-of-function mutation rendering the receptor more sensitive than normal to activation. 1 Publication Manual assertion based on experiment inⁱ Ref.21 "Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor." Watanabe T., Bai M., Lane C.R., Matsumoto S., Minamitani K., Minagawa M., Niimi H., Brown E.M., Yasuda T. J. Clin. Endocrinol. Metab. 83:2497-2502(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 CYS-788, CHARACTERIZATION OF VARIANT HYPOC1 CYS-788.	VAR_058079
Natural variantⁱ	788 – 788	1	F → L in HYPOC1; induces a significant shift to the left relative to the wild-type protein in the MAPK response to increasing extracellular calcium concentrations. 1 Publication Manual assertion based on experiment inⁱ Ref.33 "Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene." Hendy G.N., Minutti C., Canaff L., Pidasheva S., Yang B., Nouhi Z., Zimmerman D., Wei C., Cole D.E.C. J. Clin. Endocrinol. Metab. 88:3674-3681(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LEU-788, CHARACTERIZATION OF VARIANT HYPOC1 LEU-788.	VAR_058080
Natural variantⁱ	806 – 806	1	F → S in HYPOC1; does not produce a significant activating effect; decreased cell surface receptor expression. 2 Publications Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851. Ref.19 "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor." De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J. J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.	VAR_003600
Natural variantⁱ	820 – 820	1	S → F in HYPOC1; the concentration-response curve of the mutant receptor is left-shifted and its EC(50) is significantly lower than that of the wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.29 "A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor." Nagase T., Murakami T., Tsukada T., Kitamura R., Chikatsu N., Takeo H., Takata N., Yasuda H., Fukumoto S., Tanaka Y., Nagata N., Yamaguchi K., Akatsu T., Yamamoto M. J. Clin. Endocrinol. Metab. 87:2681-2687(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 PHE-820, CHARACTERIZATION OF VARIANT HYPOC1 PHE-820, VARIANT GLY-990.	VAR_058081
Natural variantⁱ	843 – 843	1	A → E in HYPOC1; also in HYPOC1 associated with clinical features of Bartter syndrome; shifts the concentration-response curve of calcium ions to the left. 2 Publications Manual assertion based on experiment inⁱ Ref.30 "Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene." Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., Shinohara N., Fujieda K. J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 PRO-125 AND GLU-843, CHARACTERIZATION OF VARIANTS HYPOC1 PRO-125 AND GLU-843. Ref.31 "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome." Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., Chikatsu N., Fujita T. Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843.	VAR_058082

Epilepsy, idiopathic generalized 8 (EIG8)1 Publication
Manual assertion based on experiment inⁱ
Ref.44
"An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene."
Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A.
Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures.

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	354 – 354	1	E → A in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060206
Natural variantⁱ	686 – 686	1	I → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060207
Natural variantⁱ	898 – 898	1	R → Q in EIG8. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060208
Natural variantⁱ	988 – 988	1	A → G in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060209
Natural variantⁱ	988 – 988	1	A → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060210

Keywords - Diseaseⁱ

Disease mutation, Epilepsy

Organism-specific databases

MalaCardsⁱ	CASR.
MIMⁱ	145980. phenotype. 239200. phenotype. 601198. phenotype. 601199. gene+phenotype. 612899. phenotype.
Orphanetⁱ	428. Autosomal dominant hypocalcemia. 263417. Bartter syndrome with hypocalcemia. 93372. Familial hypocalciuric hypercalcemia type 1. 189466. Familial isolated hypoparathyroidism due to impaired PTH secretion. 417. Neonatal severe primary hyperparathyroidism.
PharmGKBⁱ	PA26097.

Chemistry

ChEMBLⁱ	CHEMBL1878.
DrugBankⁱ	DB01012. Cinacalcet.
GuidetoPHARMACOLOGYⁱ	54.

Polymorphism and mutation databases

BioMutaⁱ	CASR.
DMDMⁱ	1168781.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Signal peptideⁱ	1 – 19	19	Sequence analysis			Add BLAST
Chainⁱ	20 – 1078	1059	Extracellular calcium-sensing receptor		PRO_0000012946	Add BLAST

Amino acid modifications

Feature key	Position(s)	Length	Description
Glycosylationⁱ	90 – 90	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	130 – 130	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	261 – 261	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	287 – 287	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	386 – 386	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	400 – 400	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	446 – 446	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	468 – 468	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	488 – 488	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	541 – 541	1	N-linked (GlcNAc...)Sequence analysis
Glycosylationⁱ	594 – 594	1	N-linked (GlcNAc...)Sequence analysis
Modified residueⁱ	920 – 920	1	PhosphoserineBy similarity Manual assertion inferred from sequence similarity toⁱ UniProtKB:Q9QY96 (CASR_MOUSE)
Modified residueⁱ	1061 – 1061	1	PhosphoserineBy similarity Manual assertion inferred from sequence similarity toⁱ UniProtKB:Q9QY96 (CASR_MOUSE)

Post-translational modificationⁱ

N-glycosylated.2 Publications

Ubiquitinated by RNF19A; which induces proteasomal degradation.1 Publication

Keywords - PTMⁱ

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbⁱ	P41180.
PeptideAtlasⁱ	P41180.
PRIDEⁱ	P41180.

PTM databases

iPTMnetⁱ	P41180.
PhosphoSiteⁱ	P41180.

Expressionⁱ

Tissue specificityⁱ

Expressed in the temporal lobe, frontal lobe, parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, liver, heart, skeletal muscle, placenta.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000036828.
CleanExⁱ	HS_CASR.
ExpressionAtlasⁱ	P41180. baseline and differential.
Genevisibleⁱ	P41180. HS.

Organism-specific databases

HPAⁱ	HPA039686. HPA050335.

