Calcium-Sensing Receptor Positive Allosteric Modulation Module

Two deliberate omissions, both about terms that do not exist rather than steps that are unclear. GO has no calcium-sensing receptor activity term: searching OLS go for 'calcium-sensing receptor activity' returns two calcium channel activities (GO:0005220 and GO:0005219) and nothing for the receptor, and 'extracellular calcium ion sensing' returns nothing at all, so the trigger sits on the generic GO:0004930 G protein-coupled receptor activity and the receptor identity is carried by the CASR gene binding (hgnc:1514) instead. And no transducer is bound. The calcium-sensing receptor does couple through Gq/11 and phospholipase C, but none of the abstracts cited here states that step, and binding GO terms for a chain no cited source names is the defect this module was written to avoid; the sensitisation node therefore carries no process term and says what the sources do say, which is that the drug raises the receptor's sensitivity to extracellular calcium. Whoever sources the coupling can add it. The module is grounded on two drugs, not one. Cinacalcet is the small molecule and etelcalcetide the intravenous peptide; PMID:29534286 is cited for the sensitisation step precisely because it states the mechanism for etelcalcetide and names the chief cell, so the module is not a cinacalcet module. Hypocalcaemia is modelled as a consequence arm rather than as an adverse-effect aside, because it is the same mechanism read at the organism scale: suppressing parathyroid hormone lowers serum calcium, and in the cited haemodialysis cohort two thirds of patients initiating cinacalcet became hypocalcaemic. That source also reports it was mostly asymptomatic and transient, which is quoted on the node so the arm is not read as a stronger safety claim than the source makes. The treatment block sets therapeutic_modality to SMALL_MOLECULE, which describes cinacalcet; the slot is single-valued and etelcalcetide is a peptide, so that value names the oral drug rather than the whole class. Parathyroid cell proliferation is not modelled. Calcimimetics are reported to affect parathyroid hyperplasia as well as secretion, but no abstract cited here establishes it, so there is no node for it. Five conformers are wired: CKD-Mineral_Bone_Disorder, Familial_Hypocalciuric_Hypercalcemia_1 and _2, Parathyroid_Gland_Carcinoma and Parathyroid_Hyperplasia. They span reduced renal handling, an inactivating receptor or G-protein variant, autonomous malignant tissue and autonomous hyperplastic tissue, which is what makes the module indication-independent. Two further entries name a calcimimetic and are deliberately not wired. Multiple_Endocrine_Neoplasia_Type_1 has no calcimimetic treatment to wire: the drug is named only inside a parathyroidectomy treatment, which binds no agent of its own. Autosomal_Recessive_Hypophosphatemic_Rickets_1 records a single adjunctive course in one adult that was stopped because higher doses were not tolerated, and the entry says explicitly that it does not establish routine efficacy; wiring it would present an abandoned single-patient trial as a therapeutic mechanism of that disease. The autosomal dominant hypocalcaemia entries are NOT conformers and must not be wired here: they are caused by activating receptor variants, so a calcimimetic is the wrong direction of action and those entries mention it as a thing to avoid. A calcilytic module, if one is ever written, is where they would belong.