{"id":"8d7bd0cb-d26e-5d35-b748-ee0a6a7cf74a","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfs-patient1-folinic-accumulation","predicate":"impairment-increases","statement":"Patient 1 fibroblasts accumulated about 30-fold more 5-formyl-THF than control cells.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e43b44f5-049c-5400-b3cb-4ac5478411da","mechanism_event_label":"The substrate built up in cells with impaired MTHFS.","subject":{"id":"f07210ec-3d19-563b-a731-2df6c760f402","slug":"human-mthfs-gene","display_name":"Human MTHFS gene","entity_type_key":"gene"},"object":{"id":"bab4af27-0401-545c-aa8f-e945920e614b","slug":"5-formyltetrahydrofolate","display_name":"5-Formyltetrahydrofolate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"e43b44f5-049c-5400-b3cb-4ac5478411da","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfs-patient1-folinic-accumulation-event","event_type":"observed_intervention","label":"The substrate built up in cells with impaired MTHFS.","description":"Patient 1 fibroblasts accumulated about 30-fold more 5-formyl-THF than control cells.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"4e67198f-4d8e-5f02-b31f-2f25b4a85bbd","slug":"mthfs-r145q","display_name":"Human MTHFS p.Arg145Gln","entity_type_key":"protein_state"},"role":"variant allele","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cc903809-f3f9-579d-bc2d-921a31f06708","slug":"mthfs-l36p","display_name":"Human MTHFS p.Leu36Pro","entity_type_key":"protein_state"},"role":"variant allele","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f07210ec-3d19-563b-a731-2df6c760f402","slug":"human-mthfs-gene","display_name":"Human MTHFS gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bab4af27-0401-545c-aa8f-e945920e614b","slug":"5-formyltetrahydrofolate","display_name":"5-Formyltetrahydrofolate","entity_type_key":"small_molecule"},"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":"evidence_location","value_text":"Results 3.4 and Figure 5.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cellular folate mass spectrometry","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Patient 1183-01 versus EC/BJ control fibroblasts; Figure 5.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Substrate accumulation does not establish that it causes the neurologic phenotype.","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 substrate built up in cells with impaired MTHFS.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[rodan-2018] 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination (2018). https://pubmed.ncbi.nlm.nih.gov/30031689/ DOI: 10.1016/j.ymgme.2018.06.006","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient 1 skin fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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Study references: [rodan-2018] 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination (2018). https://pubmed.ncbi.nlm.nih.gov/30031689/ DOI: 10.1016/j.ymgme.2018.06.006","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}