Interactionⁱ

Subunit structureⁱ

Interacts with VCP and RNF19A. Interacts with ARRB1 (By similarity).By similarity

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
TMED2	Q15363	3	EBI-4400127,EBI-998485

With

Entry

#Exp.

IntAct

Notes

TMED2

Q15363

EBI-4400127,EBI-998485

Protein-protein interaction databases

BioGridⁱ	107296. 9 interactions.
DIPⁱ	DIP-5975N.
IntActⁱ	P41180. 1 interaction.
MINTⁱ	MINT-201342.
STRINGⁱ	9606.ENSP00000420194.

Chemistry

BindingDBⁱ

P41180.

Structureⁱ

3D structure databases

Select the link destinations:
PDBeⁱ
RCSB PDBⁱ
PDBjⁱ

Links Updated

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
5FBH	X-ray	2.70	A/B	20-541	[»]
5FBK	X-ray	2.10	A/B	20-541	[»]

ProteinModelPortalⁱ

P41180.

SMRⁱ

P41180. Positions 26-493, 603-867.

ModBaseⁱ

Search...

MobiDBⁱ

Search...

Family & Domainsⁱ

Region

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Regionⁱ	880 – 900	21	Interaction with RNF19A			Add BLAST

Sequence similaritiesⁱ

Belongs to the G-protein coupled receptor 3 family.Curated

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG1056. Eukaryota. ENOG410XR6W. LUCA.
HOVERGENⁱ	HBG052876.
InParanoidⁱ	P41180.
KOⁱ	K04612.
PhylomeDBⁱ	P41180.

Family and domain databases

InterProⁱ	IPR001828. ANF_lig-bd_rcpt. IPR000337. GPCR_3. IPR011500. GPCR_3_9-Cys_dom. IPR017978. GPCR_3_C. IPR017979. GPCR_3_CS. IPR028082. Peripla_BP_I. [Graphical view]
Pfamⁱ	PF00003. 7tm_3. 1 hit. PF01094. ANF_receptor. 1 hit. PF07562. NCD3G. 1 hit. [Graphical view]
PRINTSⁱ	PR00248. GPCRMGR.
SUPFAMⁱ	SSF53822. SSF53822. 1 hit.
PROSITEⁱ	PS00979. G_PROTEIN_RECEP_F3_1. 1 hit. PS00980. G_PROTEIN_RECEP_F3_2. 1 hit. PS00981. G_PROTEIN_RECEP_F3_3. 1 hit. PS50259. G_PROTEIN_RECEP_F3_4. 1 hit. [Graphical view]

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket Added to basket

Isoform 1 (identifier: P41180-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD 
        60         70         80         90        100
LKSRPESVEC IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT 
       110        120        130        140        150
CNTVSKALEA TLSFVAQNKI DSLNLDEFCN CSEHIPSTIA VVGATGSGVS 
       160        170        180        190        200
TAVANLLGLF YIPQVSYASS SRLLSNKNQF KSFLRTIPND EHQATAMADI 
       210        220        230        240        250
IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS ELISQYSDEE 
       260        270        280        290        300
EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA 
       310        320        330        340        350
SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE 
       360        370        380        390        400
FWEETFNCHL QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN 
       410        420        430        440        450
ISSVETPYID YTHLRISYNV YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA 
       460        470        480        490        500
DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD ECGDLVGNYS IINWHLSPED 
       510        520        530        540        550
GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREVPFS NCSRDCLAGT 
       560        570        580        590        600
RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW SNENHTSCIA 
       610        620        630        640        650
KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT PIVKATNREL 
       660        670        680        690        700
SYLLLFSLLC CFSSSLFFIG EPQDWTCRLR QPAFGISFVL CISCILVKTN 
       710        720        730        740        750
RVLLVFEAKI PTSFHRKWWG LNLQFLLVFL CTFMQIVICV IWLYTAPPSS 
       760        770        780        790        800
YRNQELEDEI IFITCHEGSL MALGFLIGYT CLLAAICFFF AFKSRKLPEN 
       810        820        830        840        850
FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA ILAASFGLLA 
       860        870        880        890        900
CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR RSNVSRKRSS 
       910        920        930        940        950
SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ QEQQQQPLTL 
       960        970        980        990       1000
PQQQRSQQQP RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR NSTHQNSLEA 
      1010       1020       1030       1040       1050
QKSSDTLTRH QPLLPLQCGE TDLDLTVQET GLQGPVGGDQ RPEVEDPEEL 
      1060       1070 
SPALVVSSSQ SFVISGGGST VTENVVNS

Length:1,078

Mass (Da):120,674

Last modified:November 1, 1995 - v2

Checksum:ⁱ620C57DB1A83E1DB

Isoform 2 (identifier: P41180-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
536-536: E → EPLTFVLSVLQ

