{"id":"2f18f919-3151-554e-8abe-9bdc79e2c368","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-human-gpt2-variants","predicate":"impair","statement":"The human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"eda06526-9933-5a5e-8b34-732d0485aae6","mechanism_event_label":"A genetic defect in alanine-related metabolism can affect brain growth and movement.","subject":{"id":"97f5cebc-dbab-5fd9-931a-0f44ad5cac4c","slug":"human-gpt2-loss-variants","display_name":"Human recessive GPT2 loss-of-function variants","entity_type_key":"cellular_process"},"object":{"id":"59baef49-fed8-5b6f-90ca-b8efdf021608","slug":"gpt2","display_name":"Human mitochondrial alanine aminotransferase / GPT2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"eda06526-9933-5a5e-8b34-732d0485aae6","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-human-gpt2-variants-event","event_type":"observed_relationship","label":"A genetic defect in alanine-related metabolism can affect brain growth and movement.","description":"The human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"97f5cebc-dbab-5fd9-931a-0f44ad5cac4c","slug":"human-gpt2-loss-variants","display_name":"Human recessive GPT2 loss-of-function variants","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"59baef49-fed8-5b6f-90ca-b8efdf021608","slug":"gpt2","display_name":"Human mitochondrial alanine aminotransferase / GPT2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"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 families plus biochemical variant assays; accompanying mouse metabolic experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Clinical association and enzyme loss do not establish that low dietary alanine caused the phenotype or that supplementation treats it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A genetic defect in alanine-related metabolism can affect brain growth and movement.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27601654/ · DOI 10.1073/pnas.1609221113","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":"7d7964fa-2a18-517c-a805-405ad947bc5a","evidence_kind":"source_excerpt","locator":"Lines 296-302","start_line":296,"end_line":302,"excerpt":"## alanine-human-gpt2-variants\nA genetic defect in alanine-related metabolism can affect brain growth and movement.\nThe human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms.\nModel: Human families plus biochemical variant assays; accompanying mouse metabolic experiments.\nLimitations: Clinical association and enzyme loss do not establish that low dietary alanine caused the phenotype or that supplementation treats it.\nEvidence access: Primary abstract\nMutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27601654/ · DOI 10.1073/pnas.1609221113","model_system":"Human families plus biochemical variant assays; accompanying mouse metabolic experiments.","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":"01c5554c-a8ba-5c86-9b01-a0fa1a886cdb","stable_key":"import-10aa417f-4b03-599f-a453-4aa09edeb27c","title":"L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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