{"id":"f463c793-a17e-5a73-8890-ccfc19e5c2ff","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-asmt-n17k","predicate":"reduces","statement":"The N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e78c201f-9768-5117-a9bc-8811e5767869","mechanism_event_label":"More precursor does not automatically repair an altered enzyme.","subject":{"id":"82c096c9-e46c-5341-8cd2-06e0e7240d8f","slug":"asmt-n17k","display_name":"Human ASMT p.Asn17Lys / N17K variant","entity_type_key":"protein_state"},"object":{"id":"e1273759-0612-5d36-8a0b-cbb5e04c5f07","slug":"human-asmt-catalytic-activity","display_name":"Human ASMT catalytic activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e78c201f-9768-5117-a9bc-8811e5767869","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-asmt-n17k-event","event_type":"biochemical_relationship","label":"More precursor does not automatically repair an altered enzyme.","description":"The N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"role":"pathway_product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"82c096c9-e46c-5341-8cd2-06e0e7240d8f","slug":"asmt-n17k","display_name":"Human ASMT p.Asn17Lys / N17K variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e1273759-0612-5d36-8a0b-cbb5e04c5f07","slug":"human-asmt-catalytic-activity","display_name":"Human ASMT catalytic activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/22775292.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349\", \"start_char\": 0, \"end_char\": 1205, \"text_sha256\": \"6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"X-ray structure and radioenzymatic variant characterization","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SAM-dependent methyltransferase structure and enzyme activity assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Melatonin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human ASMT and 20 nonsynonymous variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More precursor does not automatically repair an altered enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Final melatonin synthesis step","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":"cb0214e8-5242-59c9-a966-0e89daa40ad2","evidence_kind":"source_excerpt","locator":"Lines 227-238","start_line":227,"end_line":238,"excerpt":"### melatonin-asmt-n17k\nThe N17K ASMT variant was among variants with reduced or abolished activity in the radioenzymatic screen.\nCondition category: machinery_impairment\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More precursor does not automatically repair an altered enzyme.\norganism: Human ASMT and 20 nonsynonymous variants\ntissue_or_cell_type: Final melatonin synthesis step\nexperimental_model: X-ray structure and radioenzymatic variant characterization\nlimitations: Reduced recombinant enzyme activity does not quantify pineal secretion or diagnose a sleep problem in an individual. Variant effects differ; no single universal melatonin-deficiency syndrome.\nexposure: SAM-dependent methyltransferase structure and enzyme activity assays\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/22775292.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349\", \"start_char\": 0, \"end_char\": 1205, \"text_sha256\": \"6896e0a7e08f764e1ff8c370601b0477c594e4e1c945df52d0f564e9049a9349\"}\n[melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x","model_system":"X-ray structure and radioenzymatic variant characterization","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [melatonin-p22775292] Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. (2013). https://pubmed.ncbi.nlm.nih.gov/22775292/ DOI: 10.1111/j.1600-079x.2012.01020.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"bab588de-d217-5038-9c8b-b41222eba08b","stable_key":"import-3279ff78-2460-5064-bfc0-3f2987af85a0","title":"Melatonin: synthesis, receptors, circadian timing 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. Not publisher full text.","file_path":"","sha256":"ff4f279d263f95a69da8e7e8a6c6318ab6ba1b55254dbbda1bfa9ce437e1db80","revision_id":"0318eef8-ff38-513e-8ffa-458146ca5e77","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}