{"id":"b8657b28-83b8-5a96-bbc7-89b0f1ca61ea","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-transporter-brain-loss","predicate":"loss_depleted","statement":"The SLC6A8-deficient male had absent brain creatine on spectroscopy and defective fibroblast creatine uptake despite high plasma and urinary creatine and normal guanidinoacetate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"99e39430-bff7-5228-961c-63203a5214a9","mechanism_event_label":"A high blood or urine value did not mean creatine reached the brain.","subject":{"id":"75fe55a3-ff87-5cbd-bb76-e808421fa627","slug":"slc6a8","display_name":"Human creatine transporter CRT / SLC6A8","entity_type_key":"protein"},"object":{"id":"c6071833-4355-5a87-9123-8cc3d12c9bb4","slug":"brain-total-creatine","display_name":"Brain total creatine concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"99e39430-bff7-5228-961c-63203a5214a9","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-transporter-brain-loss-event","event_type":"biochemical_relationship","label":"A high blood or urine value did not mean creatine reached the brain.","description":"The SLC6A8-deficient male had absent brain creatine on spectroscopy and defective fibroblast creatine uptake despite high plasma and urinary creatine and normal guanidinoacetate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9f5df558-ed3d-5cda-b5ca-0f90f7aa6a8c","slug":"creatine","display_name":"Creatine","entity_type_key":"small_molecule"},"role":"poorly_transported_metabolite","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"84053a83-8fcc-5068-8df9-58f7e97fad76","slug":"guanidinoacetate","display_name":"Guanidinoacetate","entity_type_key":"small_molecule"},"role":"normal_precursor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"75fe55a3-ff87-5cbd-bb76-e808421fa627","slug":"slc6a8","display_name":"Human creatine transporter CRT / SLC6A8","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c6071833-4355-5a87-9123-8cc3d12c9bb4","slug":"brain-total-creatine","display_name":"Brain total creatine concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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/creatine-research/11326334.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9\", \"start_char\": 0, \"end_char\": 739, \"text_sha256\": \"95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human family genetics and fibroblast transport assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SLC6A8 loss-of-function variant","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Single family; circulating creatine cannot substitute for cellular transport. No treatment failure claim is inferred from this abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Creatine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"creatine","display_name":"Creatine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human male patient and relatives","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A high blood or urine value did not mean creatine reached the brain.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[creatine-p11326334] X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. (2001). https://pubmed.ncbi.nlm.nih.gov/11326334/ DOI: 10.1086/320595","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Brain spectroscopy, plasma, urine and fibroblasts","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":"3623c44d-7175-5712-beac-e871d400c9d2","evidence_kind":"source_excerpt","locator":"Lines 906-917","start_line":906,"end_line":917,"excerpt":"### creatine-transporter-brain-loss\nThe SLC6A8-deficient male had absent brain creatine on spectroscopy and defective fibroblast creatine uptake despite high plasma and urinary creatine and normal guanidinoacetate.\nCondition category: machinery_impairment\nnutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A high blood or urine value did not mean creatine reached the brain.\norganism: Human male patient and relatives\ntissue_or_cell_type: Brain spectroscopy, plasma, urine and fibroblasts\nexperimental_model: Human family genetics and fibroblast transport assay\nlimitations: Single family; circulating creatine cannot substitute for cellular transport. No treatment failure claim is inferred from this abstract.\nexposure: SLC6A8 loss-of-function variant\nevidence_span: {\"source_cache\": \"artifacts/creatine-research/11326334.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9\", \"start_char\": 0, \"end_char\": 739, \"text_sha256\": \"95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9\"}\n[creatine-p11326334] X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. (2001). https://pubmed.ncbi.nlm.nih.gov/11326334/ DOI: 10.1086/320595","model_system":"Human family genetics and fibroblast transport assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [creatine-p11326334] X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. (2001). https://pubmed.ncbi.nlm.nih.gov/11326334/ DOI: 10.1086/320595","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"70358046-c5c3-5e9a-9fc9-eb01c3fff88b","stable_key":"import-44737fa3-b335-53f4-a644-b9878d4416ac","title":"Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (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":"548237d3e98a73a7dc02181807921fdd8b902adcee46248792258a761593eda9","revision_id":"88738255-8028-52fb-9c12-0fe92d8ce367","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}