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        10         20         30         40         50
MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD 
        60         70         80         90        100
LKSRPESVEC IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT 
       110        120        130        140        150
CNTVSKALEA TLSFVAQNKI DSLNLDEFCN CSEHIPSTIA VVGATGSGVS 
       160        170        180        190        200
TAVANLLGLF YIPQVSYASS SRLLSNKNQF KSFLRTIPND EHQATAMADI 
       210        220        230        240        250
IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS ELISQYSDEE 
       260        270        280        290        300
EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA 
       310        320        330        340        350
SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE 
       360        370        380        390        400
FWEETFNCHL QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN 
       410        420        430        440        450
ISSVETPYID YTHLRISYNV YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA 
       460        470        480        490        500
DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD ECGDLVGNYS IINWHLSPED 
       510        520        530        540        550
GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREPLTF VLSVLQVPFS 
       560        570        580        590        600
NCSRDCLAGT RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW 
       610        620        630        640        650
SNENHTSCIA KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT 
       660        670        680        690        700
PIVKATNREL SYLLLFSLLC CFSSSLFFIG EPQDWTCRLR QPAFGISFVL 
       710        720        730        740        750
CISCILVKTN RVLLVFEAKI PTSFHRKWWG LNLQFLLVFL CTFMQIVICV 
       760        770        780        790        800
IWLYTAPPSS YRNQELEDEI IFITCHEGSL MALGFLIGYT CLLAAICFFF 
       810        820        830        840        850
AFKSRKLPEN FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA 
       860        870        880        890        900
ILAASFGLLA CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR 
       910        920        930        940        950
RSNVSRKRSS SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ 
       960        970        980        990       1000
QEQQQQPLTL PQQQRSQQQP RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR 
      1010       1020       1030       1040       1050
NSTHQNSLEA QKSSDTLTRH QPLLPLQCGE TDLDLTVQET GLQGPVGGDQ 
      1060       1070       1080 
RPEVEDPEEL SPALVVSSSQ SFVISGGGST VTENVVNS

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Length:1,088

Mass (Da):121,772

Checksum:ⁱ0D916FB23151762A

Experimental Info

Feature key	Position(s)	Length	Description
Sequence conflictⁱ	857 – 857	1	I → T in BAA09453 (PubMed:7677761).Curated
Sequence conflictⁱ	878 – 878	1	A → R in BAA09453 (PubMed:7677761).Curated
Sequence conflictⁱ	926 – 926	1	Q → R in AAA86503 (PubMed:7759551).Curated

