{"id":"d23fb2fd-0287-598a-a053-84a24f6ea21c","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abcd4-defect-export","predicate":"pathogenic-variants-impair","statement":"The human disorder assigned to pathogenic ABCD4 mutations showed failure of lysosomal vitamin B12 release, resembling the cblF cellular defect.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f4dd0187-3258-5018-9f7f-afbc71c24b99","mechanism_event_label":"An inherited transporter defect can trap B12 in lysosomes.","subject":{"id":"cbd238bc-ca85-58ef-b68c-cef991742f97","slug":"abcd4-human-gene","display_name":"Human ABCD4 gene","entity_type_key":"gene"},"object":{"id":"4c2a4e50-a50a-5236-9086-0066a8d56af3","slug":"cobalamin-lysosomal-export","display_name":"Cobalamin release from lysosomal lumen to cytosol","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f4dd0187-3258-5018-9f7f-afbc71c24b99","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abcd4-defect-export-event","event_type":"biochemical_relationship","label":"An inherited transporter defect can trap B12 in lysosomes.","description":"The human disorder assigned to pathogenic ABCD4 mutations showed failure of lysosomal vitamin B12 release, resembling the cblF cellular defect.","status":"provisional","compartment":{"slug":"lysosome","display_name":"Lysosome"},"participants":[{"entity":{"id":"831afa98-dacd-516d-ae1e-680432a78525","slug":"abcd4","display_name":"Human ABCD4 lysosomal cobalamin transporter","entity_type_key":"protein"},"role":"encoded transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"trapped nutrient","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"cbd238bc-ca85-58ef-b68c-cef991742f97","slug":"abcd4-human-gene","display_name":"Human ABCD4 gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4c2a4e50-a50a-5236-9086-0066a8d56af3","slug":"cobalamin-lysosomal-export","display_name":"Cobalamin release from lysosomal lumen to cytosol","entity_type_key":"cellular_process"},"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":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cblJ disease and cellular characterization","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Inherited ABCD4 mutations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary abstract supports the release defect; mutation-specific magnitudes were not extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An inherited transporter defect can trap B12 in lysosomes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coelho-2012-abcd4] Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22922874/ DOI: 10.1038/ng.2386","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient-derived cultured 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":"5e27413c-f24b-5823-9a6c-5a8acac1551c","evidence_kind":"source_excerpt","locator":"Lines 557-569","start_line":557,"end_line":569,"excerpt":"### b12-abcd4-defect-export\nThe human disorder assigned to pathogenic ABCD4 mutations showed failure of lysosomal vitamin B12 release, resembling the cblF cellular defect.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An inherited transporter defect can trap B12 in lysosomes.\norganism: Homo sapiens\ntissue_or_cell_type: Patient-derived cultured cells\nexperimental_model: Human cblJ disease and cellular characterization\nlimitations: Primary abstract supports the release defect; mutation-specific magnitudes were not extracted.\nexposure: Inherited ABCD4 mutations\ncross_nutrient: false\nevidence_location: Abstract\n[coelho-2012-abcd4] Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22922874/ DOI: 10.1038/ng.2386","model_system":"Human cblJ disease and cellular characterization","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [coelho-2012-abcd4] Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22922874/ DOI: 10.1038/ng.2386","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}