{"id":"9ca2dc9e-b304-5211-a40c-46ff325548ee","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-mmachc-epi-silencing","predicate":"silences","statement":"In CHU-12122 epi-cblC fibroblasts, the promoter-hypermethylated paternal MMACHC allele was transcriptionally silent; only the maternal coding-mutant allele was detected in transcripts.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"47c04e64-6477-511e-951e-2b70b4d19c2d","mechanism_event_label":"The intact B12-processing allele was switched off by the inherited epigenetic defect.","subject":{"id":"7dedb078-68f1-5d05-8adc-3740da95d370","slug":"mmachc-promoter-methylation","display_name":"MMACHC promoter CpG methylation","entity_type_key":"cellular_process"},"object":{"id":"700c8b0a-3f2d-5094-8255-693726624f40","slug":"mmachc-gene-expression","display_name":"MMACHC gene transcription","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"47c04e64-6477-511e-951e-2b70b4d19c2d","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-mmachc-epi-silencing-event","event_type":"biochemical_relationship","label":"The intact B12-processing allele was switched off by the inherited epigenetic defect.","description":"In CHU-12122 epi-cblC fibroblasts, the promoter-hypermethylated paternal MMACHC allele was transcriptionally silent; only the maternal coding-mutant allele was detected in transcripts.","status":"provisional","compartment":{"slug":"nucleus","display_name":"Nucleus"},"participants":[{"entity":{"id":"72124e1e-7779-5875-92b9-85aee38ecf94","slug":"mmachc-human-gene","display_name":"Human MMACHC gene","entity_type_key":"gene"},"role":"affected locus","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7e130403-e1f2-57cd-8673-a7f1710ce4a4","slug":"prdx1-human-gene","display_name":"Human PRDX1 gene","entity_type_key":"gene"},"role":"cis-associated variant","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7dedb078-68f1-5d05-8adc-3740da95d370","slug":"mmachc-promoter-methylation","display_name":"MMACHC promoter CpG methylation","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"700c8b0a-3f2d-5094-8255-693726624f40","slug":"mmachc-gene-expression","display_name":"MMACHC gene transcription","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":"Results: Figures 1, 4–6; Methods: PRDX1 silencing","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Allele-specific human epi-cblC expression and bisulfite analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Paternal secondary epimutation plus maternal c.270_271insA coding variant","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Family-specific compound genetic/epigenetic machinery defect; not a nutritional methylation intervention.","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":"The intact B12-processing allele was switched off by the inherited epigenetic defect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CHU-12122 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":"a6ca9691-6681-551e-be9c-59b5aecc86dc","evidence_kind":"source_excerpt","locator":"Lines 921-933","start_line":921,"end_line":933,"excerpt":"### b12-mmachc-epi-silencing\nIn CHU-12122 epi-cblC fibroblasts, the promoter-hypermethylated paternal MMACHC allele was transcriptionally silent; only the maternal coding-mutant allele was detected in transcripts.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The intact B12-processing allele was switched off by the inherited epigenetic defect.\norganism: Homo sapiens\ntissue_or_cell_type: CHU-12122 fibroblasts\nexperimental_model: Allele-specific human epi-cblC expression and bisulfite analysis\nlimitations: Family-specific compound genetic/epigenetic machinery defect; not a nutritional methylation intervention.\nexposure: Paternal secondary epimutation plus maternal c.270_271insA coding variant\ncross_nutrient: false\nevidence_location: Results: Figures 1, 4–6; Methods: PRDX1 silencing\n[gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5","model_system":"Allele-specific human epi-cblC expression and bisulfite analysis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5","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}