{"id":"5b22f7e8-d1d8-5a0c-b0f8-d12903d6586e","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-genetic-variation","predicate":"associated_with_reduced","statement":"CYP2A6 variant alleles were identified in individuals with poor coumarin metabolism, including a single-amino-acid inactivating variant.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e759ad0b-e467-524d-af7c-519633cf0ba8","mechanism_event_label":"Inherited enzyme differences can change how coumarin is processed.","subject":{"id":"4597c059-0718-5948-894c-7d7ee134a8c4","slug":"cyp2a6-1995-poor-metabolizer-alleles","display_name":"CYP2A6 variant alleles in the 1995 coumarin phenotyping study; original nomenclature retained","entity_type_key":"protein_state"},"object":{"id":"8a5084db-2b31-59a9-8afc-3ad0980d8f5d","slug":"coumarin-7-hydroxylation","display_name":"Coumarin 7-hydroxylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e759ad0b-e467-524d-af7c-519633cf0ba8","stable_key":"f812c44f-d0fd-5f01-ba2c-748c0794fcfb:coumarin-genetic-variation-event","event_type":"biochemical_relationship","label":"Inherited enzyme differences can change how coumarin is processed.","description":"CYP2A6 variant alleles were identified in individuals with poor coumarin metabolism, including a single-amino-acid inactivating variant.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4597c059-0718-5948-894c-7d7ee134a8c4","slug":"cyp2a6-1995-poor-metabolizer-alleles","display_name":"CYP2A6 variant alleles in the 1995 coumarin phenotyping study; original nomenclature retained","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8a5084db-2b31-59a9-8afc-3ad0980d8f5d","slug":"coumarin-7-hydroxylation","display_name":"Coumarin 7-hydroxylation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coumarin-research/7668294.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1\", \"start_char\": 0, \"end_char\": 1316, \"text_sha256\": \"aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"CYP2A gene sequencing and coumarin metabolic phenotyping","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Original CYP2A6v1/v2 nomenclature; poor-metabolizer individuals","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Historical variant labels retained; no automatic mapping to modern star alleles and no demonstrated prediction of liver injury.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coumarin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coumarin","display_name":"Coumarin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Inherited enzyme differences can change how coumarin is processed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coumarin-p7668294] A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. (1995). https://pubmed.ncbi.nlm.nih.gov/7668294/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Genomic DNA and whole-body probe metabolism","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":"8459137c-651e-5fd2-904b-d327d5a046cb","evidence_kind":"source_excerpt","locator":"Lines 631-642","start_line":631,"end_line":642,"excerpt":"### coumarin-genetic-variation\nCYP2A6 variant alleles were identified in individuals with poor coumarin metabolism, including a single-amino-acid inactivating variant.\nCondition category: machinery_impairment\nnutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Inherited enzyme differences can change how coumarin is processed.\norganism: Human\ntissue_or_cell_type: Genomic DNA and whole-body probe metabolism\nexperimental_model: CYP2A gene sequencing and coumarin metabolic phenotyping\nlimitations: Historical variant labels retained; no automatic mapping to modern star alleles and no demonstrated prediction of liver injury.\nexposure: Original CYP2A6v1/v2 nomenclature; poor-metabolizer individuals\nevidence_span: {\"source_cache\": \"artifacts/coumarin-research/7668294.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1\", \"start_char\": 0, \"end_char\": 1316, \"text_sha256\": \"aeb377e6bbda1a552066c5d1caf1bf558753096627b863835637a0f2f942b3b1\"}\n[coumarin-p7668294] A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. 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