{"id":"805bfec3-cb60-5074-8eb6-aa1b9f6dd1ca","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-etfdh-responsive-milder-folding","predicate":"shows-context-dependent-folding","statement":"Under the same supplemented culture conditions, ETF-QO variants linked to riboflavin-responsive MADD exhibited milder folding defects than the nonresponsive or partly responsive variants.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"38214239-6bd3-5bf7-8fba-69f02181f830","mechanism_event_label":"Different inherited changes left different amounts of rescuable protein function.","subject":{"id":"c58bbfd3-2d2a-56a8-be86-ce22d1790cb2","slug":"etfdh-2012-variant-panel","display_name":"Human ETF-QO variants studied by Cornelius 2012","entity_type_key":"protein_set"},"object":{"id":"9f78394a-ddd1-5874-a9f7-e848262b5761","slug":"etfdh","display_name":"Human electron transfer flavoprotein dehydrogenase / ETFDH","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"38214239-6bd3-5bf7-8fba-69f02181f830","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-etfdh-responsive-milder-folding-event","event_type":"biochemical_relationship","label":"Different inherited changes left different amounts of rescuable protein function.","description":"Under the same supplemented culture conditions, ETF-QO variants linked to riboflavin-responsive MADD exhibited milder folding defects than the nonresponsive or partly responsive variants.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"role":"culture exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"derived cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c58bbfd3-2d2a-56a8-be86-ce22d1790cb2","slug":"etfdh-2012-variant-panel","display_name":"Human ETF-QO variants studied by Cornelius 2012","entity_type_key":"protein_set"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9f78394a-ddd1-5874-a9f7-e848262b5761","slug":"etfdh","display_name":"Human electron transfer flavoprotein dehydrogenase / ETFDH","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Different inherited changes left different amounts of rescuable protein function.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK-293 expression system","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":"0ff334e7-324b-535f-a8b8-ab7ff5c7ec34","evidence_kind":"source_excerpt","locator":"Lines 821-832","start_line":821,"end_line":832,"excerpt":"### b2-met-etfdh-responsive-milder-folding\nUnder the same supplemented culture conditions, ETF-QO variants linked to riboflavin-responsive MADD exhibited milder folding defects than the nonresponsive or partly responsive variants.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Different inherited changes left different amounts of rescuable protein function.\norganism: Homo sapiens\ntissue_or_cell_type: HEK-293 expression system\nexperimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.\nlimitations: Response-associated molecular comparison; no dose recommendation and no claim that all missense variants respond.\nexposure: Variant expression with supplemented riboflavin, comparing clinical response groups.\nevidence_spans: [{\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMID22611163\", \"locator\": \"metadata.abstractText\", \"paragraph_index\": 0, \"char_start\": 0, \"char_end\": 1899, \"evidence_access\": \"primary-abstract\"}]\n[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175","model_system":"Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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