Natural variant

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	11 – 11	1	L → S in HHC1; demonstrates reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; fails to be inserted in the microsomes and does not undergo proper glycosylation. 1 Publication Manual assertion based on experiment inⁱ Ref.38 "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia." Pidasheva S., Canaff L., Simonds W.F., Marx S.J., Hendy G.N. Hum. Mol. Genet. 14:1679-1690(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 SER-11 AND PRO-13, VARIANT ALA-14, CHARACTERIZATION OF VARIANTS HHC1 SER-11 AND PRO-13, CHARACTERIZATION OF VARIANT ALA-14.	VAR_058046
Natural variantⁱ	13 – 13	1	L → P in HHC1; has a dose-response curve shifted to the right relative to that of wild-type; demonstrates reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; fails to be inserted in the microsomes and does not undergo proper glycosylation. 2 Publications Manual assertion based on experiment inⁱ Ref.35 "Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor." Miyashiro K., Kunii I., Manna T.D., de Menezes Filho H.C., Damiani D., Setian N., Hauache O.M. J. Clin. Endocrinol. Metab. 89:5936-5941(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 PRO-13, CHARACTERIZATION OF VARIANT HHC1 PRO-13. Ref.38 "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia." Pidasheva S., Canaff L., Simonds W.F., Marx S.J., Hendy G.N. Hum. Mol. Genet. 14:1679-1690(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 SER-11 AND PRO-13, VARIANT ALA-14, CHARACTERIZATION OF VARIANTS HHC1 SER-11 AND PRO-13, CHARACTERIZATION OF VARIANT ALA-14.	VAR_058047
Natural variantⁱ	14 – 14	1	T → A Does not demonstrate reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; does not fail to be inserted in the microsomes and does undergo proper glycosylation. 1 Publication Manual assertion based on experiment inⁱ Ref.38 "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia." Pidasheva S., Canaff L., Simonds W.F., Marx S.J., Hendy G.N. Hum. Mol. Genet. 14:1679-1690(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 SER-11 AND PRO-13, VARIANT ALA-14, CHARACTERIZATION OF VARIANTS HHC1 SER-11 AND PRO-13, CHARACTERIZATION OF VARIANT ALA-14.	VAR_058048
Natural variantⁱ	21 – 21	1	G → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058049
Natural variantⁱ	27 – 27	1	Q → R Found in a patient with primary hyperparathyroidism detected at adulthood; mutant CASR is activated by a higher calcium concentrations than the wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.22 "An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium-sensing receptor." Chikatsu N., Fukumoto S., Suzawa M., Tanaka Y., Takeuchi Y., Takeda S., Tamura Y., Matsumoto T., Fujita T. Clin. Endocrinol. (Oxf.) 50:537-543(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-27, CHARACTERIZATION OF VARIANT ARG-27, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.	VAR_065198
Natural variantⁱ	39 – 39	1	P → A in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.7 "Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene." Aida K., Koishi S., Inoue M., Nakazato M., Tawata M., Onaya T. J. Clin. Endocrinol. Metab. 80:2594-2598(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-61, VARIANT HHC1 ALA-39.	VAR_003585
Natural variantⁱ	47 – 47	1	K → N in HYPOC1; the EC(50) of the mutant is significantly lower than that of wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.23 "A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia." Okazaki R., Chikatsu N., Nakatsu M., Takeuchi Y., Ajima M., Miki J., Fujita T., Arai M., Totsuka Y., Tanaka K., Fukumoto S. J. Clin. Endocrinol. Metab. 84:363-366(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 ASN-47, CHARACTERIZATION OF VARIANT HYPOC1 ASN-47.	VAR_058050
Natural variantⁱ	62 – 62	1	R → M in HHC1 and NSHPT; mild. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia." Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E. Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.	VAR_003586
Natural variantⁱ	66 – 66	1	R → C in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia." Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E. Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.	VAR_003587
Natural variantⁱ	100 – 100	1	T → I Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication Manual assertion based on experiment inⁱ Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.	VAR_065199
Natural variantⁱ	116 – 116	1	A → T in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.	VAR_003588
Natural variantⁱ	118 – 118	1	N → K in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191. Ref.19 "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor." De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J. J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.	VAR_058051
Natural variantⁱ	125 – 125	1	L → P in HYPOC1; shifts the concentration-response curve of calcium ions to the left. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene." Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., Shinohara N., Fujieda K. J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 PRO-125 AND GLU-843, CHARACTERIZATION OF VARIANTS HYPOC1 PRO-125 AND GLU-843.	VAR_058052
Natural variantⁱ	127 – 127	1	E → A in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.12 "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation." Pollak M.R., Brown E.M., Estep H.L., McLaine P.N., Kifor O., Park J., Hebert S.C., Seidman C.E., Seidman J.G. Nat. Genet. 8:303-307(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 ALA-127.	VAR_003589
Natural variantⁱ	128 – 128	1	F → L in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058053
Natural variantⁱ	131 – 131	1	C → W in HYPOC1; associated with clinical features of Bartter syndrome. 1 Publication Manual assertion based on experiment inⁱ Ref.31 "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome." Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., Chikatsu N., Fujita T. Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843.	VAR_058054
Natural variantⁱ	138 – 138	1	T → M in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia." Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E. Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.	VAR_003590
Natural variantⁱ	143 – 143	1	G → E in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia." Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E. Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.	VAR_003591
Natural variantⁱ	151 – 151	1	T → M in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 2 Publications Manual assertion based on experiment inⁱ Ref.15 "The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism." Lovlie R., Eiken H.G., Sorheim J.I., Boman H. Hum. Genet. 98:129-133(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FIH MET-151. Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058055
Natural variantⁱ	171 – 171	1	S → N in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058056
Natural variantⁱ	174 – 174	1	L → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia." Ward B.K., Stuckey B.G.A., Gutteridge D.H., Laing N.G., Pullan P.T., Ratajczak T. Hum. Mutat. 10:233-235(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 ARG-174.	VAR_003592
Natural variantⁱ	180 – 180	1	F → C in HHC1; although the mutant receptor is expressed normally at the cell surface it is unresponsive with respect to intracellular signaling (MAPK activation) to increases in extracellular calcium concentrations. 1 Publication Manual assertion based on experiment inⁱ Ref.42 "Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status." Zajickova K., Vrbikova J., Canaff L., Pawelek P.D., Goltzman D., Hendy G.N. J. Clin. Endocrinol. Metab. 92:2616-2623(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 CYS-180, CHARACTERIZATION OF VARIANT HHC1 CYS-180.	VAR_058057
Natural variantⁱ	185 – 185	1	R → Q in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.11 "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism." Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., Steinmann B., Levi T., Seidman C.E., Seidman J.G. Cell 75:1297-1303(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795.	VAR_003593
Natural variantⁱ	191 – 191	1	E → K in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058058
Natural variantⁱ	221 – 221	1	P → Q in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058059
Natural variantⁱ	225 – 225	1	K → T in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058060
Natural variantⁱ	227 – 227	1	R → L in NSHPT; impaired in their MAPK response to increasing extracellular calcium concentrations; more markedly impaired relative to wild-type than Q-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism." Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V. J. Clin. Invest. 96:2683-2692(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NSHPT LEU-227 AND TYR-582. Ref.39 "Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism." Wystrychowski A., Pidasheva S., Canaff L., Chudek J., Kokot F., Wiecek A., Hendy G.N. J. Clin. Endocrinol. Metab. 90:864-870(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 GLN-227, CHARACTERIZATION OF VARIANT NSHPT LEU-227, CHARACTERIZATION OF VARIANT HHC1 GLN-227. Corresponds to variant rs28936684 [ dbSNP \| Ensembl ].	VAR_003594
