{"id":"3c189e97-55f8-53b2-96be-a210ae116d5b","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-trans-r94x-biotin","predicate":"fails_to_induce","statement":"Expression of human SLC5A6 R94X failed to induce biotin uptake above control in HuTu-80 and U87 cells, whereas wild-type SLC5A6 increased uptake.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"43be661f-cdd5-5c31-9393-30c82d08626f","mechanism_event_label":"The R94X SMVT variant lost the uptake activity seen with the normal transporter.","subject":{"id":"8b3fd223-1d69-580e-8a82-c64deca26217","slug":"slc5a6-r94x","display_name":"Human SLC5A6 R94X truncated protein","entity_type_key":"protein_state"},"object":{"id":"d25f4daa-5529-568f-b319-7c30e444914b","slug":"cellular-biotin-uptake","display_name":"Cellular biotin uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"43be661f-cdd5-5c31-9393-30c82d08626f","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-trans-r94x-biotin-event","event_type":"biochemical_relationship","label":"The R94X SMVT variant lost the uptake activity seen with the normal transporter.","description":"Expression of human SLC5A6 R94X failed to induce biotin uptake above control in HuTu-80 and U87 cells, whereas wild-type SLC5A6 increased uptake.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3bd59e38-e6b1-5223-b4de-faa33835f5bc","slug":"slc5a6","display_name":"Human sodium-dependent multivitamin transporter / SLC5A6","entity_type_key":"protein"},"role":"wild_type_comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"measured_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7bc62072-9517-5563-a3b8-8c5ab64a464b","slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"},"role":"shared_machinery_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8b3fd223-1d69-580e-8a82-c64deca26217","slug":"slc5a6-r94x","display_name":"Human SLC5A6 R94X truncated protein","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d25f4daa-5529-568f-b319-7c30e444914b","slug":"cellular-biotin-uptake","display_name":"Cellular biotin uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Forty-eight hours after transfection; 5 nM [3H]biotin, pH 7.4, 37 degrees C, five-minute uptake.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Human transformed cell models expressing GFP-tagged constructs. Biotin is the measured substrate; impaired B5/lipoate transport is plausible through shared machinery but is not directly quantified here. Genetic dysfunction is not dietary B5 deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The R94X SMVT variant lost the uptake activity seen with the normal transporter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HuTu-80 duodenal-derived epithelial and U87 brain-derived glioma cells","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":"b1457f91-7c41-5983-9253-0f137e91c525","evidence_kind":"source_excerpt","locator":"Lines 340-351","start_line":340,"end_line":351,"excerpt":"### b5-trans-r94x-biotin\nExpression of human SLC5A6 R94X failed to induce biotin uptake above control in HuTu-80 and U87 cells, whereas wild-type SLC5A6 increased uptake.\nCondition category: machinery_impairment\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The R94X SMVT variant lost the uptake activity seen with the normal transporter.\norganism: Homo sapiens\ntissue_or_cell_type: HuTu-80 duodenal-derived epithelial and U87 brain-derived glioma cells\nexperimental_model: Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants\nlimitations: Human transformed cell models expressing GFP-tagged constructs. Biotin is the measured substrate; impaired B5/lipoate transport is plausible through shared machinery but is not directly quantified here. Genetic dysfunction is not dietary B5 deficiency.\nexposure: Forty-eight hours after transfection; 5 nM [3H]biotin, pH 7.4, 37 degrees C, five-minute uptake.\ncross_nutrient: true\n[b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x","model_system":"Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0716b500-dd0b-5425-b9d0-d88bc9c09e86","stable_key":"import-f992b796-377d-53bf-a39b-7e5d41dbe194","title":"Pantothenic acid (vitamin B5): coenzyme A, deficiency 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":"b5a49f5a2373ca6064c9a4e014e052dad2f6f199a82bb09b26b82b831c36110b","revision_id":"78f3e793-f084-5ee2-8703-b661c4b650bf","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}