{"id":"eb771984-97b7-54a5-ae2a-52ee474597fa","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-mars2-loss","predicate":"supports","statement":"Biallelic MARS2 variants lowered protein abundance; patient cells had complex I/IV defects, and wild-type MARS2 expression increased NDUFB8 and COXII proteins.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b9a7d44b-ac30-5ac0-9ada-aa77b1a7eaf7","mechanism_event_label":"A faulty charging enzyme can impair respiratory machinery despite available methionine.","subject":{"id":"72e741a1-452a-53a7-b8ec-ac441f15ad7d","slug":"mars2","display_name":"Human mitochondrial methionyl-tRNA synthetase / MARS2","entity_type_key":"protein"},"object":{"id":"68276972-fb97-5c88-b038-6a227cb34b17","slug":"human-mars2-respiratory-proteins","display_name":"Respiratory-chain protein abundance in human MARS2-deficient cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b9a7d44b-ac30-5ac0-9ada-aa77b1a7eaf7","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-mars2-loss-event","event_type":"observed_relationship","label":"A faulty charging enzyme can impair respiratory machinery despite available methionine.","description":"Biallelic MARS2 variants lowered protein abundance; patient cells had complex I/IV defects, and wild-type MARS2 expression increased NDUFB8 and COXII proteins.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"72e741a1-452a-53a7-b8ec-ac441f15ad7d","slug":"mars2","display_name":"Human mitochondrial methionyl-tRNA synthetase / MARS2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"68276972-fb97-5c88-b038-6a227cb34b17","slug":"human-mars2-respiratory-proteins","display_name":"Respiratory-chain protein abundance in human MARS2-deficient cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","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; 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unverified.","entity":null}],"evidence":[{"id":"54f4c301-abb8-59b8-8b4d-7d15bf686041","evidence_kind":"source_excerpt","locator":"Lines 100-106","start_line":100,"end_line":106,"excerpt":"## methionine-mars2-loss\nA faulty charging enzyme can impair respiratory machinery despite available methionine.\nBiallelic MARS2 variants lowered protein abundance; patient cells had complex I/IV defects, and wild-type MARS2 expression increased NDUFB8 and COXII proteins.\nModel: Two affected siblings; human fibroblasts/lymphoblasts and gene-expression rescue.\nLimitations: Genetic rescue is not proof that methionine supplementation rescues this disorder.\nEvidence access: Primary abstract\nNovel, compound heterozygous, single-nucleotide variants in MARS2 associated with developmental delay, poor growth, and sensorineural hearing loss. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25754315/ · DOI 10.1002/humu.22781","model_system":"Two affected siblings; human fibroblasts/lymphoblasts and gene-expression rescue.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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