Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

CASR

contributors: mct - updated : 27-08-2020

HGNC name	calcium-sensing receptor
HGNC id	1514

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine parathyroid       predominantly Homo sapiens Nervous brain limbic system hippocampus     Homo sapiens   brain forebrain cerebral lobe frontal lobe   Homo sapiens   brain forebrain cerebral lobe parietal lobe   Homo sapiens   brain hindbrain cerebellum     Homo sapiens Urinary kidney       highly Homo sapiens

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
	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

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
	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

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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 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
	System Type Disorder Pubmed cancer urinary   targeting CASR might be beneficial in patients with bone metastatic in renal cell carcinoma (RCC) with a high CASR expression.

ANIMAL & CELL MODELS