{"id":"b2bdb6fb-1f4b-5a06-b891-887c413c53cf","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-trans-patient-fibroblast-biotin","predicate":"reduces","statement":"Fibroblasts from the proband with SLC5A6 c.393+2T>C and p.Ser429Gly variants showed approximately 90% lower biotin uptake than controls.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5d628996-98ff-596d-ab8b-4b84dbdcefaf","mechanism_event_label":"A patient with two SLC5A6 variants had a large defect in cellular biotin entry.","subject":{"id":"5d469a1c-3c99-5f6b-9e45-e92fabadd043","slug":"human-slc5a6-c393-plus-2t-c-ser429gly","display_name":"Human SLC5A6 c.393+2T>C / p.Ser429Gly genotype","entity_type_key":"gene"},"object":{"id":"c90636ba-4a6d-54fc-9f3a-37bc348492f4","slug":"human-fibroblast-biotin-uptake","display_name":"Human fibroblast biotin uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5d628996-98ff-596d-ab8b-4b84dbdcefaf","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-trans-patient-fibroblast-biotin-event","event_type":"biochemical_relationship","label":"A patient with two SLC5A6 variants had a large defect in cellular biotin entry.","description":"Fibroblasts from the proband with SLC5A6 c.393+2T>C and p.Ser429Gly variants showed approximately 90% lower biotin uptake than controls.","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":"affected_transport_machinery","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":"other_shared_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5d469a1c-3c99-5f6b-9e45-e92fabadd043","slug":"human-slc5a6-c393-plus-2t-c-ser429gly","display_name":"Human SLC5A6 c.393+2T>C / p.Ser429Gly genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c90636ba-4a6d-54fc-9f3a-37bc348492f4","slug":"human-fibroblast-biotin-uptake","display_name":"Human fibroblast 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":"Patient-derived fibroblasts in a human SLC5A6 family study; molecular and radiolabeled biotin uptake analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"The p.Ser429Gly allele supplied canonically spliced transcripts in the compound-heterozygous proband; uptake compared with control fibroblasts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Abstract-only transport extraction. This is one proband genotype, not an isolated p.Ser429Gly dose-response study; neither pantothenate uptake nor the relative contribution of individual supplements is quantified.","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":"A patient with two SLC5A6 variants had a large defect in cellular biotin entry.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-trans-neuropathy2024] Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy. (2024). https://pubmed.ncbi.nlm.nih.gov/38816490/ DOI: 10.1038/s41431-024-01641-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient-derived 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":"e1ccc525-2e95-5fb8-aa1e-0134880059c9","evidence_kind":"source_excerpt","locator":"Lines 392-403","start_line":392,"end_line":403,"excerpt":"### b5-trans-patient-fibroblast-biotin\nFibroblasts from the proband with SLC5A6 c.393+2T>C and p.Ser429Gly variants showed approximately 90% lower biotin uptake than controls.\nCondition category: machinery_impairment\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A patient with two SLC5A6 variants had a large defect in cellular biotin entry.\norganism: Homo sapiens\ntissue_or_cell_type: Patient-derived fibroblasts\nexperimental_model: Patient-derived fibroblasts in a human SLC5A6 family study; molecular and radiolabeled biotin uptake analysis\nlimitations: Abstract-only transport extraction. This is one proband genotype, not an isolated p.Ser429Gly dose-response study; neither pantothenate uptake nor the relative contribution of individual supplements is quantified.\nexposure: The p.Ser429Gly allele supplied canonically spliced transcripts in the compound-heterozygous proband; uptake compared with control fibroblasts.\ncross_nutrient: true\n[b5-trans-neuropathy2024] Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy. (2024). https://pubmed.ncbi.nlm.nih.gov/38816490/ DOI: 10.1038/s41431-024-01641-8","model_system":"Patient-derived fibroblasts in a human SLC5A6 family study; molecular and radiolabeled biotin uptake analysis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-trans-neuropathy2024] Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy. (2024). https://pubmed.ncbi.nlm.nih.gov/38816490/ DOI: 10.1038/s41431-024-01641-8","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}