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CaS receptor

Family: Calcium-sensing receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Allosteric Regulators
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
References
Gene and Protein Information
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1078 3q21-q24 CASR calcium-sensing receptor 39
Mouse 7 1079 16 B3 Casr calcium-sensing receptor 50
Rat 7 1079 11q22 Casr calcium-sensing receptor 85
Previous and Unofficial Names
CaSR
CasR
CaR
HHC
HHC1
FHH
NSHPT
GPRC2A
hypocalciuric hypercalcemia 1
severe neonatal hyperparathyroidism
Calcium-sensing receptor (hypocalciuric hypercalcemia 1 severe neonatal hyperparathyroidism)
Calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism)
PCaR1
calcium-sensing receptor
extracellular calcium-sensing receptor
parathyroid Cell calcium-sensing receptor
cation sensing receptor
Database Links
ChEMBL Target 282 (Hs), 10489 (Rn)
DrugBank Target 565 (Hs)
Ensembl ENSG00000036828 (Hs), ENSMUSG00000051980 (Mm), ENSRNOG00000002265 (Rn)
Entrez Gene 846 (Hs), 12374 (Mm), 24247 (Rn)
GeneCards CASR (Hs)
GenitoUrinary Development Molecular Anatomy Project Casr (Mm)
HomoloGene 332 (Hs)
Human Protein Reference Database 03122 (Hs)
InterPro P41180 (Hs), Q9QY96 (Mm), P48442 (Rn)
KEGG Gene hsa:846 (Hs), mmu:12374 (Mm), rno:24247 (Rn)
OMIM 601199 (Hs)
Orphanet Gene ORPHA119185 (Hs)
PharmGKB Gene PA26097 (Hs)
PhosphoSitePlus P41180 (Hs), Q9QY96 (Mm), P48442 (Rn)
Protein Ontology (PRO) PRO:000005058 (Hs)
RefSeq Nucleotide NM_000388 (Hs), NM_013803 (Mm), NM_016996 (Rn)
RefSeq Protein NP_000379 (Hs), NP_038831 (Mm), NP_058692 (Rn)
TreeFam ENSG00000036828 (Hs), ENSMUSG00000051980 (Mm), ENSRNOG00000002265 (Rn)
UniGene Hs. 435615 (Hs)
UniProt P41180 (Hs), Q9QY96 (Mm), P48442 (Rn)
Wikipedia CaS receptor
Calcium-sensing receptors
Search for 3D structures on the PDB
Search by keyword: Calcium-sensing receptors CaS receptor Search by accession number: P48442, P41180, Q9QY96
Natural/Endogenous Ligand(s)
Ca2+
Mg2+
Amino-acid rank order of potency
L-phenylalanine, L-tryptophan, L-histidine > L-alanine > L-serine, L-proline, L-glutamic acid > L-aspartic acid (not L-lysine, L-arginine, L-leucine and L-isoleucine)  [29]
Cation rank order of potency
Gd3+ > Ca2+ > Mg2+  [13]
Polyamine rank order of potency
spermine > spermidine > putrescine  [81]
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
neomycin Rn Full agonist 4.0 pKd 85
spermine Hs Full agonist 3.5 pKd 81
Ca2+ Rn Full agonist 2.5 pKd 85
Ca2+ Mm Full agonist 2.5 pKd 79
Ca2+ Hs Full agonist 2.4 pKd 39
Mg2+ Rn Partial agonist 2.4 pKd 11,85
View species-specific agonist tables
Agonist Comments
Other aminoglycosides show agonist activity [85].

Bovine data is available on a number of other ligands including: polyarginine (and other polycations) (pKd 7) ([14]), Gd3+ and other lanthanides (pKd 4.3-4.9) ([12-13]), neomycin (and other aminoglycosides) (pKd 6.9).
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
NPS 2143 Hs Antagonist 7.1 – 7.4 pIC50 69,108
2-methyl-3-phenethyl-3H-pyrimidin-4-one (cmp 2H) Hs Antagonist 7.0 pIC50 95
compound (S)-3h [PMID:15686947] Hs Antagonist 6.9 pIC50 108
N-[(1R, 2R)-2-(1-naphthalen-1-ylethylamino)cyclohexyl]-4-(trifluoromethyl) benzenesulfonamide Rn Antagonist 5.3 pIC50 53
1-arylmethylpyrrolidin-2-yl ethanol amine Rn Antagonist 4.3 pIC50 41
View species-specific antagonist tables
Antagonist Comments
There have been few, if any, studies evaluating whether these are competitive or noncompetitive antagonists. The binding site for polycationic (type 1) CaR agonists, such as calcium or gadolinium, are almost certainly in a different location from that of these antagonists, with the former being predominantly in the amino-terminal extracellular domain and the latter in the transmembrane domains. However, the binding site for the calcimimetic (type 2) CaR activators, at a minimum, overlaps with that of the antagonists. [15,45]
Allosteric Regulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
NPS R-568 Hs Positive 6.5 pKd 70
calindol Hs Positive 6.0 – 6.5 pKd 52
L-tryptophan Hs Positive 2.6 – 4.4 pKd 28-29
AC265347 Hs Positive 7.6 – 8.1 pEC50 59
cinacalcet Hs Positive 7.3 pEC50 71
calindol Hs Positive 6.5 pEC50 78
calhex 231 Hs Negative 6.4 pIC50 77
Allosteric Regulator Comments
Note that aromatic amino acids and calcimimetics are ineffective in the absence of Ca2+.

