{"id":"10c524a3-5caa-57d1-9f46-969d492911ac","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfs-patient1-enzyme-activity","predicate":"impairment-reduces","statement":"Patient 1 fibroblast lysate had no detectable MTHFS activity in the reported product-formation assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1a5b8ae8-cb0d-5bfd-acc7-c5bf7379d0e6","mechanism_event_label":"These patient cells could not measurably perform the tested folate conversion.","subject":{"id":"f07210ec-3d19-563b-a731-2df6c760f402","slug":"human-mthfs-gene","display_name":"Human MTHFS gene","entity_type_key":"gene"},"object":{"id":"9a1f2454-da04-5158-914f-e3d4d26c61b6","slug":"mthfs","display_name":"Human methenyltetrahydrofolate synthetase / MTHFS","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1a5b8ae8-cb0d-5bfd-acc7-c5bf7379d0e6","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mthfs-patient1-enzyme-activity-event","event_type":"biochemical_relationship","label":"These patient cells could not measurably perform the tested folate conversion.","description":"Patient 1 fibroblast lysate had no detectable MTHFS activity in the reported product-formation assay.","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":"7978c99f-fb17-5d91-a9e4-178558bfa69f","slug":"5-10-methenyltetrahydrofolate","display_name":"5,10-Methenyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"measured product","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""},{"entity":{"id":"9a1f2454-da04-5158-914f-e3d4d26c61b6","slug":"mthfs","display_name":"Human methenyltetrahydrofolate synthetase / MTHFS","entity_type_key":"protein"},"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":"evidence_location","value_text":"Results 3.3 and Figure 4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Fibroblast lysate enzyme assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Lysate enzyme assay versus control; Figure 4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assay-specific nondetection does not prove zero activity in every tissue or separate the two alleles.","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":"These patient cells could not measurably perform the tested folate conversion.","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; unverified.","entity":null}],"evidence":[{"id":"ac8e0bea-ef75-5afa-9153-5725464a47dd","evidence_kind":"source_excerpt","locator":"Lines 1268-1279","start_line":1268,"end_line":1279,"excerpt":"### mthfs-patient1-enzyme-activity\nPatient 1 fibroblast lysate had no detectable MTHFS activity in the reported product-formation assay.\nCondition category: machinery_impairment\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: These patient cells could not measurably perform the tested folate conversion.\norganism: Homo sapiens\ntissue_or_cell_type: Patient 1 skin fibroblasts\nexperimental_model: Fibroblast lysate enzyme assay\nlimitations: Assay-specific nondetection does not prove zero activity in every tissue or separate the two alleles.\nexposure: Lysate enzyme assay versus control; Figure 4.\nevidence_location: Results 3.3 and Figure 4.\n[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","model_system":"Fibroblast lysate enzyme assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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}