{"id":"1ba563d3-5f6c-52ba-aa3d-f8a642cbfe23","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:plod2-impairment-crosslinks","predicate":"impairment_alters","statement":"Pathogenic PLOD2 variants were associated with telopeptide underhydroxylation and abnormal bone collagen cross-links.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e3124ee1-a90b-5531-bdbc-96b534d2fb80","mechanism_event_label":"An impaired enzyme can change collagen cross-links without a shortage of dietary lysine.","subject":{"id":"e7ea826f-6609-5b8a-887c-0609970a06fe","slug":"plod2","display_name":"PLOD2","entity_type_key":"protein"},"object":{"id":"47001681-1a64-5d27-9043-2ab6ba17ab3c","slug":"collagen-crosslink-pattern","display_name":"Collagen cross-link pattern","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e3124ee1-a90b-5531-bdbc-96b534d2fb80","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:plod2-impairment-crosslinks-event","event_type":"biochemical_relationship","label":"An impaired enzyme can change collagen cross-links without a shortage of dietary lysine.","description":"Pathogenic PLOD2 variants were associated with telopeptide underhydroxylation and abnormal bone collagen cross-links.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e7ea826f-6609-5b8a-887c-0609970a06fe","slug":"plod2","display_name":"PLOD2","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"47001681-1a64-5d27-9043-2ab6ba17ab3c","slug":"collagen-crosslink-pattern","display_name":"Collagen cross-link pattern","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e5d1090a-c611-5bf4-8853-b20872be5589","slug":"collagen-telopeptide-lysine","display_name":"Collagen telopeptide lysine residues","entity_type_key":"protein_state"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6921f2ab-5efc-5e56-8ba1-39af114afbf8","slug":"collagen-telopeptide-hydroxylysine","display_name":"Collagen telopeptide hydroxylysine residues","entity_type_key":"protein_state"},"role":"product","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":"experimental_model","value_text":"Bone collagen from a patient with compound-heterozygous PLOD2 variants.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rare genetic disease; cannot be generalized to low lysine intake or used as evidence that lysine treats Bruck syndrome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An impaired enzyme can change collagen cross-links without a shortage of dietary lysine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Bone","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":"f053efb7-0b75-5650-b22d-86ac26ae9986","evidence_kind":"source_excerpt","locator":"Lines 507-515","start_line":507,"end_line":515,"excerpt":"### plod2-impairment-crosslinks\nPathogenic PLOD2 variants were associated with telopeptide underhydroxylation and abnormal bone collagen cross-links.\nPlain language: An impaired enzyme can change collagen cross-links without a shortage of dietary lysine.\nCondition category: machinery_impairment\norganism: Human\ntissue_or_cell_type: Bone\nexperimental_model: Bone collagen from a patient with compound-heterozygous PLOD2 variants.\nlimitations: Rare genetic disease; cannot be generalized to low lysine intake or used as evidence that lysine treats Bruck syndrome.\n[plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/","model_system":"Bone collagen from a patient with compound-heterozygous PLOD2 variants.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact quote from the accompanying curation document, not from publisher text. Original study references: [plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/","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}