N1-Arylsulfonyl-N2-(1-aryl)ethyl-3-phenylpropane-1,2-diamines [30] and cinacalcet [67,94] are also allosteric regulators, but do not have associated affinity values.

Activity is also shown by other aromatic amino acids e.g. L-phe, L-tyr, L-his

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family 		Adenylate cyclase inhibition
Phospholipase C stimulation
Phospholipase D stimulation
Comments:  In [48], activation of PLD by the CaR takes place through a direct mechanism involving G12/G13. In some cases, inhibition of adenylate cyclase appears to be indirect, occurring by a calcium sensing receptor-mediated increase in the cytosolic calcium concentration, which then inhibits a calcium-sensitive isoform of adenylate cyclase, see below [31].
References:  17,25,48,54,68
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family
G protein (identity unknown) 		Adenylate cyclase stimulation
Potassium channel
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  In addition to the transducers and effectors noted above, the calcium sensing receptor also activates a nonselective cation channel [111], MAPK pathways, e.g., ERK1/2 [3,55,64] , p38 MAPK [60], JNK [21], PI-3K [97], PI-4K [47], Rho [80] and the epidermal growth factor receptor [61].
References:  3,24,31,54-55,64,110-111
Tissue Distribution
Embryonic astrocytes, astrocytomas and meningiomas.
Species:  Human
Technique:  Northern blotting, RT-PCR and Western blotting.
References:  20
Osteosarcoma cell line, MG-63.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  105
Osteoblastic cells, SaOS-2.
Species:  Human
Technique:  Western blotting.
References:  18
Colon cancer cells, Caco-2.
Species:  Human
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  51
Lens epithelial cells.
Species:  Human
Technique:  Northern blotting, RT-PCR and immunocytochemistry.
References:  22
Pancreatic islet and insulinoma cells.
Species:  Human
Technique:  RT-PCR.
References:  49,82
C-cells.
Species:  Human
Technique:  in situ hybridization.
References:  37
Pancreatic islet and insulinoma cells
Species:  Human
Technique:  immunocytochemistry.
References:  56
Pancreatic acinar and duct cells.
Pancreatic cancer cells, Capan-1.
Species:  Human
Technique:  RT-PCR and immunocytochemistry.
References:  82
Breast ductal cells.
Species:  Human
Technique:  Northern blotting, RT-PCR and immunocytochemistry.
References:  26
Gastrinoma cells.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  49
Breast cancer cell lines, MCF-7 and MDA-MB-231.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  92
Gastric mucosal epithelial cells.
Species:  Human
Technique:  Immunocytochemistry and Western blotting.
References:  89
Pituitary.
Species:  Human
Technique:  Northern blotting.
References:  62
Keratinocytes.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  35
Thyroid c-cells.
Species:  Human
Technique:  RT-PCR.
References:  40
Placental villi (cytotrophoblasts and synctiotrophoblasts), trophoblast columns.
Species:  Human
Technique:  Northern blotting, RT-PCR, in situ hybridisation and immunocytochemistry.
References:  8
Monocytes.
Species:  Human
Technique:  Northern blotting.
References:  75
Minor salivary gland.
Species:  Human
Technique:  Northern blotting.
References:  44
Prostate cancer cells, PC-3 and LnCaP.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  109
Ovarian surface cells.
Species:  Human
Technique:  Northern and Western blotting.
References:  63
Promyelocytic leukemia cells, HL-60.
Species:  Human
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  107
Myeloma cells, U266, IM-9 and RPM18226.
Species:  Human
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  106
Medullary thyroid cancer, normal and adenomatous parathyroid, normal and adenomatous pituitary.
Species:  Human
Technique:  RT-PCR.
References:  62
Colon.
Species:  Human
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  96
Parathyroid.
Species:  Human
Technique:  Northern blotting.
References:  39
Osteoblasts, osteoclasts, osteocytes and chondrocytes.
Species:  Mouse
Technique:  In situ hybridisation and immunocytochemistry.
References:  18
Osteoblastic cell line, MC3T3-E1.
Species:  Mouse
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  104
Bone marrow stromal cell line, ST-2.
Species:  Mouse
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  103
Monocytic cell line, J774.
Species:  Mouse
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  34
Pituitary cell line, AtT-20.
Species:  Mouse
Technique:  Northern blotting, RT-PCR and immunocytochemistry.
References:  34
Skin.
Species:  Mouse
Technique:  RT-PCR and immunocytochemistry.
References:  57