Natural variantⁱ	227 – 227	1	R → Q in HHC1; impaired in their MAPK response to increasing extracellular calcium concentrations; less markedly impaired relative to wild-type than L-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications Manual assertion based on experiment inⁱ Ref.13 "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia." Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E. Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227. Ref.39 "Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism." Wystrychowski A., Pidasheva S., Canaff L., Chudek J., Kokot F., Wiecek A., Hendy G.N. J. Clin. Endocrinol. Metab. 90:864-870(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 GLN-227, CHARACTERIZATION OF VARIANT NSHPT LEU-227, CHARACTERIZATION OF VARIANT HHC1 GLN-227.	VAR_003595
Natural variantⁱ	250 – 250	1	E → K.1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011. Corresponds to variant rs62269092 [ dbSNP \| Ensembl ].	VAR_058061
Natural variantⁱ	271 – 271	1	S → F in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058062
Natural variantⁱ	297 – 297	1	E → K in HHC1 and NSHPT. 1 Publication Manual assertion based on experiment inⁱ Ref.11 "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism." Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., Steinmann B., Levi T., Seidman C.E., Seidman J.G. Cell 75:1297-1303(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795.	VAR_003596
Natural variantⁱ	336 – 336	1	Missing Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication Manual assertion based on experiment inⁱ Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.	VAR_065200
Natural variantⁱ	339 – 339	1	P → T Mutation found in a patient with primary hyperparathyroidism detected at adulthood; inactivating mutation; mutant CASR is activated by a higher calcium concentrations than the wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.45 "A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia." Hannan F.M., Nesbit M.A., Christie P.T., Lissens W., Van der Schueren B., Bex M., Bouillon R., Thakker R.V. Clin. Endocrinol. (Oxf.) 73:715-722(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-339, CHARACTERIZATION OF VARIANT THR-339, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.	VAR_065201
Natural variantⁱ	354 – 354	1	E → A in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060206
Natural variantⁱ	397 – 397	1	G → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058063
Natural variantⁱ	465 – 465	1	R → Q in HHC1; loss-of-function mutation; the quantity of the mutant receptor is higher than that of the wild-type receptor; dose-response curves show that the mutation significantly reduces the sensitivity of the receptor to extracellular calcium concentrations. 1 Publication Manual assertion based on experiment inⁱ Ref.40 "Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor." Leech C., Lohse P., Stanojevic V., Lechner A., Goeke B., Spitzweg C. Biochem. Biophys. Res. Commun. 342:996-1002(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 GLN-465, CHARACTERIZATION OF VARIANT HHC1 GLN-465, VARIANT SER-986.	VAR_058064
Natural variantⁱ	509 – 509	1	G → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011. Corresponds to variant rs193922423 [ dbSNP \| Ensembl ].	VAR_058065
Natural variantⁱ	553 – 553	1	G → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058066
Natural variantⁱ	555 – 555	1	I → V in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058067
Natural variantⁱ	557 – 557	1	G → E in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.27 "A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia." Nakayama T., Minato M., Nakagawa M., Soma M., Tobe H., Aoi N., Kosuge K., Sato M., Ozawa Y., Kanmatsuse K., Kokubun S. Endocrine 15:277-282(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 GLU-557.	VAR_012649
Natural variantⁱ	562 – 562	1	C → Y in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058068
Natural variantⁱ	582 – 582	1	C → F in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058069
Natural variantⁱ	582 – 582	1	C → Y in NSHPT. 2 Publications Manual assertion based on experiment inⁱ Ref.14 "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism." Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V. J. Clin. Invest. 96:2683-2692(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NSHPT LEU-227 AND TYR-582. Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_003597
Natural variantⁱ	604 – 604	1	E → K in HYPOC1; there is a significant leftward shift in the concentration response curves for the effects of extracellular calcium on both intracellular calcium mobilization and MAPK activity. 1 Publication Manual assertion based on experiment inⁱ Ref.32 "Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor." Tan Y.M., Cardinal J., Franks A.H., Mun H.-C., Lewis N., Harris L.B., Prins J.B., Conigrave A.D. J. Clin. Endocrinol. Metab. 88:605-610(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LYS-604, CHARACTERIZATION OF VARIANT HYPOC1 LYS-604.	VAR_058070
Natural variantⁱ	612 – 612	1	F → S in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor." Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V. N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.	VAR_058071
Natural variantⁱ	616 – 616	1	L → V in HYPOC1; does not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected cells. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis." Stock J.L., Brown R.S., Baron J., Coderre J.A., Mancilla E., De Luca F., Ray K., Mericq M.V. J. Clin. Endocrinol. Metab. 84:3036-3040(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 VAL-616, CHARACTERIZATION OF VARIANT HYPOC1 VAL-616.	VAR_015414
Natural variantⁱ	623 – 623	1	G → D in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058072
Natural variantⁱ	650 – 650	1	L → P Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication Manual assertion based on experiment inⁱ Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.	VAR_065202
Natural variantⁱ	670 – 670	1	G → E in NSHPT. 1 Publication Manual assertion based on experiment inⁱ Ref.20 "Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism." Kobayashi M., Tanaka H., Tsuzuki K., Tsuyuki M., Igaki H., Ichinose Y., Aya K., Nishioka N., Seino Y. J. Clin. Endocrinol. Metab. 82:2716-2719(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NSHPT GLU-670.	VAR_058073
Natural variantⁱ	670 – 670	1	G → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058074
Natural variantⁱ	681 – 681	1	Q → H in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.	VAR_003598
Natural variantⁱ	686 – 686	1	I → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060207
Natural variantⁱ	689 – 689	1	V → M Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication Manual assertion based on experiment inⁱ Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.	VAR_065203
Natural variantⁱ	697 – 697	1	V → M in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.46 "Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine." Aparicio Lopez C., Anton-Martin P., Gil-Fournier B., Ramiro-Leon S., Perez-Nanclares G., Perez de Nanclares G., Martinez Menendez B., Castano L. Eur. J. Pediatr. 171:147-150(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 MET-697.	VAR_065494
Natural variantⁱ	727 – 727	1	L → Q in HYPOC1; the mutant receptor demonstrates a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve versus that for the wild-type receptor. 1 Publication Manual assertion based on experiment inⁱ Ref.41 "A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone." Mittelman S.D., Hendy G.N., Fefferman R.A., Canaff L., Mosesova I., Cole D.E., Burkett L., Geffner M.E. J. Clin. Endocrinol. Metab. 91:2474-2479(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 GLN-727, CHARACTERIZATION OF VARIANT HYPOC1 GLN-727.	VAR_058075
Natural variantⁱ	728 – 728	1	V → F in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058076
Natural variantⁱ	742 – 742	1	W → R in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058077
Natural variantⁱ	767 – 767	1	E → K in HYPOC1. 1 Publication Manual assertion based on experiment inⁱ Ref.37 "A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia." Uckun-Kitapci A., Underwood L.E., Zhang J., Moats-Staats B. Am. J. Med. Genet. A 132:125-129(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LYS-767, VARIANT GLY-990.	VAR_021019
Natural variantⁱ	773 – 773	1	L → R in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 1 Publication Manual assertion based on experiment inⁱ Ref.19 "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor." De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J. J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.	VAR_058078
Natural variantⁱ	788 – 788	1	F → C in HYPOC1; leftward shift in the concentration-response curve for the mutant receptor; cells cotransfected with both the wild-type and the mutant receptor show an EC(50) similar to the mutant; a gain-of-function mutation rendering the receptor more sensitive than normal to activation. 1 Publication Manual assertion based on experiment inⁱ Ref.21 "Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor." Watanabe T., Bai M., Lane C.R., Matsumoto S., Minamitani K., Minagawa M., Niimi H., Brown E.M., Yasuda T. J. Clin. Endocrinol. Metab. 83:2497-2502(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 CYS-788, CHARACTERIZATION OF VARIANT HYPOC1 CYS-788.	VAR_058079
