calcium sensing receptor
Annotations refreshed 1 month ago.
Diagnostic Grade (Green)
Calcium-sensing receptor phenotypes
BOTH monoallelic and biallelic, autosomal or pseudoautosomalFamilial hyperparathyroidism or hypocalciuric hypercalcaemia
BOTH monoallelic and biallelic, autosomal or pseudoautosomalFamilial hypoparathyroidism
BOTH monoallelic and biallelic, autosomal or pseudoautosomalFetal anomalies
BOTH monoallelic and biallelic, autosomal or pseudoautosomalNephrocalcinosis or nephrolithiasis
BOTH monoallelic and biallelic, autosomal or pseudoautosomalOsteogenesis imperfecta
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomalRenal tubulopathies
BOTH monoallelic and biallelic, autosomal or pseudoautosomalSkeletal dysplasia
BOTH monoallelic and biallelic, autosomal or pseudoautosomal+5 more panels — install the extension to see the full list inline on any page.
familial hypocalciuric hypercalcemia 1
autosomal dominant hypocalcemia 1
Familial hypocalciuric hypercalcemia type 1
Familial isolated hypoparathyroidism
neonatal severe primary hyperparathyroidism
familial hypocalciuric hypercalcemia
autosomal dominant hypocalcemia
hyperparathyroidism
Hypercalcemia
parathyroid gland disorder
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Extracellular calcium-sensing receptor
G protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (PubMed:17555508, PubMed:19789209, PubMed:21566075, PubMed:22114145, PubMed:22789683, PubMed:23966241, PubMed:25104082, PubMed:25292184, PubMed:25766501, PubMed:26386835, PubMed:32817431, PubMed:33603117, PubMed:34194040, PubMed:34467854, PubMed:7759551, PubMed:8636323, PubMed:8702647, PubMed:8878438). Senses fluctuations in the circulating calcium concentration: activated by elevated circulating calcium, leading to decreased parathyroid hormone (PTH) secretion in parathyroid glands (By similarity). In kidneys, acts as a key regulator of renal tubular calcium resorption (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:38632411). CASR is coupled with different G(q)/G(11), G(i)/G(o)- or G(s)-classes of G proteins depending on the context (PubMed:38632411). In the parathyroid and kidney, CASR signals through G(q)/G(11) and G(i)/G(o) G proteins: G(q)/G(11) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, while G(i)/G(o) coupling mediates inhibition of adenylate cyclase activity (PubMed:38632411, 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:27386547, PubMed:27434672, PubMed:32817431, PubMed:33603117, PubMed:34194040). Acts as an activator of the NLRP3 inflammasome via G(i)/G(o)-mediated signaling: down-regulation of cyclic AMP (cAMP) relieving NLRP3 inhibition by cAMP (PubMed:32843625). Acts as a regulator of proton-sensing receptor GPR68 in a seesaw manner: CASR-mediated signaling inhibits GPR68 signaling in response to extracellular calcium, while GPR68 inhibits CASR in presence of extracellular protons (By similarity)
Curated MONDO disease pages that list CASR among their top associated genes.
CASR · P41180
Mean pLDDT
75.7/ 100
Confident
1,078 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
