{"id":"98034864-2ba0-5dc5-923f-4bf4f68c7fc2","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-fah-genetic","predicate":"when_variant_disrupts","statement":"In 13 unrelated hereditary-tyrosinemia-I families, FAH nonsense variants reduced transcript abundance and splice-site variants altered exon inclusion.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"050ad859-0024-538b-a932-0b9a464813dc","mechanism_event_label":"The disease can arise before a functional enzyme is made.","subject":{"id":"aa4c2d18-df13-59ea-9ff3-5f7f9c3e0510","slug":"fah","display_name":"Human fumarylacetoacetate hydrolase / FAH","entity_type_key":"protein"},"object":{"id":"293b8280-e6ea-5953-996f-aaecdbd1593f","slug":"human-fah-transcripts","display_name":"Human FAH transcript abundance and splicing","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"050ad859-0024-538b-a932-0b9a464813dc","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-fah-genetic-event","event_type":"observed_relationship","label":"The disease can arise before a functional enzyme is made.","description":"In 13 unrelated hereditary-tyrosinemia-I families, FAH nonsense variants reduced transcript abundance and splice-site variants altered exon inclusion.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"aa4c2d18-df13-59ea-9ff3-5f7f9c3e0510","slug":"fah","display_name":"Human fumarylacetoacetate hydrolase / FAH","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"293b8280-e6ea-5953-996f-aaecdbd1593f","slug":"human-fah-transcripts","display_name":"Human FAH transcript abundance and splicing","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bcfef85f-831d-5439-ba51-1aef4b090441","slug":"l-tyrosine","display_name":"L-Tyrosine","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 family genotyping and RNA analysis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No strict genotype-severity relationship was established in this series.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The disease can arise before a functional enzyme is made.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8557261/ · DOI 10.1007/BF00218833","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":"1ab2af66-6097-560d-b19c-b5132176001f","evidence_kind":"source_excerpt","locator":"Lines 276-282","start_line":276,"end_line":282,"excerpt":"## l-tyrosine-fah-genetic\nThe disease can arise before a functional enzyme is made.\nIn 13 unrelated hereditary-tyrosinemia-I families, FAH nonsense variants reduced transcript abundance and splice-site variants altered exon inclusion.\nModel: Human family genotyping and RNA analysis.\nLimitations: No strict genotype-severity relationship was established in this series.\nEvidence access: Primary abstract\nHereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8557261/ · DOI 10.1007/BF00218833","model_system":"Human family genotyping and RNA analysis.","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":"12917df2-c6e0-5b61-850f-dbff6d4b4d30","stable_key":"import-63ce713e-6aea-59f6-9896-ca30e010b2ce","title":"L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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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