{"id":"fef5ac08-c1b0-5ca6-a798-83a0a71ebd38","stable_key":"649e861b-265a-5912-bc36-3a73e53ef892:l-serine-pss1-feedback","predicate":"normally_inhibits","statement":"PTDSS1 variants from Lenz-Majewski syndrome markedly reduced product inhibition by phosphatidylserine and increased phosphatidylserine synthesis in patient fibroblasts.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"be510046-2506-55c0-86ec-cf701ff49dd7","mechanism_event_label":"Failure of a feedback brake can increase lipid production.","subject":{"id":"0e2dd859-6135-556e-938f-d177f1e8c1ad","slug":"phosphatidylserine","display_name":"Phosphatidylserine","entity_type_key":"lipid"},"object":{"id":"0b5548b5-3cd8-5f19-8eea-dfae2a671fb3","slug":"ptdss1","display_name":"Human phosphatidylserine synthase 1 / PTDSS1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"be510046-2506-55c0-86ec-cf701ff49dd7","stable_key":"649e861b-265a-5912-bc36-3a73e53ef892:l-serine-pss1-feedback-event","event_type":"observed_relationship","label":"Failure of a feedback brake can increase lipid production.","description":"PTDSS1 variants from Lenz-Majewski syndrome markedly reduced product inhibition by phosphatidylserine and increased phosphatidylserine synthesis in patient fibroblasts.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0e2dd859-6135-556e-938f-d177f1e8c1ad","slug":"phosphatidylserine","display_name":"Phosphatidylserine","entity_type_key":"lipid"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0b5548b5-3cd8-5f19-8eea-dfae2a671fb3","slug":"ptdss1","display_name":"Human phosphatidylserine synthase 1 / PTDSS1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"},"role":"context_participant","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_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human genetics and patient fibroblast synthesis assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"These gain-of-function variants are not serine shortage or proof of an effect from phosphatidylserine supplements.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Failure of a feedback brake can increase lipid production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24241535/ · DOI 10.1038/ng.2829","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":"77cb2090-012e-5349-b4a9-a2b48bc0adae","evidence_kind":"source_excerpt","locator":"Lines 262-268","start_line":262,"end_line":268,"excerpt":"## l-serine-pss1-feedback\nFailure of a feedback brake can increase lipid production.\nPTDSS1 variants from Lenz-Majewski syndrome markedly reduced product inhibition by phosphatidylserine and increased phosphatidylserine synthesis in patient fibroblasts.\nModel: Human genetics and patient fibroblast synthesis assays.\nLimitations: These gain-of-function variants are not serine shortage or proof of an effect from phosphatidylserine supplements.\nEvidence access: Primary abstract\nGain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24241535/ · DOI 10.1038/ng.2829","model_system":"Human genetics and patient fibroblast synthesis assays.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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