Parathyroid.
Species:  Mouse
Technique:  immunocytochemistry.
References:  46
Kidney.
Species:  Mouse
Technique:  Immunocytochemistry and Western blotting.
References:  46
Breast.
Species:  Mouse
Technique:  RNAse protection and immunocytochemistry.
References:  99
Mesangial cells.
Species:  Mouse
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  58
Osteoblast, osteocyte and osteoclast.
Species:  Rat
Technique:  immunocytochemistry.
References:  33
Osteoblast, osteocyte and osteoclast.
Species:  Rat
Technique:  RT-PCR.
References:  33
Fibroblasts.
Species:  Rat
Technique:  Northern blot.
References:  64
Oligodendrocytes.
Species:  Rat
Technique:  RT-PCR, immunocytochemistry and Western blotting.
References:  22
Kidney.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  84,86
C-cells.
Species:  Rat
Technique:  Northern blot.
References:  37,40
Stomach.
Species:  Rat
Technique:  Northern blot.
References:  27
Medullary thyroid cancer cell line (rMTC44-2).
Species:  Rat
Technique:  RT-PCR.
References:  40
Heart.
Species:  Rat
Technique:  RT-PCR.
References:  101
Sensory nerve.
Species:  Rat
Technique:  Western blotting.
References:  102
Pancreas, adrenal medulla, testis, multiple brain regions.
Species:  Rat
Technique:  immunocytochemistry.
References:  65
Small and large intestine.
Species:  Rat
Technique:  immunocytochemistry.
References:  19,65
Kidney.
Species:  Rat
Technique:  immunocytochemistry.
References:  65,86
Kidney inner medullary collecting duct.
Species:  Rat
Technique:  Western blotting.
References:  93
Kidney proximal tubule.
Species:  Rat
Technique:  immunocytochemistry.
References:  86
Stomach.
Species:  Rat
Technique:  immunocytochemistry.
References:  27,65
Parathyroid and kidney.
Species:  Rat
Technique:  Ribonuclease protection assay.
References:  10
Liver.
Species:  Rat
Technique:  Immunocytochemistry and Western blotting.
References:  16
Heart.
Species:  Rat
Technique:  Western blotting.
References:  65
Osteoblasts, osteoclasts and osteocytes.
Species:  Rat
Technique:  RT-PCR.
References:  33
Osteoblasts, osteoclasts, osteocytes and chondrocytes.
Species:  Rat
Technique:  immunocytochemistry.
References:  18
Thyroid c-cells.
Species:  Rat
Technique:  Northern blotting, in situ hybridisation and immunocytochemistry.
References:  40
Fibroblasts.
Species:  Rat
Technique:  Northern and Western blotting.
References:  64
Testicular cancer cell-line H-500.
Species:  Rat
Technique:  RT-PCR, Western blot, immunocytochemistry.
References:  90
Small and large intestine.
Species:  Rat
Technique:  Northern blot.
References:  19
Oligodendrocytes.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  23
Oligodendrocytes.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  23
Microglia.
Species:  Rat
Technique:  Northern blot, RT-PCR and immunocytochemistry.
References:  24
Testicular cancer cell (H-500).
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  90
Multiple brain regions.
Species:  Rat
Technique:  in situ hybridization.
References:  88
Osteoblast, osteocyte, osteocyte and chondrocyte.
Species:  Rat
Technique:  in situ hybridization.
References:  18
C-cells.
Species:  Rat
Technique:  immunocytochemistry.
References:  37
Kidney.
Species:  Rat
Technique:  immunocytochemistry.
References:  65
Microglia.
Species:  Rat
Technique:  Northern blotting, RT-PCR, immunocytochemistry and Western blotting.
References:  24
Tissue Distribution Comments
A variety of techniques--Northern blotting, RT-PCR, immunocytochemistry and Western blotting--were used to identify the calcium sensing receptor in the receptor distribution studies. Lack of availability of some human tissues, such as kidney, have so far precluded a comprehensive tissue survery for expression of the human calcium sensing receptor in humans.
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Effects of agonists/allosteric regulators on human calcium sensing receptor-transfected HEK 293 cells.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in cytosolic calcium concentration, inhibition of adenylate cyclase, stimulation of inositol phosphate generation, activation of MAPK.
References:  5,17,55
Effects of agonists/allosteric regulators on rat calcium sensing receptor-transfected CHO cells.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Stimulation of inositol phosphate generation, inhibition of adenylate cyclase.
References:  53,77
Measurement of cytosolic calcium concentration, adenylate cyclase activity, inositol phosphate generatation and activity of MAPK.
Species:  Mouse
Tissue:  AtT-20 cells.
Response measured:  Increase in intracellular Ca2+, inhibition of adenylate cyclase, stimulation of inositol phosphate generation, activation of MAPK.
