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Symbol CASR contributors: mct - updated : 27-08-2020
HGNC name calcium-sensing receptor
HGNC id 1514
Corresponding disease
EIG8 idiopathic generalized epilepsy-8
HHC1 hypercalcemia hypocalciuric, familial, benign 1
HPT2 hypoparathyroidism 2
HYPOCA hypocalcemia with hyperphosphatemia and low PTH levels
HYPOCAB hypocalcemia severe, with Bartter-like syndrome
NSHPT neonatal severe hyperparathyroidism
Location 3q13.33      Physical location : 121.902.529 - 122.005.343
Synonym name
  • parathyroid cell Ca(2+)-sensing receptor 1
  • extracellular calcium-sensing receptor
  • Synonym symbol(s) FHH, HHC, GPRC2A, NSHPT, PCAR1, CAR, MGC138441, hCAR
    TYPE functioning gene
    STRUCTURE 32.55 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure promoters (P1 and P2) are transactivated by GCM 2 (Canaff 2009)
    MAPPING cloned Y linked Y status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 4924 120.7 1078 - 1995 7673400
    6 splicing 5011 - 1088 - 1995 7673400
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   predominantly Homo sapiens
    Nervousbrainlimbic systemhippocampus   Homo sapiens
     brainforebraincerebral lobefrontal lobe  Homo sapiens
     brainforebraincerebral lobeparietal lobe  Homo sapiens
     brainhindbraincerebellum   Homo sapiens
    Urinarykidney   highly Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • a signal peptide
  • a large N terminal extracellular ligand binding domain including clusters of acidic AAs ressembling the site of low affinity Ca++ binding proteins
  • a seven transmembrane-spanning segment
  • a C terminal intracytoplasmic tail, with a cellular sorting signal encoded by 51 AAs in the carboxyl tail containing a PEST-like motif, contributing to receptor entry into late endosomes or lysosomal compartments for possible degradation
  • conjugated GlycoP
    mono polymer homomer , dimer
    interspecies homolog to murine Casr/Gprc2a
  • G-protein coupled receptor 3 family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text at the plasma membrane as a homodimer, and dimerized in the ER
    basic FUNCTION
  • functioning as a sensor for parathyroid and kidney to determine the extracellular calcium concentration and thus helps to maintain a stable calcium concentration
  • activating phospholipase C
  • possibility of involvement of CASR in pathophysiology of epileptic disorders
  • putatively involved in the regulation of insulin release
  • can regulate parathyroid hormone gene expression in heterologous cells
  • regulates extracellular calcium ion homeostasis by controlling the rate of parathyroid hormone secretion from the parathyroid gland and the rate of calcium re-absorption by the kidney
  • plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation
  • key role for CASR-induced phospholipase C activation and the release of intracellular calcium
  • in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis
  • key role in normal epidermal development
  • specifically modulates nuclear Ca(2+) signalling through the IP3 receptors pathway
  • essential role in systemic calcium homeostasis through its ability to sense small changes in circulating calcium concentration and to couple this information to intracellular signaling pathways that influence parathyroid hormone secretion
  • role in other cellular functions including the control of cellular proliferation, differentiation and apoptosis
  • contributes to maintain homeostatic levels of extracellular calcium
  • controls other cellular activities such as proliferation and migration, particularly in cells not related to extracellular calcium homeostasis
  • CASR and GPR68 reciprocally inhibit signaling through each other in central neurons, but strong intracellular acidification impairs CASR function, and potentiates GPR68 function
  • is an important component in the mechanism of bone metastasis in renal cell carcinoma (RCC)
  • importance of CASR in the regulation of vascular tone and blood pressure
  • G protein-coupled receptor that plays a key role in calcium homeostasis, by sensing free calcium levels in blood and regulating parathyroid hormone secretion in response
    text Ca2+ homeostasis
    a component
    small molecule
  • modified by PTH
  • interacts directly with KCNJ10 and KCNJ15 and can decrease their currents, which in turn could reduce recycling of K(+) for the basolateral Na(+)-K(+)-ATPase and thereby contribute to inhibition of Na(+) reabsorption
  • interacting with TRPV5 (activation of CASR stimulates the activity of the epithelial Ca2+ channel TRPV5)
  • interplay between the CASR and testin in the regulation of CASR-mediated Rho signalling with possible effects on the cytoskeleton
  • recognition of extracellular Ca2+ through CASR activates the NLRP3 inflammasome
  • CASR interacts with GPR39 and thereby regulates its activity
  • CASR interferes with TGFB1-dependent SMAD2 phosphorylation and induces its proteasomal degradation, resulting in a decrease of TGFB1-dependent transcriptional activity
  • might regulate TGFB1-dependent cellular responses mediated by TGFB1 signaling inhibition
  • the kidney expresses a CASR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner
  • cell & other
    inhibited by disruptions of endogenous SAR1A1 function, attenuates cell surface expression of CASR
    Other transactivation of the CASR promoter by GCM2 completely abolished in the presence of the dominant-negative mutant GCM2
    corresponding disease(s) HHC1 , HPT2 , NSHPT , HYPOCA , HYPOCAB , EIG8
    related resource CASR DB Calcium Sensing Receptor Locus Mutation Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    by elevated Ca2+(o) concentrations, such as those found near resorbing bone, produces an especially strong chemoattractant effect on bone metastatic breast cancer cells toward the Ca2+-rich environment
    silenced by genetic and epigenetic mechanisms in unfavorable neuroblastomas
    constitutional     --over  
    in inflammatory states, such as that associated with obesity
    tumoral     --over  
    in lung cancer tissues with bone metastasis, higher than that in non-metastatic lung cancer tissues
    Susceptibility to chronic pancreatitis
    Variant & Polymorphism SNP higher in a healthy group with the S986S genotype
    Candidate gene
  • is one of the candidate genes explaining individual predisposition to calcium nephrolithiasis
  • Marker
    Therapy target
    targeting CASR might be beneficial in patients with bone metastatic in renal cell carcinoma (RCC) with a high CASR expression.