CASR calcium-sensing receptor [Homo sapiens (human)] - Gene

Summary

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Official Symbol: CASRprovided by HGNC
Official Full Name: calcium-sensing receptorprovided by HGNC
Primary source: HGNC:1514
See related: Ensembl:ENSG00000036828; HPRD:03122; MIM:601199; Vega:OTTHUMG00000159491
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CAR; FHH; FIH; HHC; EIG8; HHC1; NSHPT; PCAR1; GPRC2A
Summary: The protein encoded by this gene is a G protein-coupled receptor that is expressed in the parathyroid hormone (PTH)-producing chief cells of the parathyroid gland, and the cells lining the kidney tubule. It senses small changes in circulating calcium concentration and couples this information to intracellular signaling pathways that modify PTH secretion or renal cation handling, thus this protein plays an essential role in maintaining mineral ion homeostasis. Mutations in this gene cause familial hypocalciuric hypercalcemia, familial, isolated hypoparathyroidism, and neonatal severe primary hyperparathyroidism. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 3q13

Sequence :: Chromosome: 3; NC_000003.11 (121902530..122005344)

See CASR in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

report of 2 novel CASR mutations affecting the same amino acid (p.N802); one causes autosomal dominant hypocalcemia and the other atypical hypocalciuric hypercalcemia; the asparagine at amino acid position 802 appears to be essential for activity of CASR protein and is implicated in mechanism of CASR signaling
Title: Two novel mutations of the calcium-sensing receptor gene affecting the same amino acid position lead to opposite phenotypes and reveal the importance of p.N802 on receptor activity.
Upregulated expression & enhanced function of CaSR in pulmonary artery smooth myocytes are involved in the development of sustained pulmonary vasoconstriction & pulmonary vascular remodeling in patients with idiopathic pulmonary hypertension.
Title: Dihydropyridine Ca(2+) channel blockers increase cytosolic [Ca(2+)] by activating Ca(2+)-sensing receptors in pulmonary arterial smooth muscle cells.
Three mutations (G(670)R, P(748)R, and L(773)R) altered the binding affinity of allosteric modulators to the CaSR, and 3 mutations (V(817)I, L(773)R, and E(767)K) altered the cooperativity between the allosteric modulator and Ca(2+)(o).
Title: Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators.
Downregulation of the CaSR gene by hypermethylation is associated with neuroblastomas.
Title: The calcium-sensing receptor is silenced by genetic and epigenetic mechanisms in unfavorable neuroblastomas and its reactivation induces ERK1/2-dependent apoptosis.
Two CASR gene-activating mutations have been identified in two families with autosomal dominant hypocalcemia.
Title: CASR gene activating mutations in two families with autosomal dominant hypocalcemia.
CaSR is functionally expressed in the T cells, the activated CaSR contributes to the cytokine secretion through the partial MAPK and NF-kappaB pathways.
Title: Expression of the calcium sensing receptor in human peripheral blood T lymphocyte and its contribution to cytokine secretion through MAPKs or NF-κB pathways.
CaR and Cav-1 co-localize on the plasma membrane in HUVECs and CaR-induced Ca(2+) influx is down-regulated by binding with Cav-1.
Title: [Extracellular Ca(2+)-sensing receptor-induced extracellular Ca2+ influx is down-regulated by caveolin-1 in human umbilical vein endothelial cells].
These findings support the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction.
Title: Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue.
Data indicate that mutations in the HHD and ECL of the CaSR induce pathway-selective bias that favors the preferential activation (gain of function) or inhibition (loss of function) of one signaling pathway over another.
Title: Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor.
The extracellular calcium-induced increase in cytosolic Ca(2+) due to upregulated CaSR, contributes to the augmented Ca(2+) influx and excessive pulmonary artery smooth muscle cell proliferation in pulmonary arterial hypertension.
Title: Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension.

Submit: New GeneRIF Correction See all (211)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Common genetic variants associate with serum phosphorus concentration.

Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels.

Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P41180	P41180	CASR	HPRD	PubMed
P41180	P21333	FLNA	HPRD	PubMed
P41180	Phosphatidylinositol 4 kinase type II beta	PI4K2B	HPRD	PubMed
P41180	P17252	PRKCA	HPRD	PubMed
P41180	P05771	PRKCB	HPRD	PubMed
P41180	P05129	PRKCG	HPRD	PubMed
P41180	Q9NV58	RNF19A	HPRD	PubMed
BioGRID:107296	BioGRID:107296	CASR	BioGRID	PubMed	Reconstituted Complex
BioGRID:107296	BioGRID:121709	CHD8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107296	BioGRID:108605	FLNA	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:107296	BioGRID:111564	PRKCA	BioGRID	PubMed	Biochemical Activity
BioGRID:107296	BioGRID:111565	PRKCB	BioGRID	PubMed	Biochemical Activity
BioGRID:107296	BioGRID:111568	PRKCG	BioGRID	PubMed	Biochemical Activity
BioGRID:107296	BioGRID:117405	RNF19A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107296	BioGRID:115863	STAMBP	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:107296	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107296	BioGRID:113258	VCP	BioGRID	PubMed	Affinity Capture-Western