References:  34
Functional Assay Comments
In addition to these two calcium sensing receptor transfected cell systems, measurement of the same responses AtT-20 cells [53] have also proven to be useful test systems.
Physiological Functions
Inhibition of proliferation of colonic crypt cells.
Species:  Human
Tissue:  Colon cancer cell line.
References:  51
Stimulation of non-selective cation channel.
Species:  Rat
Tissue:  Hippocampal neurons.
References:  111
Inhibition of PTH secretion and parathyroid cellular proliferation.
Species:  Human
Tissue:  Parathyroid glands or cells.
References:  67,70
Inhibition of PTH secretion and parathyroid cellular proliferation.
Species:  Rat
Tissue:  Parathyroid glands or cells.
References:  100
Inhibition of PTH-stimulated phosphate excretion in the proximal tubule.
Species:  Mouse
Tissue:  Microdissected in vitro tubule preparations.
References:  4
Inhibition of vasopressin-stimulated reabsorption of water in the renal inner medullary collecting duct.
Species:  Rat
Tissue:  Microdissected in vitro tubule preparations.
References:  93
Stimulation of PTHrP secretion in vitro.
Species:  Human
Tissue:  Prostate cell line.
References:  91
Stimulation of calcitonin secretion from thyroidal C-cells.
Species:  Rat
Tissue:  C-cell cell line rMTC44-2.
References:  40
Stimulation of calcitonin secretion from thyroidal C-cells.
Species:  Human
Tissue:  C-cell cell lines.
References:  37
Promotion of differentiation of keratinocytes.
Species:  Mouse
Tissue:  Primary cultures of keratinocytes, intact mouse epidermis in vivo.
References:  57,72,98
Stimulation of secretion of ACTH.
Species:  Mouse
Tissue:  Studies using the murine AtT-20 cell line.
References:  36
Stimulation of secretion of ACTH.
Species:  Human
Tissue:  In vivo.
References:  43
Inhibition of PTH secretion and parathyroid cellular proliferation.
Species:  Mouse
Tissue:  Parathyroid glands or cells.
References:  46
Inhibition of renal tubular reabsorption of calcium and magnesium in the renal thick ascending limb.
Species:  Mouse
Tissue:  Microdissected in vitro tubule preparations.
References:  7,32,66
Stimulation of PTHrP secretion in vitro.
Species:  Human
Tissue:  Breast and prostate cancer cell lines.
References:  91-92
Stimulation of PTHrP secretion in vitro.
Species:  Rat
Tissue:  Testicular cancer cells line H-500.
References:  90
Stimulation of calcitonin secretion from thyroidal C-cells.
Species:  Mouse
Tissue:  In vivo.
References:  38
Inhibition of PTHrP secretion in vitro and in vivo.
Species:  Mouse
Tissue:  Breast epithelial cells.
References:  99
Regulation of hematopoietic cell retention in bone marrow.
Species:  Mouse
Tissue:  Hematopoietic stem cells.
References:  1
Inhibition of colonic fluid secretion.
Species:  Rat
Tissue:  Perfused colon crypts.
References:  42
Stimulation of expression of cyclooxygenase COX-2.
Species:  Human
Tissue:  Jaw cyst fibroblasts.
References:  74
Regulation of secretion of BMP-2 and Noggin.
Species:  Human
Tissue:  18Co colonic myofibroblasts.
References:  76
Regulation in intracellular pH.
Species:  Mouse
Tissue:  In vitro perfused cells of the medullary thick ascending limb.
References:  2
Regulation of expression/secretion of chemokines (CXCL-9, CXCL-10 and MCP-3).
Species:  Mouse
Tissue:  GnRH neurons.
References:  6
Stimulation of gastric acid secretion.
Species:  Mouse
Tissue:  Gastric glands in vitro.
References:  83
Modulation of chondrocyte differentiation.
Species:  Mouse
Tissue:  Cultured chondrocyte cells.
References:  87
Physiological Consequences of Altering Gene Expression
Absent expression of calcium-sensing receptor in calcium receptor knockout mice removes the tonic inhibitory action of extracellular calcium on PTH secretion and parathyroid cellular proliferation and impairs keratinocyte differentiation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  46,57,72
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002896 abnormal bone mineralization PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000678 abnormal parathyroid gland morphology PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002980 abnormal postural reflex PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0001504 abnormal posture PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0001438 aphagia PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0003195 calcinosis PMID: 15347804 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0001304 cataracts PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)		 MGI:1351351  MP:0001304 cataracts PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0001265 