{"id":"81163e14-7b13-5e12-b260-e57147246abf","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-aldh2-allele-dominant","predicate":"reduces","statement":"The inactive ALDH2 subunit carries a substitution of lysine for glutamate at position 487, and correlating genotype with phenotype in 24 Japanese livers shows the allele encoding the abnormal subunit is dominant.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"27a5a8a3-165f-559f-99ae-3a3363726246","mechanism_event_label":"One bad copy is enough, because the faulty subunit poisons the four-part enzyme.","subject":{"id":"64badd5b-0769-5c6f-b2c5-71dc92db5588","slug":"aldh2-glu487lys","display_name":"The inactive ALDH2*2 subunit carrying lysine for glutamate at position 487","entity_type_key":"protein_state"},"object":{"id":"40b7767f-2ff9-570b-b0ed-77b11ed08901","slug":"aldh2","display_name":"Human mitochondrial aldehyde dehydrogenase 2 / ALDH2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"27a5a8a3-165f-559f-99ae-3a3363726246","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-aldh2-allele-dominant-event","event_type":"biochemical_relationship","label":"One bad copy is enough, because the faulty subunit poisons the four-part enzyme.","description":"The inactive ALDH2 subunit carries a substitution of lysine for glutamate at position 487, and correlating genotype with phenotype in 24 Japanese livers shows the allele encoding the abnormal subunit is dominant.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5fa32382-7b38-5a03-aa8a-168d01358750","slug":"acetaldehyde","display_name":"Acetaldehyde","entity_type_key":"small_molecule"},"role":"uncleared_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"64badd5b-0769-5c6f-b2c5-71dc92db5588","slug":"aldh2-glu487lys","display_name":"The inactive ALDH2*2 subunit carrying lysine for glutamate at position 487","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"40b7767f-2ff9-570b-b0ed-77b11ed08901","slug":"aldh2","display_name":"Human mitochondrial aldehyde dehydrogenase 2 / ALDH2","entity_type_key":"protein"},"role":"target","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_span","value_text":"{\"source_cache\": \"artifacts/alcohol-research/2562960.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1\", \"start_char\": 0, \"end_char\": 800, \"text_sha256\": \"0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ALDH2 genotype compared with measured enzyme activity","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Establishes dominance of the inactive allele, so heterozygotes are affected. The sample is 24 livers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ethanol","display_name":"Ethanol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"One bad copy is enough, because the faulty subunit poisons the four-part enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver","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":"7e462318-cdb3-5cec-b009-1a0fb99eb9e8","evidence_kind":"source_excerpt","locator":"Lines 150-161","start_line":150,"end_line":161,"excerpt":"### alcohol-aldh2-allele-dominant\nThe inactive ALDH2 subunit carries a substitution of lysine for glutamate at position 487, and correlating genotype with phenotype in 24 Japanese livers shows the allele encoding the abnormal subunit is dominant.\nCondition category: machinery_impairment\nnutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes.\nplain_language: One bad copy is enough, because the faulty subunit poisons the four-part enzyme.\norganism: Human\ntissue_or_cell_type: Liver\nexperimental_model: Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype\nlimitations: Establishes dominance of the inactive allele, so heterozygotes are affected. The sample is 24 livers.\nexposure: ALDH2 genotype compared with measured enzyme activity\nevidence_span: {\"source_cache\": \"artifacts/alcohol-research/2562960.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1\", \"start_char\": 0, \"end_char\": 800, \"text_sha256\": \"0f0722fad2747c7b723bce352582f07519b1b9b964edadb8674740458475efe1\"}\n[alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875","model_system":"Polymerase chain reaction genotyping of 24 Japanese livers against enzyme phenotype","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [alcohol-p2562960] Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. (1989). https://pubmed.ncbi.nlm.nih.gov/2562960/ DOI: 10.1172/jci113875","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4b310db0-1387-548c-9e3d-6d2ed634b2cd","stable_key":"import-fcc4fa9c-4dc8-5566-b780-1a486c4d3e72","title":"Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"cb7e8dc390e8bf302cd5e230cadff6ce9847b4aad8a3691a308964d93ba59a85","revision_id":"4b344e1e-4129-579c-a058-50262b03f9a8","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}