{"id":"7515bc5a-a3c2-5c54-a24c-b90f694226dd","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pcbd-mutants","predicate":"can_lose_coactivation_of","statement":"Five of seven tested PCBD1 mutations caused proteolytic instability and reduced FXYD2 promoter activity.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e168cdee-4ab7-56bd-bdaa-969bd80a25ff","mechanism_event_label":"Some mutations damage the protein and weaken its kidney-related transcriptional function.","subject":{"id":"a69cefc1-302d-5b87-8499-ecbe52b4059e","slug":"pcbd1","display_name":"Human pterin-4-alpha-carbinolamine dehydratase / PCBD1","entity_type_key":"protein"},"object":{"id":"56bd9a20-0c4b-508c-89a7-1195084827fd","slug":"fxyd2","display_name":"Human sodium/potassium ATPase regulatory subunit / FXYD2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"e168cdee-4ab7-56bd-bdaa-969bd80a25ff","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-pcbd-mutants-event","event_type":"observed_relationship","label":"Some mutations damage the protein and weaken its kidney-related transcriptional function.","description":"Five of seven tested PCBD1 mutations caused proteolytic instability and reduced FXYD2 promoter activity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a69cefc1-302d-5b87-8499-ecbe52b4059e","slug":"pcbd1","display_name":"Human pterin-4-alpha-carbinolamine dehydratase / PCBD1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"56bd9a20-0c4b-508c-89a7-1195084827fd","slug":"fxyd2","display_name":"Human sodium/potassium ATPase regulatory subunit / FXYD2","entity_type_key":"protein"},"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":""},{"entity":{"id":"da9042c2-976d-5bbc-af38-979e07906c49","slug":"hnf1b","display_name":"Human hepatocyte nuclear factor 1 beta / HNF1B","entity_type_key":"protein"},"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":"Human PCBD1 variant expression and promoter assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Variant effects are not uniform and do not establish dietary phenylalanine deficiency.","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":"Some mutations damage the protein and weaken its kidney-related transcriptional function.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24204001/ · DOI 10.1681/ASN.2013040337","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":"70e70783-1229-5522-886b-fe4703b46209","evidence_kind":"source_excerpt","locator":"Lines 86-92","start_line":86,"end_line":92,"excerpt":"## l-phenylalanine-pcbd-mutants\nSome mutations damage the protein and weaken its kidney-related transcriptional function.\nFive of seven tested PCBD1 mutations caused proteolytic instability and reduced FXYD2 promoter activity.\nModel: Human PCBD1 variant expression and promoter assays.\nLimitations: Variant effects are not uniform and do not establish dietary phenylalanine deficiency.\nEvidence access: Primary abstract\nMutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24204001/ · DOI 10.1681/ASN.2013040337","model_system":"Human PCBD1 variant expression and promoter assays.","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; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"4d53adcd4acc7a9aecf44ccb2623ec540c9d221a0f7c00002585870b39b8ffb8","revision_id":"fd182a81-4ab7-559a-9c77-fb4cf72982ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}