{"id":"a11bc99e-a0a2-5778-ae75-26c823530be1","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:casr-loss-hypercalcemia","predicate":"loss_of_function_associated_with_increase","statement":"Inactivating CASR variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"b5a91511-1727-5f78-b110-a61a362b137d","mechanism_event_label":"A faulty sensor can raise blood calcium.","subject":{"id":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"object":{"id":"068b1eb6-c8bf-59d3-98a0-df623ad01b52","slug":"serum-calcium-concentration","display_name":"Serum calcium concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b5a91511-1727-5f78-b110-a61a362b137d","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:casr-loss-hypercalcemia-event","event_type":"biochemical_relationship","label":"A faulty sensor can raise blood calcium.","description":"Inactivating CASR variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"role":"impaired_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"regulated_ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"068b1eb6-c8bf-59d3-98a0-df623ad01b52","slug":"serum-calcium-concentration","display_name":"Serum calcium concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"experimental_model","value_text":"Human pedigrees and mutant-receptor expression in Xenopus oocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mutation-specific inherited disease; not evidence of dietary calcium excess.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A faulty sensor can raise blood calcium.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[pollak1993] Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism (1993). https://pubmed.ncbi.nlm.nih.gov/7916660/ DOI: 10.1016/0092-8674(93)90617-y","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Parathyroid/kidney calcium regulation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"acb4dc6d-10a3-5cc7-bfa8-0dd6b1ce139b","evidence_kind":"source_excerpt","locator":"Lines 36-45","start_line":36,"end_line":45,"excerpt":"### casr-loss-hypercalcemia\nInactivating CASR variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A faulty sensor can raise blood calcium.\norganism: Homo sapiens\ntissue_or_cell_type: Parathyroid/kidney calcium regulation\nexperimental_model: Human pedigrees and mutant-receptor expression in Xenopus oocytes\nlimitations: Mutation-specific inherited disease; not evidence of dietary calcium excess.\n[pollak1993] Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism (1993). https://pubmed.ncbi.nlm.nih.gov/7916660/ DOI: 10.1016/0092-8674(93)90617-y","model_system":"Human pedigrees and mutant-receptor expression in Xenopus oocytes","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [pollak1993] Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism (1993). https://pubmed.ncbi.nlm.nih.gov/7916660/ DOI: 10.1016/0092-8674(93)90617-y","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"06ed5146-dc3c-5e95-82cc-e778c2e64300","title":"CaSR variant direction changes the calcium phenotype","kind":"context_difference","status":"open","why":"Reduced receptor activity and increased receptor activity cause opposite blood-calcium disturbances.","resolution":"Curation interpretation: Specify gain versus loss of function; neither phenotype establishes dietary calcium intake.","created_at":"2026-09-17 08:08:54","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/06ed5146-dc3c-5e95-82cc-e778c2e64300","sides":[{"conflict_id":"06ed5146-dc3c-5e95-82cc-e778c2e64300","ordinal":0,"label":"A faulty sensor can raise blood calcium.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":36,"end_line":45,"quote":"### casr-loss-hypercalcemia\nInactivating CASR variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A faulty sensor can raise blood calcium.\norganism: Homo sapiens\ntissue_or_cell_type: Parathyroid/kidney calcium regulation\nexperimental_model: Human pedigrees and mutant-receptor expression in Xenopus oocytes\nlimitations: Mutation-specific inherited disease; not evidence of dietary calcium excess.\n[pollak1993] Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism (1993). https://pubmed.ncbi.nlm.nih.gov/7916660/ DOI: 10.1016/0092-8674(93)90617-y","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["a11bc99e-a0a2-5778-ae75-26c823530be1"]},{"conflict_id":"06ed5146-dc3c-5e95-82cc-e778c2e64300","ordinal":1,"label":"An oversensitive sensor can lower blood calcium.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":47,"end_line":56,"quote":"### casr-gain-hypocalcemia\nThe CaSR E128A variant increases receptor responsiveness and causes dominant hypocalcemia in the studied family.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An oversensitive sensor can lower blood calcium.\norganism: Homo sapiens\ntissue_or_cell_type: Systemic calcium regulation\nexperimental_model: Human family; E128A CaSR expressed in Xenopus oocytes\nlimitations: One family and oocyte assays; not dietary calcium deficiency.\n[pollak1994] Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation (1994). https://pubmed.ncbi.nlm.nih.gov/7874174/ DOI: 10.1038/ng1194-303","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["7765f71d-b36e-543e-99c9-592362fc04eb"]}]}],"corrections":[],"research":null}