{"id":"c8f3f417-23db-5ce0-831b-db53173296aa","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pah-variant","predicate":"loses_regulatory_response_in","statement":"The disease-associated E76A regulatory-domain mutant showed reduced phenylalanine binding, dimerization and stability.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"2260c27b-2a44-5eef-aae5-51e4d6ef5471","mechanism_event_label":"A PAH variant can damage the substrate-sensing switch.","subject":{"id":"ea908671-6f85-5342-abe4-1a466a3b0572","slug":"pah","display_name":"Human phenylalanine hydroxylase / PAH","entity_type_key":"protein"},"object":{"id":"c4a17882-7343-5e43-8c58-6f09891b6f7d","slug":"pah-e76a-regulatory-response","display_name":"Human PAH E76A regulatory-domain response","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2260c27b-2a44-5eef-aae5-51e4d6ef5471","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pah-variant-event","event_type":"observed_relationship","label":"A PAH variant can damage the substrate-sensing switch.","description":"The disease-associated E76A regulatory-domain mutant showed reduced phenylalanine binding, dimerization and stability.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ea908671-6f85-5342-abe4-1a466a3b0572","slug":"pah","display_name":"Human phenylalanine hydroxylase / PAH","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c4a17882-7343-5e43-8c58-6f09891b6f7d","slug":"pah-e76a-regulatory-response","display_name":"Human PAH E76A regulatory-domain response","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","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 full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human PAH regulatory-domain E76A comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Domain behavior does not quantify whole-body phenylalanine clearance for every PAH variant.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A PAH variant can damage the substrate-sensing switch.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748","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":"36501f2c-e8d5-550d-89fa-fff3a55c388b","evidence_kind":"source_excerpt","locator":"Lines 30-36","start_line":30,"end_line":36,"excerpt":"## l-phenylalanine-pah-variant\nA PAH variant can damage the substrate-sensing switch.\nThe disease-associated E76A regulatory-domain mutant showed reduced phenylalanine binding, dimerization and stability.\nModel: Purified human PAH regulatory-domain E76A comparison.\nLimitations: Domain behavior does not quantify whole-body phenylalanine clearance for every PAH variant.\nEvidence access: Primary full text\nStructural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748","model_system":"Purified human PAH regulatory-domain E76A comparison.","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":"54de7c56-1e60-5d7b-8ef9-852c58ae92ba","stable_key":"import-56f1d914-e7da-595a-af69-c217b2b47407","title":"L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; 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