Natural variantⁱ	788 – 788	1	F → L in HYPOC1; induces a significant shift to the left relative to the wild-type protein in the MAPK response to increasing extracellular calcium concentrations. 1 Publication Manual assertion based on experiment inⁱ Ref.33 "Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene." Hendy G.N., Minutti C., Canaff L., Pidasheva S., Yang B., Nouhi Z., Zimmerman D., Wei C., Cole D.E.C. J. Clin. Endocrinol. Metab. 88:3674-3681(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LEU-788, CHARACTERIZATION OF VARIANT HYPOC1 LEU-788.	VAR_058080
Natural variantⁱ	795 – 795	1	R → W in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.11 "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism." Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., Steinmann B., Levi T., Seidman C.E., Seidman J.G. Cell 75:1297-1303(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795.	VAR_003599
Natural variantⁱ	806 – 806	1	F → S in HYPOC1; does not produce a significant activating effect; decreased cell surface receptor expression. 2 Publications Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851. Ref.19 "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor." De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J. J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.	VAR_003600
Natural variantⁱ	820 – 820	1	S → F in HYPOC1; the concentration-response curve of the mutant receptor is left-shifted and its EC(50) is significantly lower than that of the wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.29 "A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor." Nagase T., Murakami T., Tsukada T., Kitamura R., Chikatsu N., Takeo H., Takata N., Yasuda H., Fukumoto S., Tanaka Y., Nagata N., Yamaguchi K., Akatsu T., Yamamoto M. J. Clin. Endocrinol. Metab. 87:2681-2687(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 PHE-820, CHARACTERIZATION OF VARIANT HYPOC1 PHE-820, VARIANT GLY-990.	VAR_058081
Natural variantⁱ	843 – 843	1	A → E in HYPOC1; also in HYPOC1 associated with clinical features of Bartter syndrome; shifts the concentration-response curve of calcium ions to the left. 2 Publications Manual assertion based on experiment inⁱ Ref.30 "Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene." Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., Shinohara N., Fujieda K. J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 PRO-125 AND GLU-843, CHARACTERIZATION OF VARIANTS HYPOC1 PRO-125 AND GLU-843. Ref.31 "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome." Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., Chikatsu N., Fujita T. Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843.	VAR_058082
Natural variantⁱ	851 – 851	1	C → S.1 Publication Manual assertion based on experiment inⁱ Ref.16 "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism." Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr. Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.	VAR_003601
Natural variantⁱ	881 – 881	1	F → L Probable disease-associated mutation found in a patient with hypercalciuric hypercalcemia; mutant CASR has a right-shifted dose-response to extracellular calcium concentrations; activated by a higher calcium concentrations than the wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.26 "Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor." Carling T., Szabo E., Bai M., Ridefelt P., Westin G., Gustavsson P., Trivedi S., Hellman P., Brown E.M., Dahl N., Rastad J. J. Clin. Endocrinol. Metab. 85:2042-2047(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPERCALCIURIC HYPERCALCEMIA LEU-881, CHARACTERIZATION OF VARIANT HYPERCALCIURIC HYPERCALCEMIA LEU-881.	VAR_058083
Natural variantⁱ	886 – 886	1	R → W in HHC1. 1 Publication Manual assertion based on experiment inⁱ Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.	VAR_058084
Natural variantⁱ	898 – 898	1	R → Q in EIG8. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060208
Natural variantⁱ	951 – 951	1	P → T. Corresponds to variant rs4987051 [ dbSNP \| Ensembl ].	VAR_020220
Natural variantⁱ	986 – 986	1	A → S Associated with high serum level of calcium; is also a potential predisposing factor in disorders of bone and mineral metabolism. 8 Publications Manual assertion based on experiment inⁱ Ref.5 SeattleSNPs variation discovery resource Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-986; GLY-990 AND GLU-1011. Ref.25 "A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations." Cole D.E.C., Peltekova V.D., Rubin L.A., Hawker G.A., Vieth R., Liew C.C., Hwang D.M., Evrovski J., Hendy G.N. Lancet 353:112-115(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-986, ASSOCIATION WITH SERUM LEVEL OF CALCIUM. Ref.28 "Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene." Cole D.E.C., Vieth R., Trang H.M., Wong B.Y.-L., Hendy G.N., Rubin L.A. Mol. Genet. Metab. 72:168-174(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-986, ASSOCIATION WITH SERUM LEVEL OF CALCIUM, PREDISPOSING FACTOR IN DISORDERS OF BONE AND MINERAL METABOLISM. Ref.34 "Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor." Scillitani A., Guarnieri V., De Geronimo S., Muscarella L.A., Battista C., D'Agruma L., Bertoldo F., Florio C., Minisola S., Hendy G.N., Cole D.E.C. J. Clin. Endocrinol. Metab. 89:5634-5638(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-986; GLY-990 AND GLU-1011, ASSOCIATION WITH SERUM LEVEL OF CALCIUM. Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM. Ref.40 "Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor." Leech C., Lohse P., Stanojevic V., Lechner A., Goeke B., Spitzweg C. Biochem. Biophys. Res. Commun. 342:996-1002(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHC1 GLN-465, CHARACTERIZATION OF VARIANT HHC1 GLN-465, VARIANT SER-986. Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011. Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY. Corresponds to variant rs1801725 [ dbSNP \| Ensembl ].	VAR_014450
Natural variantⁱ	988 – 988	1	A → G in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060209
Natural variantⁱ	988 – 988	1	A → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.	VAR_060210
Natural variantⁱ	990 – 990	1	R → G Associated with low serum level of calcium. 8 Publications Manual assertion based on experiment inⁱ Ref.2 "Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs." Garrett J.E., Capuano I.V., Hammerland L.G., Hung B.C., Brown E.M., Hebert S.C., Nemeth E.F., Fuller F. J. Biol. Chem. 270:12919-12925(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT GLY-990. Ref.5 SeattleSNPs variation discovery resource Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-986; GLY-990 AND GLU-1011. Ref.29 "A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor." Nagase T., Murakami T., Tsukada T., Kitamura R., Chikatsu N., Takeo H., Takata N., Yasuda H., Fukumoto S., Tanaka Y., Nagata N., Yamaguchi K., Akatsu T., Yamamoto M. J. Clin. Endocrinol. Metab. 87:2681-2687(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 PHE-820, CHARACTERIZATION OF VARIANT HYPOC1 PHE-820, VARIANT GLY-990. Ref.34 "Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor." Scillitani A., Guarnieri V., De Geronimo S., Muscarella L.A., Battista C., D'Agruma L., Bertoldo F., Florio C., Minisola S., Hendy G.N., Cole D.E.C. J. Clin. Endocrinol. Metab. 89:5634-5638(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-986; GLY-990 AND GLU-1011, ASSOCIATION WITH SERUM LEVEL OF CALCIUM. Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM. Ref.37 "A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia." Uckun-Kitapci A., Underwood L.E., Zhang J., Moats-Staats B. Am. J. Med. Genet. A 132:125-129(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPOC1 LYS-767, VARIANT GLY-990. Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011. Ref.44 "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene." Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A. Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY. Corresponds to variant rs1042636 [ dbSNP \| Ensembl ].	VAR_020221
Natural variantⁱ	1011 – 1011	1	Q → E Associated with high serum level of calcium. 4 Publications Manual assertion based on experiment inⁱ Ref.5 SeattleSNPs variation discovery resource Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-986; GLY-990 AND GLU-1011. Ref.34 "Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor." Scillitani A., Guarnieri V., De Geronimo S., Muscarella L.A., Battista C., D'Agruma L., Bertoldo F., Florio C., Minisola S., Hendy G.N., Cole D.E.C. J. Clin. Endocrinol. Metab. 89:5634-5638(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-986; GLY-990 AND GLU-1011, ASSOCIATION WITH SERUM LEVEL OF CALCIUM. Ref.36 "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications." Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J. J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM. Ref.43 "Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population." Nissen P.H., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L. J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011. Corresponds to variant rs1801726 [ dbSNP \| Ensembl ].	VAR_014451

