{"id":"f9b94311-19e2-5f2c-b511-67068e3eee10","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-cht1-mutants","predicate":"impairs","statement":"Tested SLC5A7 missense variants caused a near-complete loss of CHT transport activity in cell models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"95848ab4-ccd2-51c3-80f1-e817b0bff5bb","mechanism_event_label":"A damaged transporter can interrupt acetylcholine supply upstream of the synthesis enzyme.","subject":{"id":"f04f8c3b-f0fc-53bb-96e4-8038c5cd0ea3","slug":"slc5a7-2016-missense-variants","display_name":"Human SLC5A7 missense variants tested in the 2016 CMS study","entity_type_key":"protein_set"},"object":{"id":"698875f9-8800-5abc-ba9c-9b6fcc2628b2","slug":"human-cht1-choline-uptake","display_name":"Human CHT1-mediated choline uptake in expression assays","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"95848ab4-ccd2-51c3-80f1-e817b0bff5bb","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-cht1-mutants-event","event_type":"biochemical_relationship","label":"A damaged transporter can interrupt acetylcholine supply upstream of the synthesis enzyme.","description":"Tested SLC5A7 missense variants caused a near-complete loss of CHT transport activity in cell models.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"04646285-c618-515d-8baa-57f7805cf6c0","slug":"slc5a7","display_name":"Human high-affinity choline transporter CHT1 / SLC5A7","entity_type_key":"protein"},"role":"affected_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f04f8c3b-f0fc-53bb-96e4-8038c5cd0ea3","slug":"slc5a7-2016-missense-variants","display_name":"Human SLC5A7 missense variants tested in the 2016 CMS study","entity_type_key":"protein_set"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"698875f9-8800-5abc-ba9c-9b6fcc2628b2","slug":"human-cht1-choline-uptake","display_name":"Human CHT1-mediated choline uptake in expression assays","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/27569547.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d\", \"start_char\": 0, \"end_char\": 1723, \"text_sha256\": \"8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Six-family genetics, expression assays and NMJ examination","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Eleven recessive SLC5A7 mutations; missense variants tested functionally","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rare inherited disease with variant-specific effects; not a dietary-deficiency diagnosis or evidence that supplements repair the transporter.","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 variants; cell expression systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A damaged transporter can interrupt acetylcholine supply upstream of the synthesis enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[choline-p27569547] Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. (2016). https://pubmed.ncbi.nlm.nih.gov/27569547/ DOI: 10.1016/j.ajhg.2016.06.033","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Neuromuscular junction and choline transport","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":"b0e9ba2b-ee13-5190-b1d3-ed659736a82b","evidence_kind":"source_excerpt","locator":"Lines 347-358","start_line":347,"end_line":358,"excerpt":"### choline-cht1-mutants\nTested SLC5A7 missense variants caused a near-complete loss of CHT transport activity in cell models.\nCondition category: machinery_impairment\nnutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A damaged transporter can interrupt acetylcholine supply upstream of the synthesis enzyme.\norganism: Human variants; cell expression systems\ntissue_or_cell_type: Neuromuscular junction and choline transport\nexperimental_model: Six-family genetics, expression assays and NMJ examination\nlimitations: Rare inherited disease with variant-specific effects; not a dietary-deficiency diagnosis or evidence that supplements repair the transporter.\nexposure: Eleven recessive SLC5A7 mutations; missense variants tested functionally\nevidence_span: {\"source_cache\": \"artifacts/choline-research/27569547.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d\", \"start_char\": 0, \"end_char\": 1723, \"text_sha256\": \"8f8b3acd919795de1aa33ccb5a616ccaaffc27e619990562f1bb69add7836d3d\"}\n[choline-p27569547] Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. (2016). https://pubmed.ncbi.nlm.nih.gov/27569547/ DOI: 10.1016/j.ajhg.2016.06.033","model_system":"Six-family genetics, expression assays and NMJ examination","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [choline-p27569547] Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. (2016). https://pubmed.ncbi.nlm.nih.gov/27569547/ DOI: 10.1016/j.ajhg.2016.06.033","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0ba2f05e-5cf5-5bd7-ae5d-0ab4945fcb7b","stable_key":"import-27e0c1cf-7726-5164-8b15-27a631584cd0","title":"Choline: metabolism, signaling and nutrient connections (2026-09-17)","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":"c7afe3d579eba0df6d2a4c26699c653462749e03188348f900c07748cc7282a8","revision_id":"0fa7b48f-2a3c-5adc-b13e-48727dd6f815","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}