{"id":"f1b3ddcd-7b85-5838-8b08-aa02f8ac4147","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-prdx1-readthrough","predicate":"splice-variants-produce","statement":"PRDX1 splice-acceptor variants c.515-1G>T or c.515-2A>T were linked to exon-6/termination-signal skipping and antisense readthrough across MMACHC in epi-cblC fibroblasts.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"27d72e00-c8f6-5ff2-aa47-c401a0600f6a","mechanism_event_label":"A neighboring gene’s splice defect made transcription run through the B12-processing gene.","subject":{"id":"7e130403-e1f2-57cd-8673-a7f1710ce4a4","slug":"prdx1-human-gene","display_name":"Human PRDX1 gene","entity_type_key":"gene"},"object":{"id":"4f03117c-efe5-5b6a-abfa-cb40c1db70c2","slug":"prdx1-readthrough-rna","display_name":"PRDX1 readthrough antisense RNA across MMACHC","entity_type_key":"rna"},"evidence_count":1,"mechanism_event":{"id":"27d72e00-c8f6-5ff2-aa47-c401a0600f6a","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-prdx1-readthrough-event","event_type":"biochemical_relationship","label":"A neighboring gene’s splice defect made transcription run through the B12-processing gene.","description":"PRDX1 splice-acceptor variants c.515-1G>T or c.515-2A>T were linked to exon-6/termination-signal skipping and antisense readthrough across MMACHC in epi-cblC fibroblasts.","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":"overlapped 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":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4f03117c-efe5-5b6a-abfa-cb40c1db70c2","slug":"prdx1-readthrough-rna","display_name":"PRDX1 readthrough antisense RNA across MMACHC","entity_type_key":"rna"},"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":"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":"Human epi-cblC fibroblast RNA-seq and RT-PCR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Inherited PRDX1 splice variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Specific cis-acting alleles; does not imply ordinary PRDX1 antioxidant activity suppresses B12 processing.","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 neighboring gene’s splice defect made transcription run through the B12-processing gene.","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":"Patient skin 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":"fb609310-c9df-5e57-a047-7e45029ea6f0","evidence_kind":"source_excerpt","locator":"Lines 907-919","start_line":907,"end_line":919,"excerpt":"### b12-prdx1-readthrough\nPRDX1 splice-acceptor variants c.515-1G>T or c.515-2A>T were linked to exon-6/termination-signal skipping and antisense readthrough across MMACHC in epi-cblC fibroblasts.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A neighboring gene’s splice defect made transcription run through the B12-processing gene.\norganism: Homo sapiens\ntissue_or_cell_type: Patient skin fibroblasts\nexperimental_model: Human epi-cblC fibroblast RNA-seq and RT-PCR\nlimitations: Specific cis-acting alleles; does not imply ordinary PRDX1 antioxidant activity suppresses B12 processing.\nexposure: Inherited PRDX1 splice variants\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":"Human epi-cblC fibroblast RNA-seq and RT-PCR","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}