Calcium-sensing receptor and associated diseases.
The calcium-sensing receptor (CASR) is expressed in parathyroid hormone (PTH)-secreting cells of the parathyroid gland and cells lining the renal tubule. The activated CASR modulates intracellular signaling pathways altering PTH secretion and renal cation and water handling. Inherited abnormalities of the CASR gene give rise to a variety of disorders of mineral ion homeostasis. Heterozygous loss-of-function mutations cause familial (benign) hypocalciuric hypercalcemia (FHH) in which the lifelong mild hypercalcemia is generally asymptomatic. Homozygous inactivating mutations give rise to neonatal severe hyperparathyroidism (NSHPT) with extreme hypercalcemia and marked skeletal changes. Heterozygous activating mutations of the CASR cause autosomal dominant hypocalcemia (ADH) that may be asymptomatic or present with seizures in the neonatal period or childhood or later in life. Phenocopies of FHH or ADH are due to circulating CASR inactivating or activating autoantibodies, respectively. The CASR is the target of small molecule allosteric modifiers, either activators, calcimimetics, or inhibitors, calcilytics.
Hendy
Geoffrey N
GN
Department of Medicine, McGill University, Calcium Research Laboratory, Hormones and Cancer Research Unit, Royal Victoria Hospital, Montreal, Quebec, Canada.
Guarnieri
Vito
V
Canaff
Lucie
L
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004194:Disease; D015536:Down-Regulation; D006706:Homeostasis; D006801:Humans; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D054875:Ubiquitination
D044169:Receptors, Calcium-Sensing; D011493:Protein Kinase C; D002118:Calcium