{"id":"4ceda28b-2300-5bb4-8fd2-560fff6e8afc","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-wnk3-potassium","predicate":"inhibits","statement":"Mutation of the corresponding WNK3 E314 site reduced potassium inhibition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ab853703-c255-59d6-8992-44ff0f02a069","mechanism_event_label":"The direct potassium-sensitive route also has evidence in WNK3.","subject":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"object":{"id":"b1dea1b1-2a97-5604-9e4f-f12d47d6b9ca","slug":"wnk3","display_name":"Human WNK lysine deficient protein kinase 3 / WNK3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ab853703-c255-59d6-8992-44ff0f02a069","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-wnk3-potassium-event","event_type":"biochemical_relationship","label":"The direct potassium-sensitive route also has evidence in WNK3.","description":"Mutation of the corresponding WNK3 E314 site reduced potassium inhibition.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b1dea1b1-2a97-5604-9e4f-f12d47d6b9ca","slug":"wnk3","display_name":"Human WNK lysine deficient protein kinase 3 / WNK3","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/chloride-research/42186973.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa\", \"start_char\": 0, \"end_char\": 1266, \"text_sha256\": \"2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Crystallography and mutagenesis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cesium surrogate and potassium-inhibition assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chloride research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chloride","display_name":"Chloride","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human WNK1/WNK3 constructs","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The direct potassium-sensitive route also has evidence in WNK3.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. (2026). https://pubmed.ncbi.nlm.nih.gov/42186973/ DOI: 10.1021/acs.biochem.5c00825","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified kinase domains","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"201bd980-315d-5971-8a31-918bacda7a9b","evidence_kind":"source_excerpt","locator":"Lines 380-391","start_line":380,"end_line":391,"excerpt":"### chloride-wnk3-potassium\nMutation of the corresponding WNK3 E314 site reduced potassium inhibition.\nCondition category: normal\nnutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The direct potassium-sensitive route also has evidence in WNK3.\norganism: Human WNK1/WNK3 constructs\ntissue_or_cell_type: Purified kinase domains\nexperimental_model: Crystallography and mutagenesis\nlimitations: Surrogate binding plus functional mutagenesis; not dietary potassium dosing or replacement of chloride sensing.\nexposure: Cesium surrogate and potassium-inhibition assays\nevidence_span: {\"source_cache\": \"artifacts/chloride-research/42186973.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa\", \"start_char\": 0, \"end_char\": 1266, \"text_sha256\": \"2499194159ba661c04fab5e89f45495e428fe64b36b14b81940fb42b52853afa\"}\n[chloride-p42186973] Structural Basis for Potassium Inhibition of WNK Kinases. 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