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Alternative sequenceⁱ	536 – 536	1	E → EPLTFVLSVLQ in isoform 2. 1 Publication Manual assertion based on opinion inⁱ Ref.2 "Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs." Garrett J.E., Capuano I.V., Hammerland L.G., Hung B.C., Brown E.M., Hebert S.C., Nemeth E.F., Fuller F. J. Biol. Chem. 270:12919-12925(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT GLY-990.		VSP_002035

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X81086 Genomic DNA. Translation: CAA56990.1. U20759 mRNA. Translation: AAA86503.1. U20760 mRNA. Translation: AAA86504.1. D50855 mRNA. Translation: BAA09453.1. S83176 mRNA. Translation: AAB46873.1. S79217 mRNA. Translation: AAB35262.2. S81755 mRNA. Translation: AAD14370.1. S68032 Genomic DNA. Translation: AAB29413.2. Sequence problems. S68033 Genomic DNA. Translation: AAB29414.1. S68036 Genomic DNA. Translation: AAB29415.1. DQ088967 Genomic DNA. Translation: AAY68221.1. BC104999 mRNA. Translation: AAI05000.1. BC112236 mRNA. Translation: AAI12237.1.
CCDSⁱ	CCDS3010.1. [P41180-1] CCDS54632.1. [P41180-2]
PIRⁱ	A56715. B56715.
RefSeqⁱ	NP_000379.2. NM_000388.3. [P41180-1] NP_001171536.1. NM_001178065.1. [P41180-2]
UniGeneⁱ	Hs.435615.

Genome annotation databases

Ensemblⁱ	ENST00000296154; ENSP00000296154; ENSG00000036828. ENST00000490131; ENSP00000418685; ENSG00000036828.
GeneIDⁱ	846.
KEGGⁱ	hsa:846.
UCSCⁱ	uc003eev.5. human. [P41180-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Cross-referencesⁱ

Web resourcesⁱ

SeattleSNPs

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X81086 Genomic DNA. Translation: CAA56990.1. U20759 mRNA. Translation: AAA86503.1. U20760 mRNA. Translation: AAA86504.1. D50855 mRNA. Translation: BAA09453.1. S83176 mRNA. Translation: AAB46873.1. S79217 mRNA. Translation: AAB35262.2. S81755 mRNA. Translation: AAD14370.1. S68032 Genomic DNA. Translation: AAB29413.2. Sequence problems. S68033 Genomic DNA. Translation: AAB29414.1. S68036 Genomic DNA. Translation: AAB29415.1. DQ088967 Genomic DNA. Translation: AAY68221.1. BC104999 mRNA. Translation: AAI05000.1. BC112236 mRNA. Translation: AAI12237.1.
CCDSⁱ	CCDS3010.1. [P41180-1] CCDS54632.1. [P41180-2]
PIRⁱ	A56715. B56715.
RefSeqⁱ	NP_000379.2. NM_000388.3. [P41180-1] NP_001171536.1. NM_001178065.1. [P41180-2]
UniGeneⁱ	Hs.435615.

3D structure databases

Select the link destinations:
PDBeⁱ
RCSB PDBⁱ
PDBjⁱ

Links Updated

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
5FBH	X-ray	2.70	A/B	20-541	[»]
5FBK	X-ray	2.10	A/B	20-541	[»]

ProteinModelPortalⁱ

P41180.

SMRⁱ

P41180. Positions 26-493, 603-867.

ModBaseⁱ

Search...

MobiDBⁱ

Search...

