{"id":"0cf10d82-f2f4-5d2e-b8e1-3d580e4b730b","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-slc25a38-r134c","predicate":"fails-to-restore","statement":"R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"54014c56-708e-5bfc-a46b-b7b478ec21f9","mechanism_event_label":"A disease-associated variant failed the cellular rescue test.","subject":{"id":"a6c7e377-a5ac-5b46-8ece-902510c0429e","slug":"slc25a38-r134c","display_name":"Human SLC25A38 Arg134Cys","entity_type_key":"protein_state"},"object":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"54014c56-708e-5bfc-a46b-b7b478ec21f9","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-slc25a38-r134c-event","event_type":"biochemical_relationship","label":"A disease-associated variant failed the cellular rescue test.","description":"R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"4e146c00-9b97-55d6-ac1c-0a0261378be3","slug":"slc25a38","display_name":"Human SLC25A38","entity_type_key":"protein"},"role":"wild-type rescue comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ef2b6140-11ac-5633-9af3-c2aab23ccc89","slug":"human-slc25a38-knockout","display_name":"Human SLC25A38 knockout genotype","entity_type_key":"gene"},"role":"recipient genotype","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a6c7e377-a5ac-5b46-8ece-902510c0429e","slug":"slc25a38-r134c","display_name":"Human SLC25A38 Arg134Cys","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"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_location","value_text":"Figures 3F and 4C-D","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Variant versus wild-type expression.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No direct PLP transport conclusion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b6","display_name":"Vitamin B6","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A disease-associated variant failed the cellular rescue test.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"K562 cells","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":"7ede2aca-f858-5cb0-95a6-f6e520991e82","evidence_kind":"source_excerpt","locator":"Lines 478-489","start_line":478,"end_line":489,"excerpt":"### b6-transport-slc25a38-r134c\nR134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A disease-associated variant failed the cellular rescue test.\norganism: Homo sapiens\ntissue_or_cell_type: K562 cells\nexperimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.\nlimitations: No direct PLP transport conclusion.\nexposure: Variant versus wild-type expression.\nevidence_location: Figures 3F and 4C-D\n[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3","model_system":"Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"251773bb-16f5-5903-b135-db4a61d9dec4","stable_key":"import-1310afbd-6010-586e-805d-551d846da421","title":"Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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