{"id":"e644a127-5096-5425-bbf7-af3c379178b2","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-tars2-variants","predicate":"when_variant_impairs","statement":"Seven newly reported TARS2 variants were linked to mitochondrial disease, with functional studies demonstrating impaired protein stability or function.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"df6c7a8c-a02c-568f-b481-f3054df2d692","mechanism_event_label":"Enough amino acid cannot by itself guarantee a working loading enzyme.","subject":{"id":"e1304998-8f29-56cc-8535-e65d11c53582","slug":"tars2","display_name":"Human mitochondrial threonyl-tRNA synthetase / TARS2","entity_type_key":"protein"},"object":{"id":"2a46977c-fe06-562f-a829-3326a05f0900","slug":"human-tars2-enzyme-function","display_name":"Human TARS2 stability and catalytic function","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"df6c7a8c-a02c-568f-b481-f3054df2d692","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-tars2-variants-event","event_type":"observed_relationship","label":"Enough amino acid cannot by itself guarantee a working loading enzyme.","description":"Seven newly reported TARS2 variants were linked to mitochondrial disease, with functional studies demonstrating impaired protein stability or function.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e1304998-8f29-56cc-8535-e65d11c53582","slug":"tars2","display_name":"Human mitochondrial threonyl-tRNA synthetase / TARS2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2a46977c-fe06-562f-a829-3326a05f0900","slug":"human-tars2-enzyme-function","display_name":"Human TARS2 stability and catalytic function","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Disease mechanisms differ by variant; response to threonine supplementation was not established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Enough amino acid cannot by itself guarantee a working loading enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257","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":"9c9de788-b159-554f-be96-c93a7ad48fdc","evidence_kind":"source_excerpt","locator":"Lines 82-88","start_line":82,"end_line":88,"excerpt":"## l-threonine-tars2-variants\nEnough amino acid cannot by itself guarantee a working loading enzyme.\nSeven newly reported TARS2 variants were linked to mitochondrial disease, with functional studies demonstrating impaired protein stability or function.\nModel: Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis.\nLimitations: Disease mechanisms differ by variant; response to threonine supplementation was not established.\nEvidence access: Primary abstract\nElucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257","model_system":"Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"35396730-235a-537e-8a05-c6ef2960c509","stable_key":"import-97957230-601f-5dec-8524-0812be8fadbf","title":"L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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