{"id":"d03e3f66-049b-5a0e-9e33-6ede4d99b429","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-e88del-uptake","predicate":"reduces","statement":"Fibroblasts from five asymptomatic newborns with elevated methylmalonic acid and homozygous CD320 p.Glu88del showed reduced uptake of holo-transcobalamin.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"fca1dfb4-85b6-553b-99cb-b7680daf93f1","mechanism_event_label":"A receptor deletion reduced B12 delivery in patient cells.","subject":{"id":"88202cd4-5532-5f43-a30f-7dd11464efb5","slug":"cd320-e88del","display_name":"Human CD320 p.Glu88del variant","entity_type_key":"protein_state"},"object":{"id":"e78d53a1-0ffb-5dc3-8891-83df0f32f6fa","slug":"holo-tc-cellular-uptake","display_name":"Cellular uptake of transcobalamin-bound cobalamin","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fca1dfb4-85b6-553b-99cb-b7680daf93f1","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-e88del-uptake-event","event_type":"biochemical_relationship","label":"A receptor deletion reduced B12 delivery in patient cells.","description":"Fibroblasts from five asymptomatic newborns with elevated methylmalonic acid and homozygous CD320 p.Glu88del showed reduced uptake of holo-transcobalamin.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c0d594d4-1445-57e7-b689-d2fbbb2dc00a","slug":"human-holotranscobalamin","display_name":"Human transcobalamin-cobalamin complex","entity_type_key":"protein_complex"},"role":"cargo","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a2fda496-9308-54c5-b478-bc0b0c175570","slug":"methylmalonic-acid","display_name":"Methylmalonic acid","entity_type_key":"small_molecule"},"role":"associated-marker","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"88202cd4-5532-5f43-a30f-7dd11464efb5","slug":"cd320-e88del","display_name":"Human CD320 p.Glu88del variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"e78d53a1-0ffb-5dc3-8891-83df0f32f6fa","slug":"holo-tc-cellular-uptake","display_name":"Cellular uptake of transcobalamin-bound cobalamin","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"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":"experimental_model","value_text":"Five newborn-derived fibroblast lines with homozygous CD320 deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Homozygous c.262_264delGAG / p.Glu88del","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Asymptomatic neonatal ascertainment does not establish later clinical severity. Cellular uptake does not isolate binding from receptor expression or trafficking.","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":"A receptor deletion reduced B12 delivery in patient cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[quadros-2010-e88del] Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12). (2010). https://pubmed.ncbi.nlm.nih.gov/20524213/ DOI: 10.1002/humu.21297","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human cultured fibroblasts","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":"8614663b-267e-5e00-b997-6c44bdbb0121","evidence_kind":"source_excerpt","locator":"Lines 387-398","start_line":387,"end_line":398,"excerpt":"### b12-abs-e88del-uptake\nFibroblasts from five asymptomatic newborns with elevated methylmalonic acid and homozygous CD320 p.Glu88del showed reduced uptake of holo-transcobalamin.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A receptor deletion reduced B12 delivery in patient cells.\norganism: Homo sapiens\ntissue_or_cell_type: Human cultured fibroblasts\nexperimental_model: Five newborn-derived fibroblast lines with homozygous CD320 deletion\nlimitations: Asymptomatic neonatal ascertainment does not establish later clinical severity. Cellular uptake does not isolate binding from receptor expression or trafficking.\nexposure: Homozygous c.262_264delGAG / p.Glu88del\ncross_nutrient: false\n[quadros-2010-e88del] Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12). (2010). https://pubmed.ncbi.nlm.nih.gov/20524213/ DOI: 10.1002/humu.21297","model_system":"Five newborn-derived fibroblast lines with homozygous CD320 deletion","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [quadros-2010-e88del] Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12). (2010). https://pubmed.ncbi.nlm.nih.gov/20524213/ DOI: 10.1002/humu.21297","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}