Biomarker: CaSR

Histology type: endometrial carcinoma

Country: China

Region: Wuhan

Followed up time :

Subgroup 1 name : endometrial cance

Subgroup 1 number: 50

Subgroup 2 name: Healthy controls

Subgroup 2 number: 10

Conclusion: Reduced CaSR expression may be a suitable explanation and valuable predictor for endometrial cancer progression.

Sample type : tissue

Sample method: Quantitative PCR/Immunohistochemistry/westernblcok

Expression pattern : positive expression

Expression elevation: The staining intensity was independently evaluated by two pathologists. The scoring categories (none, 0; weak, 1; moderate, 2; and strong, 3) were multiplied by the percentage of positive tumour cells (<10%, 1; 10–49%, 2; >50%, 3) to calculate the final score. A histological score ≤1 point was defined as negative, and ≥2 points was considered as positive.

Funtion description: CaSR is expressed in endometrial cancer where it induces apoptosis. Additionally, activated CaSR facilitates E-cadherin/β-catenin complex formation at the cell membranes of endometrial cancer cells to potentially inhibit tumour invasion.

Funtion Uniprot: 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).

UniProt Link:

Biological function from UniProt: Disease variant, Epilepsy, FDA approved drug targets

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in the temporal lobe, frontal lobe, parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, liver, heart, skeletal muscle, placenta.

Subcellular UniProt: #Cell membrane #Membrane

Activity regulation: In resting state, adopts an open conformation, anion-binding promoting the inactive configuration (PubMed:27434672). Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits (PubMed:27434672, PubMed:27386547). Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor (PubMed:27434672, PubMed:27386547). Activated by AMG 416, a D-amino acid-containing peptide agonist that is being evaluated for the treatment of secondary hyperparathyroidism in chronic kidney disease patients receiving hemodialysis (PubMed:26290606). AMG 416 agonist acts by forming a disulfide bond with Cys-482 (PubMed:26290606).

Gene name from HGNC: CASR (FHH, GPRC2A, HHC, HHC1, NSHPT)

HPA link: https://www.proteinatlas.org/ENSG00000036828-CASR

Tissue specificity RNA from HPA: Tissue enriched (parathyroid gland)

Tissue expression from HPA: Cytoplasmic and membranous expression in islets of Langerhans, parathyroid gland and in a subset of renal tubules.

Subcellular summary HPA Parathyroid cell calcium-sensing receptor 1

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000036828-CASR/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000036828-CASR/pathology/endometrial+cancer

Expression figure legend: Immunocytochemistry for CaSR

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773571/figure/Fig5/

Note2: HHC; FHH FHH1 FAMILIAL BENIGN HYPERCALCEMIA 1; FBH1 HYPERCALCEMIA, FAMILIAL BENIGN;NSPH; NHPT HYPERPARATHYROIDISM, NEONATAL SEVERE PRIMARY;HYPERCALCIURIC HYPOCALCEMIA HYPOCALCEMIA, FAMILIAL;PARATHYROID CA(2+)-SENSING RECEPTOR 1; PCAR1;EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 8; EIG8;

OMIM: 145980; 239200;601198;601199;612899;612899;

OMIM link2: https://www.omim.org/entry/145980;https://www.omim.org/entry/239200;https://www.omim.org/entry/601198;https://www.omim.org/entry/601199;https://www.omim.org/entry/612899;

Phenotype: Hypocalciuric hypercalcemia, type I; Hyperparathyroidism, neonatal;HYPOCALCEMIA, AUTOSOMAL DOMINANT 1; HYPOC1and HYPOCALCEMIA, AUTOSOMAL DOMINANT 1, WITH BARTTER SYNDROME, INCLUDED;CALCIUM-SENSING RECEPTOR; CASR;EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 8; EIG8;

HGNC ID: HGNC:1514

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1514