Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism.

[familial hypocalciuric hypercalcemia]

The extracellular calcium-sensing receptor (CaSR ) is a family C G-protein-coupled receptor (GPCR ) that is expressed at multiple sites , including the parathyroids and kidneys . The human CASR gene , located on chromosome 3 q 21 .1 , encodes a 1078 amino acid protein . More than 230 different disease-causing mutations of the CaSR have been reported . Loss -of-function mutations lead to three hypercalcemic disorders , which are familial hypocalciuric hypercalcemia (FHH ), neonatal severe hyperparathyroidism and primary hyperparathyroidism . Gain-of-function mutations , on the other hand , result in the hypocalcemic disorders of autosomal dominant hypocalcemia and Bartter syndrome type V . Moreover , autoantibodies directed against the extracellular domain of the CaSR have been found to be associated with FHH in some patients , and also in some patients with hypoparathyroidism that may be part of autoimmune polyglandular syndrome type 1 . Studies of disease-causing CASR mutations have provided insights into structure-function relationships and highlighted intra-molecular domains that are critical for ligand binding , intracellular signaling , and receptor trafficking .

Diseases
Validation

Diseases presenting "loss-of-function mutations" symptom

achondroplasia

alpha-thalassemia

aromatase deficiency

child syndrome

cowden syndrome

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erythropoietic protoporphyria

esophageal adenocarcinoma

familial hypocalciuric hypercalcemia

harlequin ichthyosis

hirschsprung disease

kallmann syndrome

kindler syndrome

lamellar ichthyosis

neonatal adrenoleukodystrophy

pendred syndrome

werner syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated