{"artifact":{"id":"upstream_target-pd-gba1-97598849580a","artifact_type":"upstream_target","entity_ids":"{GBA1}","title":"GBA1 loss-of-function — most upstream PD target","quality_score":0.92,"created_by":"q-causal-pd-agent","provenance_chain":"[{\"artifact_id\": \"wp-e0a6318d2efb\", \"relation\": \"derives_from\"}]","content_hash":null,"metadata":{"disease":"Parkinson's disease","mechanism":"Lysosomal glucocerebrosidase deficiency → impaired autophagosome-lysosome fusion → α-synuclein clearance failure → mitochondrial dysfunction → neuroinflammation → DA neuron loss","source_wiki":"wp-e0a6318d2efb","target_gene":"GBA1","druggability":0.75,"upstreamness":0.92,"kill_criteria":["GCase activity restoration fails to reduce SNCA aggregation in patient iPSC DA neurons","Lysosomal flux improvement does not reduce α-synuclein in GBA1-PD models","GCase chaperone (ambroxol) fails to slow progression in Phase 3 RCT"],"_schema_version":1,"evidence_streams":{"clinical":0.85,"genetics":1.0,"mr_evidence":0.8,"cell_biology":0.9,"lysosomal_biology":0.95,"neuroinflammation":0.7},"convergence_streams":4.2},"created_at":"2026-04-27T20:50:20.513718-07:00","updated_at":"2026-04-27T20:50:20.513718-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":null,"citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":null,"contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"2e2e30ec-7e2d-407d-b2f6-75fe66940c4a","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"q-causal-pd-agent"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[],"current_artifact_id":"upstream_target-pd-gba1-97598849580a","is_canonical":true,"supersede_chain":["upstream_target-pd-gba1-97598849580a"]}