{"id":"a943b429-29b3-5917-9d55-cb03e2e53246","stable_key":"00c24cfe-6189-5244-b81f-5d693e4e177d:chlorogenic_acid-slc37a4-loss","predicate":"impairs","statement":"Loss-of-function SLC37A4 variants impair the transport machinery associated with glycogen storage disease Ib.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ff2681c6-379b-5a0d-8606-3f68ac50a978","mechanism_event_label":"The same protein has a normal role and a distinct genetic failure state.","subject":{"id":"14d825e0-37bc-50fa-a186-d451ecf54464","slug":"slc37a4-loss-of-function","display_name":"Human SLC37A4 loss-of-function variants","entity_type_key":"protein_state"},"object":{"id":"fc2d8625-a3b5-5b7a-a535-7cbd2697932f","slug":"g6p-er-import","display_name":"Glucose-6-phosphate import into the endoplasmic reticulum","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ff2681c6-379b-5a0d-8606-3f68ac50a978","stable_key":"00c24cfe-6189-5244-b81f-5d693e4e177d:chlorogenic_acid-slc37a4-loss-event","event_type":"biochemical_relationship","label":"The same protein has a normal role and a distinct genetic failure state.","description":"Loss-of-function SLC37A4 variants impair the transport machinery associated with glycogen storage disease Ib.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3d1fc9ae-b00c-51e0-bf3a-c6cb0d10d458","slug":"slc37a4","display_name":"Human glucose-6-phosphate transporter / SLC37A4","entity_type_key":"protein"},"role":"affected_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"14d825e0-37bc-50fa-a186-d451ecf54464","slug":"slc37a4-loss-of-function","display_name":"Human SLC37A4 loss-of-function variants","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fc2d8625-a3b5-5b7a-a535-7cbd2697932f","slug":"g6p-er-import","display_name":"Glucose-6-phosphate import into the endoplasmic reticulum","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/chlorogenic_acid-research/42520004.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c05de010432b8bfaee87bdbba5f9fe93e7a262d41a17d19ec6e0b7b480e35ee6\", \"start_char\": 0, \"end_char\": 2009, \"text_sha256\": \"c05de010432b8bfaee87bdbba5f9fe93e7a262d41a17d19ec6e0b7b480e35ee6\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cryo-EM with biochemical transport and thermostability assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Apo, glucose-6-phosphate-bound and chlorogenic-acid-bound structures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Direct structural target evidence does not establish inhibition after ordinary food intake. Variant disease and compound exposure are different mechanisms; coffee does not thereby cause glycogen storage disease.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chlorogenic-acid","display_name":"Chlorogenic acid / 5-O-caffeoylquinic acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human recombinant SLC37A4","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The same protein has a normal role and a distinct genetic failure state.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chlorogenic_acid-p42520004] Structural basis for substrate recognition and inhibition of human glucose-6-phosphate transporter SLC37A4. (2026). https://pubmed.ncbi.nlm.nih.gov/42520004/ DOI: 10.1371/journal.pbio.3003833","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293-expressed transporter; purified membrane-protein preparation","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":"3f640e49-d65d-50d5-bada-fe201bc8e37d","evidence_kind":"source_excerpt","locator":"Lines 373-384","start_line":373,"end_line":384,"excerpt":"### chlorogenic_acid-slc37a4-loss\nLoss-of-function SLC37A4 variants impair the transport machinery associated with glycogen storage disease Ib.\nCondition category: machinery_impairment\nnutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The same protein has a normal role and a distinct genetic failure state.\norganism: Human recombinant SLC37A4\ntissue_or_cell_type: HEK293-expressed transporter; purified membrane-protein preparation\nexperimental_model: Cryo-EM with biochemical transport and thermostability assays\nlimitations: Direct structural target evidence does not establish inhibition after ordinary food intake. Variant disease and compound exposure are different mechanisms; coffee does not thereby cause glycogen storage disease.\nexposure: Apo, glucose-6-phosphate-bound and chlorogenic-acid-bound structures\nevidence_span: {\"source_cache\": \"artifacts/chlorogenic_acid-research/42520004.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c05de010432b8bfaee87bdbba5f9fe93e7a262d41a17d19ec6e0b7b480e35ee6\", \"start_char\": 0, \"end_char\": 2009, \"text_sha256\": \"c05de010432b8bfaee87bdbba5f9fe93e7a262d41a17d19ec6e0b7b480e35ee6\"}\n[chlorogenic_acid-p42520004] Structural basis for substrate recognition and inhibition of human glucose-6-phosphate transporter SLC37A4. 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