{"id":"85317630-671c-553a-8e97-8d08318026bc","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-trpm6-variants-insulin-response","predicate":"loses_stimulation_by","statement":"Insulin failed to activate tested TRPM6 V1393I and K1584E variants.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"73fa4867-72b2-5245-b960-4f316fd27b0e","mechanism_event_label":"A change in the channel can interrupt the signal even when insulin is present.","subject":{"id":"720f6460-8c2a-5989-8320-21932d0e7432","slug":"trpm6-v1393i","display_name":"TRPM6 V1393I variant","entity_type_key":"protein_state"},"object":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"73fa4867-72b2-5245-b960-4f316fd27b0e","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-trpm6-variants-insulin-response-event","event_type":"biochemical_relationship","label":"A change in the channel can interrupt the signal even when insulin is present.","description":"Insulin failed to activate tested TRPM6 V1393I and K1584E variants.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fd033496-40bc-5c39-b8db-a9dc1ee6157b","slug":"trpm6-k1584e","display_name":"TRPM6 K1584E variant","entity_type_key":"protein_state"},"role":"second_tested_variant","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"877a2fb0-067c-51ca-afea-f63ff16affc8","slug":"trpm6","display_name":"TRPM6","entity_type_key":"protein"},"role":"wild_type_comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"transport_context","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"720f6460-8c2a-5989-8320-21932d0e7432","slug":"trpm6-v1393i","display_name":"TRPM6 V1393I variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"role":"target","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":"Insulin/TRPM6/Mg interaction can depend on genotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mutant-versus-wild-type channel assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Nearby phosphorylation-site effects are proposed; association with pregnancy glycemia does not prove nutritional causality.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A change in the channel can interrupt the signal even when insulin is present.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"TRPM6-expressing cells; plasma membrane","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":"e0f0a24d-eba0-5a92-aa62-4aa6bb85150b","evidence_kind":"source_excerpt","locator":"Lines 1539-1549","start_line":1539,"end_line":1549,"excerpt":"### mg-trpm6-variants-insulin-response\nInsulin failed to activate tested TRPM6 V1393I and K1584E variants.\nCondition category: machinery_impairment\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A change in the channel can interrupt the signal even when insulin is present.\norganism: Homo sapiens\ntissue_or_cell_type: TRPM6-expressing cells; plasma membrane\nexperimental_model: Mutant-versus-wild-type channel assays.\nlimitations: Nearby phosphorylation-site effects are proposed; association with pregnancy glycemia does not prove nutritional causality.\ncross_nutrient: Insulin/TRPM6/Mg interaction can depend on genotype.\n[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109","model_system":"Mutant-versus-wild-type channel assays.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109","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}