{"id":"d3e46120-b2fd-552c-a9c8-a8bf146bec7a","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-mat1-loss","predicate":"limits_accumulation_when_functional","statement":"Reduced MAT I/III function caused persistent hypermethioninemia in patients with biallelic MAT1A variants.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0f5933f9-e13f-5095-8cc4-817174037f62","mechanism_event_label":"High substrate can signal failure to process it.","subject":{"id":"7fdec12b-82f3-5c55-88fb-32428555c7c6","slug":"mat1a","display_name":"Human methionine adenosyltransferase 1A / MAT1A","entity_type_key":"protein"},"object":{"id":"cb5f559a-b039-5343-af6b-a473470f662d","slug":"human-mat1a-hypermethioninemia","display_name":"Hypermethioninemia in human MAT1A deficiency","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0f5933f9-e13f-5095-8cc4-817174037f62","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-mat1-loss-event","event_type":"observed_relationship","label":"High substrate can signal failure to process it.","description":"Reduced MAT I/III function caused persistent hypermethioninemia in patients with biallelic MAT1A variants.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7fdec12b-82f3-5c55-88fb-32428555c7c6","slug":"mat1a","display_name":"Human methionine adenosyltransferase 1A / MAT1A","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cb5f559a-b039-5343-af6b-a473470f662d","slug":"human-mat1a-hypermethioninemia","display_name":"Hypermethioninemia in human MAT1A deficiency","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"role":"context_participant","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_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Aggregated clinical data from 64 homozygous/compound-heterozygous patients.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not imply that high methionine always means this genetic disorder.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"High substrate can signal failure to process it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mudd's disease (MAT I/III deficiency): a survey of data for MAT1A homozygotes and compound heterozygotes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26289392/ · DOI 10.1186/s13023-015-0321-y","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":"54582d9e-b7ba-5c09-9c7d-b1ba5ab0b301","evidence_kind":"source_excerpt","locator":"Lines 156-162","start_line":156,"end_line":162,"excerpt":"## methionine-mat1-loss\nHigh substrate can signal failure to process it.\nReduced MAT I/III function caused persistent hypermethioninemia in patients with biallelic MAT1A variants.\nModel: Aggregated clinical data from 64 homozygous/compound-heterozygous patients.\nLimitations: Does not imply that high methionine always means this genetic disorder.\nEvidence access: Primary abstract\nMudd's disease (MAT I/III deficiency): a survey of data for MAT1A homozygotes and compound heterozygotes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26289392/ · DOI 10.1186/s13023-015-0321-y","model_system":"Aggregated clinical data from 64 homozygous/compound-heterozygous patients.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d969b004-ccc2-5bb4-9109-8ac649137ad1","stable_key":"import-41a89233-da9a-5b7b-9c18-e19bbadcfe2d","title":"L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; 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