Pathways from BioSystems

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Class C/3 (Metabotropic glutamate/pheromone receptors), organism-specific biosystem (from REACTOME)
Class C/3 (Metabotropic glutamate/pheromone receptors), organism-specific biosystemThe class C G-protein-coupled receptors are a class of G-protein coupled receptors that include the metabotropic glutamate receptors and several additional receptors (BrÃ¤uner-Osborne H et al, 2007)....
E-cadherin signaling in keratinocytes, organism-specific biosystem (from Pathway Interaction Database)
E-cadherin signaling in keratinocytes, organism-specific biosystem
E-cadherin signaling in keratinocytes
G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
GPCRs, Class C Metabotropic glutamate, pheromone, organism-specific biosystem (from WikiPathways)
GPCRs, Class C Metabotropic glutamate, pheromone, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.cmbi.kun.nl/7tm/. The groupings are based on the GPCR phylogenetic tree available from the GPCRDB and the training sets used ...
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

General gene information

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Markers

RH103474 (e-PCR)
- UniSTS:97799

SHGC-35350 (e-PCR)
- UniSTS:11541

RH99210 (e-PCR)
- UniSTS:91222

SHGC-77256 (e-PCR)
- UniSTS:7521

D3S3193 (e-PCR)
- UniSTS:153516

SHGC-84714 (e-PCR)
- UniSTS:104110

RH121068 (e-PCR)
- UniSTS:132289

SHGC-147441 (e-PCR)
- UniSTS:175811

Genotypes

See CASR SNP Geneview Report
See CASR SNP Genotype Report
See CASR SNP Variation Viewer Report

Homology

Homologs of the CASR gene: The CASR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G-protein coupled receptor activity	IEA Inferred from Electronic Annotation more info
phosphatidylinositol phospholipase C activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info

Process	Evidence Code	Pubs
G-protein coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
calcium ion import	IDA Inferred from Direct Assay more info
cellular calcium ion homeostasis	TAS Traceable Author Statement more info	PubMed
chemosensory behavior	TAS Traceable Author Statement more info	PubMed
detection of calcium ion	TAS Traceable Author Statement more info	PubMed
ossification	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: extracellular calcium-sensing receptor

Names: extracellular calcium-sensing receptor; parathyroid Ca(2+)-sensing receptor 1; parathyroid cell calcium-sensing receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009058.1 RefSeqGene

Range

5001..107815

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000388.3 → NP_000379.2 extracellular calcium-sensing receptor isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' UTR exon and lacks an in-frame segment in the CDS, as compared to variant 1. The resulting isoform (2) is shorter and lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC068630, AC068754, BP388878, U20759, U20760

Consensus CDS

CCDS3010.1

UniProtKB/Swiss-Prot

P41180

Conserved Domains (4) summary

cd06364
Location:20 – 530
Blast Score: 2610

PBP1_CaSR; Ligand-binding domain of the CaSR calcium-sensing receptor, which is a member of the family C receptors within the G-protein coupled receptor superfamily

pfam07562
Location:538 – 591
Blast Score: 233

NCD3G; Nine Cysteines Domain of family 3 GPCR

pfam00003
Location:622 – 860
Blast Score: 684

7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR

pfam01094
Location:69 – 495
Blast Score: 562

ANF_receptor; Receptor family ligand binding region
NM_001178065.1 → NP_001171536.1 extracellular calcium-sensing receptor isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC068754, BC104999, U20760

Consensus CDS

CCDS54632.1

UniProtKB/Swiss-Prot

P41180

Related

ENSP00000420194, OTTHUMP00000215577, ENST00000498619, OTTHUMT00000355762

Conserved Domains (4) summary

cd06364
Location:20 – 530
Blast Score: 2611

PBP1_CaSR; Ligand-binding domain of the CaSR calcium-sensing receptor, which is a member of the family C receptors within the G-protein coupled receptor superfamily

pfam07562
Location:548 – 601
Blast Score: 233

NCD3G; Nine Cysteines Domain of family 3 GPCR

pfam00003
Location:632 – 870
Blast Score: 682

7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR

pfam01094
Location:69 – 495
Blast Score: 562

ANF_receptor; Receptor family ligand binding region

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p10 Primary Assembly

Range

121902530..122005344

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

119276062..119378878

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018914.1 Alternate CHM1_1.0

Range

121870320..121973134

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01016471.1 (41813..144629)	None
genomic	AC068630.21 (22126..22255)	None
genomic	AC068754.16 (81313..82559)	None
genomic	AMYH01013430.1 (18549..121363)	None
genomic	AY259116.1	AAP20759.1
genomic	CH471052.2	EAW79490.1
		EAW79491.1
		EAW79492.1
genomic	DQ088967.1	AAY68221.1
genomic	DQ327723.1	ABD04091.1
genomic	DQ327724.1	ABD04092.1
genomic	DQ327725.1	ABD04093.1
genomic	DQ327726.1	ABD04094.1
genomic	DQ327727.1	ABD04095.1
genomic	DQ327728.1	ABD04096.1
genomic	GM692549.1	CAV33589.1
genomic	JA910713.1	CCV20013.1
genomic	JB138639.1	CCW28005.1
genomic	S68032.1	AAB29413.2
genomic	S68033.1	AAB29414.1
genomic	S68036.1	AAB29415.1
genomic	X81086.1	CAA56990.1
mRNA	BC104999.1	AAI05000.1
mRNA	BC112236.1	AAI12237.1
mRNA	BP388878.1	None
mRNA	D50855.1	BAA09453.1
mRNA	FJ360896.1	ACJ04039.1
mRNA	S79217.1	AAB35262.2
mRNA	S81755.1	AAD14370.1
mRNA	S83176.1	AAB46873.1
mRNA	U20759.1	AAA86503.1
mRNA	U20760.1	AAA86504.1
mRNA	W56898.1	None