{"id":"1d36d535-dc81-539b-ba1a-da17f7203cc2","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-slc25a19-human-pool-separation","predicate":"reduces","statement":"G177A patient lymphoblasts had approximately tenfold lower mitochondrial ThDP despite modestly increased cytosolic ThDP.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"bf771711-d847-5f10-afb1-331e1e9f99bf","mechanism_event_label":"B1 cofactor can remain outside mitochondria when its carrier fails.","subject":{"id":"b76b1905-b296-5b65-8123-24f2123b870e","slug":"slc25a19-g177a-genotype","display_name":"SLC25A19 G177A homozygous genotype","entity_type_key":"gene"},"object":{"id":"2509140a-9c3c-5965-a1fa-3022bb76e77a","slug":"mitochondrial-thdp-content","display_name":"Mitochondrial thiamine diphosphate content","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bf771711-d847-5f10-afb1-331e1e9f99bf","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-slc25a19-human-pool-separation-event","event_type":"observed_intervention","label":"B1 cofactor can remain outside mitochondria when its carrier fails.","description":"G177A patient lymphoblasts had approximately tenfold lower mitochondrial ThDP despite modestly increased cytosolic ThDP.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3f719fb0-6cf0-574a-a56f-3c43dfcb681a","slug":"slc25a19","display_name":"Human mitochondrial thiamine diphosphate transporter / SLC25A19","entity_type_key":"protein"},"role":"affected carrier","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"measured species","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b76b1905-b296-5b65-8123-24f2123b870e","slug":"slc25a19-g177a-genotype","display_name":"SLC25A19 G177A homozygous genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2509140a-9c3c-5965-a1fa-3022bb76e77a","slug":"mitochondrial-thdp-content","display_name":"Mitochondrial thiamine diphosphate content","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-scope","value_text":"Patient lymphoblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Table 1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/thiamine_transport_sources/PMC1595310.txt\", \"start_char\": 14675, \"end_char\": 15382}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cultured lymphoblast fractions; not a plasma threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"B1 cofactor can remain outside mitochondria when its carrier fails.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient lymphoblasts","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":"8222383b-a67b-535e-82ce-d931b6999dbf","evidence_kind":"source_excerpt","locator":"Lines 431-443","start_line":431,"end_line":443,"excerpt":"### b1-slc25a19-human-pool-separation\nG177A patient lymphoblasts had approximately tenfold lower mitochondrial ThDP despite modestly increased cytosolic ThDP.\nCondition category: machinery_impairment\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: B1 cofactor can remain outside mitochondria when its carrier fails.\norganism: Homo sapiens\ntissue_or_cell_type: Patient lymphoblasts\nexperimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.\nlimitations: Cultured lymphoblast fractions; not a plasma threshold.\nevidence_locator: Table 1\nevidence_spans: [{\"source_document\": \"artifacts/thiamine_transport_sources/PMC1595310.txt\", \"start_char\": 14675, \"end_char\": 15382}]\nevidence-scope: Patient lymphoblasts\n[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103","model_system":"Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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