{"id":"4122eb93-e7ca-56dc-80af-5a3fcd5d4210","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-pemt-esr-binding","predicate":"impairs","statement":"The studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1e588be9-527f-578c-a62b-e5ea88d63ba3","mechanism_event_label":"The hormone signal could not engage this regulatory site normally.","subject":{"id":"28a059ce-9fd3-54e8-ba3f-9cc58512b565","slug":"pemt-estrogen-risk-haplotype","display_name":"PEMT estrogen-response risk haplotype in the 2011 study","entity_type_key":"gene"},"object":{"id":"1d7bc09b-1c2b-54f3-80a8-34e0c1abc174","slug":"pemt-risk-estrogen-receptor-binding","display_name":"Estrogen-receptor binding at the PEMT risk haplotype","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1e588be9-527f-578c-a62b-e5ea88d63ba3","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-pemt-esr-binding-event","event_type":"biochemical_relationship","label":"The hormone signal could not engage this regulatory site normally.","description":"The studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a5acc0c5-f4ed-5b32-abfa-f9b27c025356","slug":"pemt","display_name":"Human phosphatidylethanolamine N-methyltransferase / PEMT","entity_type_key":"protein"},"role":"regulated_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b03c0784-d18d-58e3-99c5-2bcfed07028b","slug":"esr1","display_name":"Human estrogen receptor alpha / ESR1","entity_type_key":"protein"},"role":"regulatory_binding_protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"28a059ce-9fd3-54e8-ba3f-9cc58512b565","slug":"pemt-estrogen-risk-haplotype","display_name":"PEMT estrogen-response risk haplotype in the 2011 study","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1d7bc09b-1c2b-54f3-80a8-34e0c1abc174","slug":"pemt-risk-estrogen-receptor-binding","display_name":"Estrogen-receptor binding at the PEMT risk haplotype","entity_type_key":"cellular_process"},"role":"target","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_span","value_text":"{\"source_cache\": \"artifacts/choline-research/21059658.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\", \"start_char\": 0, \"end_char\": 1380, \"text_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transcript-specific expression, haplotype and chromatin-binding analyses","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Estrogen stimulation across PEMT haplotypes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Choline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The hormone signal could not engage this regulatory site normally.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Primary hepatocytes and PEMT regulatory locus","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":"39cd229c-93e4-57f0-8bfa-2a591332f3b5","evidence_kind":"source_excerpt","locator":"Lines 854-865","start_line":854,"end_line":865,"excerpt":"### choline-pemt-esr-binding\nThe studied risk allele failed to bind estrogen receptor at the critical PEMT regulatory region.\nCondition category: machinery_impairment\nnutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The hormone signal could not engage this regulatory site normally.\norganism: Human\ntissue_or_cell_type: Primary hepatocytes and PEMT regulatory locus\nexperimental_model: Transcript-specific expression, haplotype and chromatin-binding analyses\nlimitations: Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.\nexposure: Estrogen stimulation across PEMT haplotypes\nevidence_span: {\"source_cache\": \"artifacts/choline-research/21059658.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\", \"start_char\": 0, \"end_char\": 1380, \"text_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\"}\n[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. 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