decreased body size PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0001262 decreased body weight PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000063 decreased bone density PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0002905 decreased circulating parathyroid hormone level PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)		 MGI:1351351  MP:0002905 decreased circulating parathyroid hormone level PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0001429 dehydration PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000060 delayed bone ossification PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0003112 enlarged parathyroid gland PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000194 hypercalcemia PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000194 hypercalcemia PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0001566 hyperphosphatemia PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)		 MGI:1351351  MP:0001566 hyperphosphatemia PMID: 15347804 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0000195 hypocalcemia PMID: 15347804 
Casr+|CasrNuf CasrNuf/Casr+
either: (involves: 102/Ei * 102/H * C3H/He) or (involves: 102/Ei * C3H/He * C3H/HeH)		 MGI:1351351  MP:0000195 hypocalcemia PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002986 hypocalciuria PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002986 hypocalciuria PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0002986 hypocalciuria PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000198 hypophosphatemia PMID: 11517179 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0002902 hypophosphaturia PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0010092 increased circulating magnesium level PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0010092 increased circulating magnesium level PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002904 increased circulating parathyroid hormone level PMID: 7493018 
Casr+|Casrtm1Ces Casrtm1Ces/Casr+
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002904 increased circulating parathyroid hormone level PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002608 increased hematocrit PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0001846 increased inflammatory response PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0003408 increased width of hypertrophic chondrocyte zone PMID: 11517179 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0000069 kyphoscoliosis PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0005202 lethargy PMID: 7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0003199 muscle calcification PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0003114 pigmented parathyroid gland PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0001732 postnatal growth retardation PMID: 7493018 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0002082 postnatal lethality PMID: 11517179  7493018 
CasrNuf CasrNuf/CasrNuf
involves: 102/Ei * C3H/He		 MGI:1351351  MP:0002083 premature death PMID: 15347804 
Casrtm1Ces Casrtm1Ces/Casrtm1Ces
involves: 129X1/SvJ * Black Swiss		 MGI:1351351  MP:0003116 rickets PMID: 11517179 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Bartter syndrome with hypocalcemia
OMIM:  601199
Orphanet:  263417
References: 
Mutations not determined
Disease:  Neonatal severe primary hyperparathyroidism
OMIM:  239200
Orphanet:  417
References: 
Mutations not determined
Disease:  Familial hypocalciuric hypercalcemia type 1
OMIM:  145980
Orphanet:  93372
References: 
Mutations not determined
Disease:  Familial isolated hypoparathyroidism due to impaired PTH secretion
Orphanet:  189466
References: 
Mutations not determined
Biologically Significant Variants
Calcium-sensing receptor expressed in differentiating keratinocytes that lacks exon 5 and has been suggested to exert a dominant negative action on the full length receptor, although some other data suggest that it may harbor some intrinsic biological activity.
Type:  Splice variants.
Species:  Mouse
References:  57,72-73
Calcium sensing receptor expressed in placental cytotrophoblasts and parathyroid gland that lacks exon 3. Its function is unknown.
Type:  Splice variants.
Species:  Human
References:  9

REFERENCES

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To cite this database page, please use the following:

Daniel Bikle, Hans Bräuner-Osborne, Edward M. Brown, Arthur Conigrave, Dolores Shoback.
Calcium-sensing receptors: CaS receptor. Last modified on 28/02/2013. Accessed on 20/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=54.


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