{"id":"d9971111-5909-5e40-95ed-551926dc427f","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-pnpo-splice","predicate":"abolishes-measured-activity-of","statement":"The human PNPO IVS3-1G>A splice-site construct had no detectable PNPO activity in the reported CHO expression assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f2b3215d-e07e-5293-98d5-9433a30168ea","mechanism_event_label":"This variant prevented measured B6 activation.","subject":{"id":"1d0b3c61-3c15-555e-80e9-2d5913ca37be","slug":"human-pnpo-ivs3-1g-a","display_name":"Human PNPO IVS3-1G>A splice genotype","entity_type_key":"gene"},"object":{"id":"a01d08b9-a749-5bc3-934b-af0b35024b54","slug":"pnpo","display_name":"Pyridoxine 5-prime-phosphate oxidase / PNPO","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f2b3215d-e07e-5293-98d5-9433a30168ea","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-pnpo-splice-event","event_type":"biochemical_relationship","label":"This variant prevented measured B6 activation.","description":"The human PNPO IVS3-1G>A splice-site construct had no detectable PNPO activity in the reported CHO expression assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"activation product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1d0b3c61-3c15-555e-80e9-2d5913ca37be","slug":"human-pnpo-ivs3-1g-a","display_name":"Human PNPO IVS3-1G>A splice genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a01d08b9-a749-5bc3-934b-af0b35024b54","slug":"pnpo","display_name":"Pyridoxine 5-prime-phosphate oxidase / PNPO","entity_type_key":"protein"},"role":"target","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_location","value_text":"Indexed abstract: CHO expression studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Five affected patients and human PNPO constructs expressed in CHO cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Construct expression, not nutrient withdrawal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cannot generalize to every PNPO variant or vitamer treatment response.","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 protein expressed in Cricetulus griseus cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This variant prevented measured B6 activation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CHO expression system","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":"17cf8a71-cfd4-509c-a77e-d6cfdbf16c2c","evidence_kind":"source_excerpt","locator":"Lines 361-372","start_line":361,"end_line":372,"excerpt":"### b6-transport-pnpo-splice\nThe human PNPO IVS3-1G>A splice-site construct had no detectable PNPO activity in the reported CHO expression assay.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This variant prevented measured B6 activation.\norganism: Homo sapiens protein expressed in Cricetulus griseus cells\ntissue_or_cell_type: CHO expression system\nexperimental_model: Five affected patients and human PNPO constructs expressed in CHO cells.\nlimitations: Cannot generalize to every PNPO variant or vitamer treatment response.\nexposure: Construct expression, not nutrient withdrawal.\nevidence_location: Indexed abstract: CHO expression studies\n[mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120","model_system":"Five affected patients and human PNPO constructs expressed in CHO cells.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mills2005] Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (2005). https://pubmed.ncbi.nlm.nih.gov/15772097/ DOI: 10.1093/hmg/ddi120","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. Not publisher full text.","file_path":"","sha256":"ef0019b344b2219220f801a84d0d138ff6880c1be1a59540d9034bfa4334f61e","revision_id":"cac3555f-48af-5c52-a84e-add4482c87fb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}