{"id":"496319be-2d2f-5a9b-a049-73aa908ad82c","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-marc-a168t-null","predicate":"did_not_reduce","statement":"A168T mice had lower MTARC1 protein despite unchanged mRNA, but neither sex showed significant protection from steatosis, inflammation or fibrosis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"46465af5-e18d-5805-aaaa-2aab962498f1","mechanism_event_label":"Lower protein from this variant was not enough to reproduce knockout protection.","subject":{"id":"f670d2ab-8320-5c9c-b6a5-e54287851a40","slug":"mouse-mtarc1-a168t","display_name":"Mouse Mtarc1 p.Ala168Thr","entity_type_key":"protein_state"},"object":{"id":"688a914a-e1d2-5f5d-8b13-2884642f58f0","slug":"hepatic-triglyceride-accumulation","display_name":"Hepatic triglyceride accumulation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"46465af5-e18d-5805-aaaa-2aab962498f1","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-marc-a168t-null-event","event_type":"biochemical_relationship","label":"Lower protein from this variant was not enough to reproduce knockout protection.","description":"A168T mice had lower MTARC1 protein despite unchanged mRNA, but neither sex showed significant protection from steatosis, inflammation or fibrosis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6a98c6d2-303b-5df3-8ae6-f49e554ed0d3","slug":"mouse-hepatic-mtarc1-protein-abundance","display_name":"Mouse hepatic MTARC1 protein abundance","entity_type_key":"cellular_process"},"role":"decreased measure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3674b224-cb1f-559e-8967-c30efae9e2a7","slug":"hepatic-fibrosis","display_name":"Hepatic fibrosis","entity_type_key":"cellular_process"},"role":"unchanged outcome","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f670d2ab-8320-5c9c-b6a5-e54287851a40","slug":"mouse-mtarc1-a168t","display_name":"Mouse Mtarc1 p.Ala168Thr","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"688a914a-e1d2-5f5d-8b13-2884642f58f0","slug":"hepatic-triglyceride-accumulation","display_name":"Hepatic triglyceride accumulation","entity_type_key":"cellular_process"},"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; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/molybdenum-research/41428769.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5ac3e4efcae2e5b23a255c61586bbff33d3114fe2c8e28befe2d9ad501f774bd\", \"start_char\": 0, \"end_char\": 1816, \"text_sha256\": \"5ac3e4efcae2e5b23a255c61586bbff33d3114fe2c8e28befe2d9ad501f774bd\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Male/female mouse A168T knock-in in multiple MASH/fibrosis models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Mouse ortholog of human A165T; no global knockout","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Partial variant effects are not identical to deleting the gene. No human molybdenum intervention.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Molybdenum research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"molybdenum","display_name":"Molybdenum","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Lower protein from this variant was not enough to reproduce knockout protection.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mo-p41428769] A mitochondrial amidoxime-reducing component 1 (mARC1) A168T amino acid substitution does not confer protection from MASH and fibrosis in multiple mouse models of chronic liver disease. (2026). https://pubmed.ncbi.nlm.nih.gov/41428769/ DOI: 10.1042/bcj20253411","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver disease and protein expression","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":"299d9c36-493b-59b6-9f2b-7562ecad04df","evidence_kind":"source_excerpt","locator":"Lines 1587-1598","start_line":1587,"end_line":1598,"excerpt":"### mo-marc-a168t-null\nA168T mice had lower MTARC1 protein despite unchanged mRNA, but neither sex showed significant protection from steatosis, inflammation or fibrosis.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Lower protein from this variant was not enough to reproduce knockout protection.\norganism: Mus musculus\ntissue_or_cell_type: Liver disease and protein expression\nexperimental_model: Male/female mouse A168T knock-in in multiple MASH/fibrosis models\nlimitations: Partial variant effects are not identical to deleting the gene. No human molybdenum intervention.\nexposure: Mouse ortholog of human A165T; no global knockout\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/41428769.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5ac3e4efcae2e5b23a255c61586bbff33d3114fe2c8e28befe2d9ad501f774bd\", \"start_char\": 0, \"end_char\": 1816, \"text_sha256\": \"5ac3e4efcae2e5b23a255c61586bbff33d3114fe2c8e28befe2d9ad501f774bd\"}\n[mo-p41428769] A mitochondrial amidoxime-reducing component 1 (mARC1) A168T amino acid substitution does not confer protection from MASH and fibrosis in multiple mouse models of chronic liver disease. (2026). https://pubmed.ncbi.nlm.nih.gov/41428769/ DOI: 10.1042/bcj20253411","model_system":"Male/female mouse A168T knock-in in multiple MASH/fibrosis models","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mo-p41428769] A mitochondrial amidoxime-reducing component 1 (mARC1) A168T amino acid substitution does not confer protection from MASH and fibrosis in multiple mouse models of chronic liver disease. 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