{"id":"0c2b7f45-157f-5309-872c-b757b3e3200c","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-yrdc-inherited-disease","predicate":"when_mutated_causes","statement":"Inherited YRDC mutations were associated with severe Galloway–Mowat syndrome, linking t6A machinery impairment with microcephaly and early-onset nephrotic disease.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8f605d04-71cc-5b82-adfc-ad0557924ddc","mechanism_event_label":"A threonine-using RNA pathway matters in human brain and kidney development.","subject":{"id":"3114b5d2-04d2-59d6-88c3-c04eb28aeeff","slug":"yrdc","display_name":"Human threonylcarbamoyladenylate synthase / YRDC","entity_type_key":"protein"},"object":{"id":"79d71d4c-2b65-511d-9396-b972cdde5e55","slug":"human-yrdc-galloway-mowat","display_name":"YRDC-associated Galloway–Mowat syndrome","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8f605d04-71cc-5b82-adfc-ad0557924ddc","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-yrdc-inherited-disease-event","event_type":"observed_relationship","label":"A threonine-using RNA pathway matters in human brain and kidney development.","description":"Inherited YRDC mutations were associated with severe Galloway–Mowat syndrome, linking t6A machinery impairment with microcephaly and early-onset nephrotic disease.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3114b5d2-04d2-59d6-88c3-c04eb28aeeff","slug":"yrdc","display_name":"Human threonylcarbamoyladenylate synthase / YRDC","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"79d71d4c-2b65-511d-9396-b972cdde5e55","slug":"human-yrdc-galloway-mowat","display_name":"YRDC-associated Galloway–Mowat syndrome","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5c27b149-da7e-5a90-8bd3-d4b2a42bb2ef","slug":"trna-threonylcarbamoyladenosine","display_name":"tRNA-bound N6-threonylcarbamoyladenosine / t6A37","entity_type_key":"rna"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"f43067df-0574-5a5c-a228-eaf894752ac6","slug":"gon7","display_name":"Human KEOPS subunit / GON7","entity_type_key":"protein"},"role":"context_participant","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_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human genetic disease study with functional analyses; GON7-associated cases were milder in the reported series.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is an inherited machinery disorder, not demonstrated dietary threonine deficiency or a proven supplementation-responsive syndrome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A threonine-using RNA pathway matters in human brain and kidney development.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x","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":"7a382b3f-76b3-57d9-a8dc-cb7bb35b37da","evidence_kind":"source_excerpt","locator":"Lines 458-464","start_line":458,"end_line":464,"excerpt":"## l-threonine-yrdc-inherited-disease\nA threonine-using RNA pathway matters in human brain and kidney development.\nInherited YRDC mutations were associated with severe Galloway–Mowat syndrome, linking t6A machinery impairment with microcephaly and early-onset nephrotic disease.\nModel: Human genetic disease study with functional analyses; GON7-associated cases were milder in the reported series.\nLimitations: This is an inherited machinery disorder, not demonstrated dietary threonine deficiency or a proven supplementation-responsive syndrome.\nEvidence access: Primary abstract\nDefects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x","model_system":"Human genetic disease study with functional analyses; 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