{"id":"1bc18788-2ab9-511a-a41f-b32cff918f94","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-znt2-h54r-export","predicate":"reduces","statement":"Human ZnT2 H54R expressed in HEK293 cells accumulated in perinuclear aggresomal structures and showed reduced zinc secretion.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"66d164cc-e372-5c49-83f5-1a4dc9a611a2","mechanism_event_label":"A milk-zinc-associated ZnT2 variant was misplaced inside cells and exported less zinc.","subject":{"id":"8a4003c4-10fd-5113-ba8e-26fc273d4f3b","slug":"slc30a2-h54r","display_name":"Human ZnT2 H54R","entity_type_key":"protein_state"},"object":{"id":"515129c8-6c3c-5090-9b50-1b38d5d192fd","slug":"cellular-zinc-secretion","display_name":"Cellular zinc secretion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"66d164cc-e372-5c49-83f5-1a4dc9a611a2","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-znt2-h54r-export-event","event_type":"biochemical_relationship","label":"A milk-zinc-associated ZnT2 variant was misplaced inside cells and exported less zinc.","description":"Human ZnT2 H54R expressed in HEK293 cells accumulated in perinuclear aggresomal structures and showed reduced zinc secretion.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a527043c-0551-5ad5-8e90-033a73b8723a","slug":"slc30a2","display_name":"Human ZnT2 (SLC30A2)","entity_type_key":"protein"},"role":"wild_type_comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"secreted_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8a4003c4-10fd-5113-ba8e-26fc273d4f3b","slug":"slc30a2-h54r","display_name":"Human ZnT2 H54R","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"515129c8-6c3c-5090-9b50-1b38d5d192fd","slug":"cellular-zinc-secretion","display_name":"Cellular zinc secretion","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":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"H54R expression and localization assays in HEK293 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"H54R compared with wild-type ZnT2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cultured kidney-derived cells do not reproduce all lactating mammary processes; a specific variant cannot represent all maternal low-zinc milk.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A milk-zinc-associated ZnT2 variant was misplaced inside cells and exported less zinc.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293 cells; variant identified in mothers with low milk zinc","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":"8e10364c-dc3d-5b73-a9bc-2e9f0a4f2ff9","evidence_kind":"source_excerpt","locator":"Lines 310-321","start_line":310,"end_line":321,"excerpt":"### zinc-trans-znt2-h54r-export\nHuman ZnT2 H54R expressed in HEK293 cells accumulated in perinuclear aggresomal structures and showed reduced zinc secretion.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A milk-zinc-associated ZnT2 variant was misplaced inside cells and exported less zinc.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293 cells; variant identified in mothers with low milk zinc\nexperimental_model: H54R expression and localization assays in HEK293 cells\nlimitations: Cultured kidney-derived cells do not reproduce all lactating mammary processes; a specific variant cannot represent all maternal low-zinc milk.\nexposure: H54R compared with wild-type ZnT2.\ncross_nutrient: false\n[zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200","model_system":"H54R expression and localization assays in HEK293 cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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