{"id":"9d8f2e57-760d-545f-a5e5-ae446334c067","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-hgd-variants","predicate":"when_defective_impairs","statement":"Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3c078c13-cc3a-52e4-9d94-275c05722be4","mechanism_event_label":"How enzyme subunits fit together can affect metabolic disposal.","subject":{"id":"60587707-1969-5d03-a3ba-d03912c5dc40","slug":"hgd","display_name":"Human homogentisate 1,2-dioxygenase / HGD","entity_type_key":"protein"},"object":{"id":"d6a8cb78-4767-544b-8f13-1723c1bd7e0d","slug":"human-hgd-catabolic-function","display_name":"Human HGD-dependent homogentisate catabolism","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3c078c13-cc3a-52e4-9d94-275c05722be4","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-hgd-variants-event","event_type":"observed_relationship","label":"How enzyme subunits fit together can affect metabolic disposal.","description":"Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"60587707-1969-5d03-a3ba-d03912c5dc40","slug":"hgd","display_name":"Human homogentisate 1,2-dioxygenase / HGD","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d6a8cb78-4767-544b-8f13-1723c1bd7e0d","slug":"human-hgd-catabolic-function","display_name":"Human HGD-dependent homogentisate catabolism","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bcfef85f-831d-5439-ba51-1aef4b090441","slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ea7ed42c-7c9f-5d5a-912a-7b67e60df93e","slug":"homogentisate","display_name":"Homogentisate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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unverified.","entity":null}],"evidence":[{"id":"ed4c739e-56b9-5e43-9430-729399850df8","evidence_kind":"source_excerpt","locator":"Lines 244-250","start_line":244,"end_line":250,"excerpt":"## l-tyrosine-hgd-variants\nHow enzyme subunits fit together can affect metabolic disposal.\nAlkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure.\nModel: Mapping disease-associated variants onto a human hexameric structure.\nLimitations: Structural mapping is not a functional assay for every variant or a universal severity predictor.\nEvidence access: Primary abstract\nCrystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756","model_system":"Mapping disease-associated variants onto a human hexameric structure.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"12917df2-c6e0-5b61-850f-dbff6d4b4d30","stable_key":"import-63ce713e-6aea-59f6-9896-ca30e010b2ce","title":"L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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