{"id":"7d6d57ac-872d-53a7-af8a-a31bddb9df8f","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:dhtkd1-oxoadipate-accumulation","predicate":"impairment_accumulates","statement":"DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4d437787-8249-574e-9531-78d2243aee8a","mechanism_event_label":"A downstream enzyme defect leaves oxoadipate uncleared.","subject":{"id":"b8552ee2-4a84-59a0-9694-69991c9903bf","slug":"dhtkd1","display_name":"DHTKD1","entity_type_key":"protein"},"object":{"id":"22cbb32f-fa6b-57a0-a02d-8f2083585223","slug":"2-oxoadipate","display_name":"2-Oxoadipate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"4d437787-8249-574e-9531-78d2243aee8a","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:dhtkd1-oxoadipate-accumulation-event","event_type":"biochemical_relationship","label":"A downstream enzyme defect leaves oxoadipate uncleared.","description":"DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b8552ee2-4a84-59a0-9694-69991c9903bf","slug":"dhtkd1","display_name":"DHTKD1","entity_type_key":"protein"},"role":"impaired_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"22cbb32f-fa6b-57a0-a02d-8f2083585223","slug":"2-oxoadipate","display_name":"2-Oxoadipate","entity_type_key":"small_molecule"},"role":"accumulating_metabolite","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5fff6664-209e-5c35-b88e-ac15c1c5fbc0","slug":"l-lysine","display_name":"L-Lysine","entity_type_key":"small_molecule"},"role":"traced_precursor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"affected_machinery","value_text":"Oxoadipate-dehydrogenase E1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"deficiency_not_equivalent","value_text":"Dietary lysine deficiency","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two human patients and isotope-traced fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biochemical causation is stronger than attribution of every neurological finding.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A downstream enzyme defect leaves oxoadipate uncleared.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Fibroblasts; clinical aciduria","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":"73624902-491e-5111-9594-ab792654b70a","evidence_kind":"source_excerpt","locator":"Lines 278-288","start_line":278,"end_line":288,"excerpt":"### dhtkd1-oxoadipate-accumulation\nDHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.\nPlain language: A downstream enzyme defect leaves oxoadipate uncleared.\nCondition category: machinery_impairment\norganism: Homo sapiens\ntissue_or_cell_type: Fibroblasts; clinical aciduria\nexperimental_model: Two human patients and isotope-traced fibroblasts\nlimitations: Biochemical causation is stronger than attribution of every neurological finding.\naffected_machinery: Oxoadipate-dehydrogenase E1\ndeficiency_not_equivalent: Dietary lysine deficiency\n[danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006","model_system":"Two human patients and isotope-traced fibroblasts","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact quote from the accompanying curation document, not from publisher text. Original study references: [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"7633bde7-dcc9-5086-91c6-a45eb96857f3","stable_key":"import-c3df3634-4c3a-5099-a5d9-e4f6344c1084","title":"L-Lysine: mechanism-first literature curation (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":"93998d47c21525409ba82f1c82ededf2893dff15fbe61c7deffc175b0e298e97","revision_id":"3897e31f-6624-59e1-a053-8a81b7361632","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}