{"id":"d91e5e54-d92e-513b-8e01-35d05439019f","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:human-trpm6-loss-low-magnesium","predicate":"reduces","statement":"Pathogenic biallelic TRPM6 variants were identified in families with hypomagnesemia and secondary hypocalcemia.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4bbe57a8-9243-5fb8-a106-227ab3895cd7","mechanism_event_label":"Inherited failure of magnesium handling produced a recognizable low-magnesium disorder.","subject":{"id":"e05193a2-4a07-5c8c-bce5-f76ccbc03f09","slug":"trpm6-loss-of-function-genotype","display_name":"TRPM6 loss-of-function genotype","entity_type_key":"gene"},"object":{"id":"623a99ab-787c-5d78-8072-72cfcd82008e","slug":"serum-magnesium-concentration","display_name":"Serum magnesium concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4bbe57a8-9243-5fb8-a106-227ab3895cd7","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:human-trpm6-loss-low-magnesium-event","event_type":"observed_intervention","label":"Inherited failure of magnesium handling produced a recognizable low-magnesium disorder.","description":"Pathogenic biallelic TRPM6 variants were identified in families with hypomagnesemia and secondary hypocalcemia.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"877a2fb0-067c-51ca-afea-f63ff16affc8","slug":"trpm6","display_name":"TRPM6","entity_type_key":"protein"},"role":"affected-protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"depleted-ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"secondarily-affected-ion","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e05193a2-4a07-5c8c-bce5-f76ccbc03f09","slug":"trpm6-loss-of-function-genotype","display_name":"TRPM6 loss-of-function genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"623a99ab-787c-5d78-8072-72cfcd82008e","slug":"serum-magnesium-concentration","display_name":"Serum magnesium concentration","entity_type_key":"cellular_process"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Calcium concentration also fell in the inherited Mg-handling disorder; this record does not specify the downstream endocrine mechanism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence-system","value_text":"Familial positional genetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Familial positional genetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mapping alone does not apportion intestinal versus renal contributions or prove every downstream symptom is Mg-only.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Inherited failure of magnesium handling produced a recognizable low-magnesium disorder.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[schlingmann-2002-trpm6] Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. (2002). https://pubmed.ncbi.nlm.nih.gov/12032568/ DOI: 10.1038/ng889","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Intestine and kidney implicated; serum phenotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestine and kidney implicated; serum phenotype","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":"e907b2f8-70f2-5e5c-bf75-8604a132349c","evidence_kind":"source_excerpt","locator":"Lines 909-921","start_line":909,"end_line":921,"excerpt":"### human-trpm6-loss-low-magnesium\nPathogenic biallelic TRPM6 variants were identified in families with hypomagnesemia and secondary hypocalcemia.\nCondition category: machinery_impairment\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Inherited failure of magnesium handling produced a recognizable low-magnesium disorder.\norganism: Human\ntissue_or_cell_type: Intestine and kidney implicated; serum phenotype\nexperimental_model: Familial positional genetics\nlimitations: Mapping alone does not apportion intestinal versus renal contributions or prove every downstream symptom is Mg-only.\ncross_nutrient: Calcium concentration also fell in the inherited Mg-handling disorder; this record does not specify the downstream endocrine mechanism.\nevidence-system: Familial positional genetics\ntissue: Intestine and kidney implicated; serum phenotype\n[schlingmann-2002-trpm6] Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. (2002). https://pubmed.ncbi.nlm.nih.gov/12032568/ DOI: 10.1038/ng889","model_system":"Familial positional genetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [schlingmann-2002-trpm6] Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. (2002). https://pubmed.ncbi.nlm.nih.gov/12032568/ DOI: 10.1038/ng889","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dd101e28-1a2e-5a48-9d1e-809c77514866","stable_key":"import-0f17db03-207f-5910-ac8e-13dfc2f378ce","title":"Magnesium: cross-nutrient mechanisms and deficiency (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":"e111c412f57143a17e8e65e74e8f7888b5bb9a61099873f4767f527fac19bb07","revision_id":"6b7f04f2-66ed-5859-955f-c2b50d4bf041","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}