TISIDB

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Multi-pass membrane protein
Domain	PF00003 7 transmembrane sweet-taste receptor of 3 GCPR PF01094 Receptor family ligand binding region PF07562 Nine Cysteines Domain of family 3 GPCR
Function	G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (PubMed:7759551, PubMed:8702647, PubMed:8636323, PubMed:8878438, PubMed:17555508, PubMed:19789209, PubMed:21566075, PubMed:22114145, PubMed:23966241, PubMed:25292184, PubMed:25104082, PubMed:26386835, PubMed:25766501, PubMed:22789683). Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands (By similarity). The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:7759551). The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation (PubMed:27434672, PubMed:27386547).

> Gene Ontology [ TOP ]
Biological Process	GO:0001503 ossification GO:0005513 detection of calcium ion GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0007635 chemosensory behavior GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0044708 single-organism behavior GO:0051592 response to calcium ion GO:0055074 calcium ion homeostasis GO:0070509 calcium ion import GO:0070838 divalent metal ion transport GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport
Molecular Function	GO:0004435 phosphatidylinositol phospholipase C activity GO:0004620 phospholipase activity GO:0004629 phospholipase C activity GO:0008081 phosphoric diester hydrolase activity GO:0016298 lipase activity GO:0042578 phosphoric ester hydrolase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04621 NOD-like receptor signaling pathway
Reactome	R-HSA-420499: Class C/3 (Metabotropic glutamate/pheromone receptors) R-HSA-418594: G alpha (i) signalling events R-HSA-416476: G alpha (q) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CASR and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CASR in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CASR in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.27	0.773
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.22	0.878
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.872	0.564
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.177	0.705
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.04	0.953
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.998	0.0107

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CASR in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	18.5	12.3	6.2	0.518
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	18.5	13.6	4.9	0.535
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	23.8	17.6	6.2	0.709
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	23.1	27.3	-4.2	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	15.8	3.7	12.1	0.224
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	7.7	5.9	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	18.8	0	18.8	0.228
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CASR. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CASR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CASR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CASR. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CASR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CASR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CASR
Name	calcium-sensing receptor
Aliases	FHH; NSHPT; GPRC2A; severe neonatal hyperparathyroidism; HHC; HHC1; hypocalciuric hypercalcemia 1; EIG8; FIH ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CASR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CASR.

ID	Name	Drug Type	Targets	#Targets
DB00127	Spermine	Small Molecule	ADRB1, ADRB2, CASR, ODC1, SMOX, SMS	6
DB00994	Neomycin	Small Molecule	CASR	1
DB01012	Cinacalcet	Small Molecule	CASR	1
DB05255	Ronacaleret	Small Molecule	ADGRF1, CASR	2
DB05695	NPS-2143	Small Molecule	CASR	1
DB11093	Calcium Citrate	Small Molecule	CADPS, CADPS2, CALB2, CALR, CALR3, CANX, CAPS, CASQ1, CASQ2, CASR, ......	29
DB11348	Calcium Phosphate	Small Molecule	CADPS, CADPS2, CALB2, CALR, CALR3, CANX, CAPS, CASQ1, CASQ2, CASR, ......	29
DB12865	Etelcalcetide	Small Molecule	CASR	1

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