{"id":"e29f67a1-6754-5211-b3fa-7cec16776ae3","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-chkb-activity","predicate":"reduces","statement":"Choline kinase activity was undetectable in the three reported muscle samples with CHKB nonsense variants.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7ca59554-a6cd-5c34-9cc8-1c4f924e714d","mechanism_event_label":"The first phosphorylation step was severely impaired.","subject":{"id":"e9b93a74-8997-5e2f-912c-868dc72cb101","slug":"chkb-2011-nonsense-genotypes","display_name":"CHKB nonsense genotypes in the three 2011 muscle assays","entity_type_key":"protein_state"},"object":{"id":"0e81832f-d2cd-531f-83e2-1ffebbd1539c","slug":"human-chkb-muscle-activity","display_name":"Muscle choline kinase activity in CHKB-deficient individuals","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7ca59554-a6cd-5c34-9cc8-1c4f924e714d","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-chkb-activity-event","event_type":"biochemical_relationship","label":"The first phosphorylation step was severely impaired.","description":"Choline kinase activity was undetectable in the three reported muscle samples with CHKB nonsense variants.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"050aab7c-4b07-5e0c-a46e-a0d9a5371ab1","slug":"chkb","display_name":"Human choline kinase beta / CHKB","entity_type_key":"protein"},"role":"affected_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e9b93a74-8997-5e2f-912c-868dc72cb101","slug":"chkb-2011-nonsense-genotypes","display_name":"CHKB nonsense genotypes in the three 2011 muscle assays","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0e81832f-d2cd-531f-83e2-1ffebbd1539c","slug":"human-chkb-muscle-activity","display_name":"Muscle choline kinase activity in CHKB-deficient individuals","entity_type_key":"cellular_process"},"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/choline-research/21665002.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f\", \"start_char\": 0, \"end_char\": 1157, \"text_sha256\": \"ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Fifteen affected individuals with CHKB variants; muscle assays in three","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biallelic CHKB variants; three nonsense-genotype muscle samples","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A congenital enzyme defect, distinct from ordinary nutrient depletion; mitochondrial morphology does not prove one unique downstream lesion.","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 first phosphorylation step was severely impaired.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[choline-p21665002] A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. (2011). https://pubmed.ncbi.nlm.nih.gov/21665002/ DOI: 10.1016/j.ajhg.2011.05.010","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Skeletal muscle","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":"eb35aa01-588f-5533-8cd3-4e882f05470e","evidence_kind":"source_excerpt","locator":"Lines 711-722","start_line":711,"end_line":722,"excerpt":"### choline-chkb-activity\nCholine kinase activity was undetectable in the three reported muscle samples with CHKB nonsense variants.\nCondition category: machinery_impairment\nnutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The first phosphorylation step was severely impaired.\norganism: Human\ntissue_or_cell_type: Skeletal muscle\nexperimental_model: Fifteen affected individuals with CHKB variants; muscle assays in three\nlimitations: A congenital enzyme defect, distinct from ordinary nutrient depletion; mitochondrial morphology does not prove one unique downstream lesion.\nexposure: Biallelic CHKB variants; three nonsense-genotype muscle samples\nevidence_span: {\"source_cache\": \"artifacts/choline-research/21665002.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f\", \"start_char\": 0, \"end_char\": 1157, \"text_sha256\": \"ccd6913be10435c076cc81d7ea0509678751d445078c857bb977497a3754059f\"}\n[choline-p21665002] A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis. 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