{"id":"258e6d45-40a0-521a-928c-a69a4cedc961","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfd1-patient-dna-uracil","predicate":"increases","statement":"MTHFD1-deficient patient fibroblasts contained more uracil in DNA than both control lines.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"19d0b700-b551-5a2f-b9df-2e2e3e813b1e","mechanism_event_label":"The enzyme defect was accompanied by a DNA-base imbalance.","subject":{"id":"a342ad77-da81-58b7-b5b7-288e7424cede","slug":"human-mthfd1-gene","display_name":"Human MTHFD1 gene","entity_type_key":"gene"},"object":{"id":"940ae750-a4e1-506d-bb27-ee6b99b621f1","slug":"nuclear-dna-uracil","display_name":"Uracil incorporation in nuclear DNA","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"19d0b700-b551-5a2f-b9df-2e2e3e813b1e","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfd1-patient-dna-uracil-event","event_type":"biochemical_relationship","label":"The enzyme defect was accompanied by a DNA-base imbalance.","description":"MTHFD1-deficient patient fibroblasts contained more uracil in DNA than both control lines.","status":"provisional","compartment":{"slug":"nucleus","display_name":"Nucleus"},"participants":[{"entity":{"id":"a342ad77-da81-58b7-b5b7-288e7424cede","slug":"human-mthfd1-gene","display_name":"Human MTHFD1 gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"940ae750-a4e1-506d-bb27-ee6b99b621f1","slug":"nuclear-dna-uracil","display_name":"Uracil incorporation in nuclear DNA","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"experimental_model","value_text":"DNA uracil assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Assay conditions described in the linked primary study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Fibroblast endpoint does not itself prove the cause of clinical immunodeficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The enzyme defect was accompanied by a DNA-base imbalance.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[field-2015] Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis (2015). https://pubmed.ncbi.nlm.nih.gov/25548164/ DOI: 10.1073/pnas.1414555112","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"WG3607 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":"ba36f53c-5459-5238-8822-c7ea1b7e080d","evidence_kind":"source_excerpt","locator":"Lines 1182-1192","start_line":1182,"end_line":1192,"excerpt":"### mthfd1-patient-dna-uracil\nMTHFD1-deficient patient fibroblasts contained more uracil in DNA than both control lines.\nCondition category: machinery_impairment\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The enzyme defect was accompanied by a DNA-base imbalance.\norganism: Homo sapiens\ntissue_or_cell_type: WG3607 fibroblasts\nexperimental_model: DNA uracil assay\nlimitations: Fibroblast endpoint does not itself prove the cause of clinical immunodeficiency.\nexposure: Assay conditions described in the linked primary study.\n[field-2015] Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis (2015). https://pubmed.ncbi.nlm.nih.gov/25548164/ DOI: 10.1073/pnas.1414555112","model_system":"DNA uracil assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [field-2015] Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis (2015). https://pubmed.ncbi.nlm.nih.gov/25548164/ DOI: 10.1073/pnas.1414555112","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: 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":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}