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FLASH GENE
Symbol CASR contributors: mct - updated : 18-09-2013
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
    DNA
    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
    Physical map
    GPR156 3q13.33 G protein-coupled receptor 156 LOC116064 3q13.33 hypothetical protein LOC116064 FSTL1 3q13.33 follistatin-like 1 NDUFB4 3q13.33 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 4, 15kDa HGD 3q21-q23 homogentisate 1,2-dioxygenase (homogentisate oxidase) MGC23920 GTF2E1 3q21-q24 general transcription factor IIE, polypeptide 1, alpha 56kDa KIAA1006 3q13.33 general transcription factor IIE, polypeptide 1, alpha 56kDa POLQ 3q13.31 polymerase (DNA directed), theta LOC51725 3q21.1 muscle disease-related protein HCLS1 3q13 hematopoietic cell-specific Lyn substrate 1 GOLGB1 3q13 golgi autoantigen, golgin subfamily b, macrogolgin (with transmembrane signal), 1 KIAA0036 3q21.1 golgi autoantigen, golgin subfamily b, macrogolgin (with transmembrane signal), 1 EAF2 3q21.1 ELL associated factor 2 SLC15A2 3p14.3-p14.1 solute carrier family 15 (H+/peptide transporter), member 2 MGC50831 3q21.1 hypothetical protein MGC50831 CD86 3q21 CD86 antigen (CD28 antigen ligand 2, B7-2 antigen) CASR 3q21-q24 calcium-sensing receptor (hypocalciuric hypercalcemia 1, severe neonatal hyperparathyroidism) LOC391570 3 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP) CSTA 3q21 cystatin A (stefin A) LOC131076 3q21.1 hypothetical LOC131076 E2IG5 3q21.1 growth and transformation-dependent protein WDR5B 3q21.1 WD repeat domain 5B KPNA1 3q21 karyopherin alpha 1 (importin alpha 5) BAL 3q13-q21 B aggressive lymphoma gene LOC151636 FLJ40597 3q21.1 hypothetical protein FLJ40597 LOC339881 3q21.1 similar to eukaryotic initiation factor 4B KIAA1268 3q21.1 KIAA1268 protein HSPBAP1 3q21 HSPB (heat shock 27kDa) associated protein 1 DIRC2 3q21.1 disrupted in renal carcinoma 2 SEMA5B 3q21.1 sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5B PDIR 3q21.1 for protein disulfide isomerase-related SEC22L2 3q21.1 SEC22 vesicle trafficking protein-like 2 (S. cerevisiae) ADCY5 3q13.2-q21 adenylate cyclase 5 PTPLB 3q21.1 protein tyrosine phosphatase-like (proline instead of catalytic arginine), member b MYLK 3q21 myosin, light polypeptide kinase FLJ12892 3q21.2 hypothetical protein FLJ12892 ROPN1 3q21.2 ropporin, rhophilin associated protein 1 HAPIP q21.1-q21.2 huntingtin-associated protein interacting protein (duo)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 4924 120.7 1078 - 1995 7673400
    6 splicing 5011 - 1088 - 1995 7673400
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   predominantly
    Nervousbrainlimbic systemhippocampus   Homo sapiens
     brainforebraincerebral lobefrontal lobe  Homo sapiens
     brainforebraincerebral lobeparietal lobe  Homo sapiens
     brainhindbraincerebellum   Homo sapiens
    Urinarykidney    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    interspecies homolog to murine Casr/Gprc2a
    Homologene
    FAMILY
  • G-protein coupled receptor 3 family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text Ca2+ homeostasis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • cell & other
    REGULATION
    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
    ASSOCIATED DISORDERS
    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
    tumoral        
    silenced by genetic and epigenetic mechanisms in unfavorable neuroblastomas
    constitutional     --over  
    in inflammatory states, such as that associated with obesity
    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
    ANIMAL & CELL MODELS