Protein-protein interaction databases

BioGridⁱ	107296. 9 interactions.
DIPⁱ	DIP-5975N.
IntActⁱ	P41180. 1 interaction.
MINTⁱ	MINT-201342.
STRINGⁱ	9606.ENSP00000420194.

Chemistry

BindingDBⁱ	P41180.
ChEMBLⁱ	CHEMBL1878.
DrugBankⁱ	DB01012. Cinacalcet.
GuidetoPHARMACOLOGYⁱ	54.

Protein family/group databases

TCDBⁱ	9.A.14.7.2. the g-protein-coupled receptor (gpcr) family.
GPCRDBⁱ	Search...

PTM databases

iPTMnetⁱ	P41180.
PhosphoSiteⁱ	P41180.

Polymorphism and mutation databases

BioMutaⁱ	CASR.
DMDMⁱ	1168781.

Proteomic databases

PaxDbⁱ	P41180.
PeptideAtlasⁱ	P41180.
PRIDEⁱ	P41180.

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000296154; ENSP00000296154; ENSG00000036828. ENST00000490131; ENSP00000418685; ENSG00000036828.
GeneIDⁱ	846.
KEGGⁱ	hsa:846.
UCSCⁱ	uc003eev.5. human. [P41180-1]

Organism-specific databases

CTDⁱ	846.
GeneCardsⁱ	CASR.
H-InvDB	HIX0163457.
HGNCⁱ	HGNC:1514. CASR.
HPAⁱ	HPA039686. HPA050335.
MalaCardsⁱ	CASR.
MIMⁱ	145980. phenotype. 239200. phenotype. 601198. phenotype. 601199. gene+phenotype. 612899. phenotype.
neXtProtⁱ	NX_P41180.
Orphanetⁱ	428. Autosomal dominant hypocalcemia. 263417. Bartter syndrome with hypocalcemia. 93372. Familial hypocalciuric hypercalcemia type 1. 189466. Familial isolated hypoparathyroidism due to impaired PTH secretion. 417. Neonatal severe primary hyperparathyroidism.
PharmGKBⁱ	PA26097.
GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1056. Eukaryota. ENOG410XR6W. LUCA.
HOVERGENⁱ	HBG052876.
InParanoidⁱ	P41180.
KOⁱ	K04612.
PhylomeDBⁱ	P41180.

Enzyme and pathway databases

Reactomeⁱ	R-HSA-416476. G alpha (q) signalling events. R-HSA-418594. G alpha (i) signalling events. R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SIGNORⁱ	P41180.

Miscellaneous databases

GeneWikiⁱ	Calcium-sensing_receptor.
GenomeRNAiⁱ	846.
PROⁱ	P41180.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000036828.
CleanExⁱ	HS_CASR.
ExpressionAtlasⁱ	P41180. baseline and differential.
Genevisibleⁱ	P41180. HS.

Family and domain databases

InterProⁱ	IPR001828. ANF_lig-bd_rcpt. IPR000337. GPCR_3. IPR011500. GPCR_3_9-Cys_dom. IPR017978. GPCR_3_C. IPR017979. GPCR_3_CS. IPR028082. Peripla_BP_I. [Graphical view]
Pfamⁱ	PF00003. 7tm_3. 1 hit. PF01094. ANF_receptor. 1 hit. PF07562. NCD3G. 1 hit. [Graphical view]
PRINTSⁱ	PR00248. GPCRMGR.
SUPFAMⁱ	SSF53822. SSF53822. 1 hit.
PROSITEⁱ	PS00979. G_PROTEIN_RECEP_F3_1. 1 hit. PS00980. G_PROTEIN_RECEP_F3_2. 1 hit. PS00981. G_PROTEIN_RECEP_F3_3. 1 hit. PS50259. G_PROTEIN_RECEP_F3_4. 1 hit. [Graphical view]
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ

CASR_HUMAN

Accessionⁱ

Primary (citable) accession number: P41180
Secondary accession number(s): Q13912

Q4PJ19

Entry historyⁱ

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	November 1, 1995
Last modified:	September 7, 2016
This is version 176 of the entry and version 2 of the sequence. [Complete history]

Entry statusⁱ

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries
Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

Similar proteinsⁱ

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:

100%	UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%	UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%	UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

UniProtKB

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UniRef

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Supporting data

UniProtKB - P41180 (CASR_HUMAN)

UniProt

P41180 - CASR_HUMAN

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Extracellular calcium-sensing receptor

CASR

Select a section on the left to see content.

<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>Provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.</p><p><a href='../manual/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>Provides information on the location and the topology of the mature protein in the cell.</p><p><a href='../manual/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>Provides information on the disease(s) and phenotype(s) associated with a protein.</p><p><a href='../manual/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Chemistry

Polymorphism and mutation databases

<p>Describes post-translational modifications (PTMs) and/or processing events.</p><p><a href='../manual/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>Provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.</p><p><a href='../manual/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>Provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.</p><p><a href='../manual/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry

<p>Provides information on the tertiary and secondary structure of a protein.</p><p><a href='../manual/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>Provides information on sequence similarities with other proteins and the domain(s) present in a protein.</p><p><a href='../manual/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>Provides information about the sequence similarity with other proteins.</p><p><a href='../manual/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>Displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.</p><p><a href='../manual/sequences_section' target='_top'>More...</a></p>Sequences (2)i

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

<p>Is used to point to information related to entries and found in data collections other than UniProtKB.</p><p><a href='../manual/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>Provides links to various web resources that are relevant for a specific protein.</p><p><a href='../manual/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

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Chemistry

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

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Phylogenomic databases

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Miscellaneous databases

Gene expression databases

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<p>Provides general information on the entry.</p><p><a href='../manual/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>Contains any relevant information that doesn’t fit in any other defined sections</p><p><a href='../manual/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequences (2)ⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