{"id":"c67871e8-a861-5dd8-823f-863ea7a9c6b2","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-mct8-d424n-binding-transport","predicate":"impairs","statement":"Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"fb6e5c90-7703-5504-9ed1-6e74698ae878","mechanism_event_label":"A transporter may still bind hormone while failing to deliver it into cells.","subject":{"id":"d6933481-48f0-5364-870c-5b3cf9e79c57","slug":"slc16a2-d424n-short-isoform","display_name":"Human MCT8 D424N (D498N in long isoform)","entity_type_key":"protein_state"},"object":{"id":"a146600b-de7a-56b1-9ae1-8a51e4f053b2","slug":"cellular-thyroxine-uptake","display_name":"Cellular thyroxine uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fb6e5c90-7703-5504-9ed1-6e74698ae878","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-mct8-d424n-binding-transport-event","event_type":"biochemical_relationship","label":"A transporter may still bind hormone while failing to deliver it into cells.","description":"Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d6933481-48f0-5364-870c-5b3cf9e79c57","slug":"slc16a2-d424n-short-isoform","display_name":"Human MCT8 D424N (D498N in long isoform)","entity_type_key":"protein_state"},"role":"impaired_transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"98c25617-10b5-50ab-b330-7e6b7fa595bb","slug":"slc16a2","display_name":"Human MCT8 / SLC16A2","entity_type_key":"protein"},"role":"wild_type_comparator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a146600b-de7a-56b1-9ae1-8a51e4f053b2","slug":"cellular-thyroxine-uptake","display_name":"Cellular thyroxine uptake","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_locator","value_text":"Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/40368961.txt\", \"locator\": \"Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant\", \"start_char\": 16912, \"end_char\": 18212}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Patient-derived D424N short isoform, equivalent to D498N long isoform; wild-type comparator.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The proposed conformational explanation is structural interpretation; no dietary intervention.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A transporter may still bind hormone while failing to deliver it into cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified mutant and HeLa 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":"f16a3a0e-1668-5f29-a514-41dddc1195fc","evidence_kind":"source_excerpt","locator":"Lines 940-952","start_line":940,"end_line":952,"excerpt":"### i-met-mct8-d424n-binding-transport\nHuman MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence.\nCondition category: machinery_impairment\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A transporter may still bind hormone while failing to deliver it into cells.\norganism: Human\ntissue_or_cell_type: Purified mutant and HeLa cells\nexperimental_model: Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays\nlimitations: The proposed conformational explanation is structural interpretation; no dietary intervention.\nexposure: Patient-derived D424N short isoform, equivalent to D498N long isoform; wild-type comparator.\nevidence_locator: Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/40368961.txt\", \"locator\": \"Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant\", \"start_char\": 16912, \"end_char\": 18212}]\n[i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. 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