{"id":"d1827b0a-5554-5e7a-a218-d83bc15cbf14","stable_key":"507ed066-fd6d-5722-9223-97b66302e7e3:glycine-glyr-variant","predicate":"reduces_tested","statement":"Human alpha1(K276E)/beta receptors expressed in Xenopus oocytes were about 29-fold less glycine-sensitive than wild type and had shorter channel openings.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3e971443-4977-5b88-947b-0d9db44d9f13","mechanism_event_label":"The receptor can respond poorly even when its ligand is supplied.","subject":{"id":"de544344-5fae-5c72-8a81-031310d835c6","slug":"human-glra1-k276e-glrb","display_name":"Human alpha1(K276E)/beta glycine receptor","entity_type_key":"protein_complex"},"object":{"id":"4eee3915-aa86-57cb-bfee-a045c6a295f3","slug":"human-glyr-glycine-sensitivity","display_name":"Human glycine-receptor response to glycine","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3e971443-4977-5b88-947b-0d9db44d9f13","stable_key":"507ed066-fd6d-5722-9223-97b66302e7e3:glycine-glyr-variant-event","event_type":"observed_relationship","label":"The receptor can respond poorly even when its ligand is supplied.","description":"Human alpha1(K276E)/beta receptors expressed in Xenopus oocytes were about 29-fold less glycine-sensitive than wild type and had shorter channel openings.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"de544344-5fae-5c72-8a81-031310d835c6","slug":"human-glra1-k276e-glrb","display_name":"Human alpha1(K276E)/beta glycine receptor","entity_type_key":"protein_complex"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4eee3915-aa86-57cb-bfee-a045c6a295f3","slug":"human-glyr-glycine-sensitivity","display_name":"Human glycine-receptor response to glycine","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2b507258-430c-51fe-9fd2-e510c2c197a9","slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4ed6d982-40c6-5748-9157-273da25abe35","slug":"glra1","display_name":"Human glycine receptor alpha1 / GLRA1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"79f60cc6-19fe-59e6-a531-0b6ece776998","slug":"glrb","display_name":"Human glycine receptor beta / GLRB","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"6f35aa38-f875-5759-b749-97a2f6480ff3","slug":"chloride-ion","display_name":"Chloride ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Modeling implicated impaired gating rather than simply loss of ligand binding; not dietary glycine deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The receptor can respond poorly even when its ligand is supplied.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9490812/ · DOI 10.1111/j.1469-7793.1998.025bu.x","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":"13e88af9-1bb6-565b-94ca-cf0a8cfeddc5","evidence_kind":"source_excerpt","locator":"Lines 210-216","start_line":210,"end_line":216,"excerpt":"## glycine-glyr-variant\nThe receptor can respond poorly even when its ligand is supplied.\nHuman alpha1(K276E)/beta receptors expressed in Xenopus oocytes were about 29-fold less glycine-sensitive than wild type and had shorter channel openings.\nModel: Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording.\nLimitations: Modeling implicated impaired gating rather than simply loss of ligand binding; not dietary glycine deficiency.\nEvidence access: Primary abstract\nProperties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9490812/ · DOI 10.1111/j.1469-7793.1998.025bu.x","model_system":"Human disease-associated receptor constructs in frog oocytes; 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