{"id":"e5e5d928-ba5a-5c31-98a5-bccb2074c445","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:trpm6-s141l-assembly-defect","predicate":"disrupts","statement":"TRPM6 S141L disrupted oligomeric assembly and functional TRPM6/TRPM7 complex formation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"521ae0df-19e0-55d5-aa99-713fc210799f","mechanism_event_label":"This disease-associated substitution damages assembly of the magnesium-entry machinery.","subject":{"id":"a44218b6-036a-579d-abb0-52eeaa571839","slug":"trpm6-s141l","display_name":"TRPM6 S141L","entity_type_key":"protein_state"},"object":{"id":"80ac07f5-bdf8-5714-8b8c-c687f59bb519","slug":"trpm6-trpm7-complex","display_name":"TRPM6/TRPM7 heteromeric channel complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"521ae0df-19e0-55d5-aa99-713fc210799f","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:trpm6-s141l-assembly-defect-event","event_type":"biochemical_relationship","label":"This disease-associated substitution damages assembly of the magnesium-entry machinery.","description":"TRPM6 S141L disrupted oligomeric assembly and functional TRPM6/TRPM7 complex formation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"877a2fb0-067c-51ca-afea-f63ff16affc8","slug":"trpm6","display_name":"TRPM6","entity_type_key":"protein"},"role":"wild-type-reference","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"16ade5d1-e269-5904-9ab1-b285509b7aef","slug":"trpm7","display_name":"TRPM7","entity_type_key":"protein"},"role":"channel-partner","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a44218b6-036a-579d-abb0-52eeaa571839","slug":"trpm6-s141l","display_name":"TRPM6 S141L","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"80ac07f5-bdf8-5714-8b8c-c687f59bb519","slug":"trpm6-trpm7-complex","display_name":"TRPM6/TRPM7 heteromeric channel complex","entity_type_key":"protein_complex"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence-system","value_text":"Mutant coexpression and channel assembly assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mutant coexpression and channel assembly assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A particular variant mechanism; not all TRPM6 variants act by defective trafficking.","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 proteins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This disease-associated substitution damages assembly of the magnesium-entry machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"HEK293 and Xenopus expression systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293 and Xenopus expression systems","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":"3b6ed47d-e54b-59d1-b141-02168e6a435a","evidence_kind":"source_excerpt","locator":"Lines 896-907","start_line":896,"end_line":907,"excerpt":"### trpm6-s141l-assembly-defect\nTRPM6 S141L disrupted oligomeric assembly and functional TRPM6/TRPM7 complex formation.\nCondition category: machinery_impairment\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This disease-associated substitution damages assembly of the magnesium-entry machinery.\norganism: Human proteins\ntissue_or_cell_type: HEK293 and Xenopus expression systems\nexperimental_model: Mutant coexpression and channel assembly assays\nlimitations: A particular variant mechanism; not all TRPM6 variants act by defective trafficking.\nevidence-system: Mutant coexpression and channel assembly assays\ntissue: HEK293 and Xenopus expression systems\n[chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101","model_system":"Mutant coexpression and channel assembly assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101","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. 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