{"id":"64f8e428-a8cd-50de-9d65-fb7b6cced0b8","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-hars2-splicing","predicate":"reduces_tested","statement":"The nucleotide change encoding HARS2 L200V also generated a transcript lacking 12 codons; the deletion product was not stably expressed in mammalian mitochondria.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1e6cd403-8e70-555f-ae3a-f153199938b6","mechanism_event_label":"One DNA change affected both the protein sequence and how its RNA was assembled.","subject":{"id":"200b705b-da4c-5c09-ba16-e386a0877376","slug":"human-hars2-l200v-splice","display_name":"Human HARS2 L200V-associated altered splicing","entity_type_key":"cellular_process"},"object":{"id":"8f0018e1-087e-570e-ab8b-d1bc980d2a74","slug":"hars2","display_name":"Human mitochondrial histidyl-tRNA synthetase / HARS2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1e6cd403-8e70-555f-ae3a-f153199938b6","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-hars2-splicing-event","event_type":"observed_relationship","label":"One DNA change affected both the protein sequence and how its RNA was assembled.","description":"The nucleotide change encoding HARS2 L200V also generated a transcript lacking 12 codons; the deletion product was not stably expressed in mammalian mitochondria.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"200b705b-da4c-5c09-ba16-e386a0877376","slug":"human-hars2-l200v-splice","display_name":"Human HARS2 L200V-associated altered splicing","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8f0018e1-087e-570e-ab8b-d1bc980d2a74","slug":"hars2","display_name":"Human mitochondrial histidyl-tRNA synthetase / HARS2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","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":"Perrault-syndrome family, transcript analysis and expression assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A machinery defect is not evidence of dietary histidine deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"One DNA change affected both the protein sequence and how its RNA was assembled.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21464306/ · DOI 10.1073/pnas.1103471108","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":"b9921612-6b0f-5dae-ae42-d9f94bb41092","evidence_kind":"source_excerpt","locator":"Lines 482-488","start_line":482,"end_line":488,"excerpt":"## histidine-hars2-splicing\nOne DNA change affected both the protein sequence and how its RNA was assembled.\nThe nucleotide change encoding HARS2 L200V also generated a transcript lacking 12 codons; the deletion product was not stably expressed in mammalian mitochondria.\nModel: Perrault-syndrome family, transcript analysis and expression assays.\nLimitations: A machinery defect is not evidence of dietary histidine deficiency.\nEvidence access: Primary abstract\nMutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21464306/ · DOI 10.1073/pnas.1103471108","model_system":"Perrault-syndrome family, transcript analysis and expression assays.","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":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors 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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