{"id":"45763bd7-64ef-53f7-b509-f78b7fc81b18","stable_key":"649e861b-265a-5912-bc36-3a73e53ef892:l-serine-psph-variant","predicate":"loses_activity_with","statement":"The A35T PSPH substitution reduced catalytic efficiency about fiftyfold and lowered thermal stability; M52T had milder effects and D32N behaved like wild type in these assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b7f5833d-3c2c-58bd-b926-31b9be3e74a8","mechanism_event_label":"Different variants in the same gene can have very different biochemical effects.","subject":{"id":"1177919d-d7f4-5272-b40c-444f5dbee4d2","slug":"psph","display_name":"Human phosphoserine phosphatase / PSPH","entity_type_key":"protein"},"object":{"id":"b22d8276-55c0-51f9-98ed-f828ac0b17f8","slug":"human-psph-a35t-function","display_name":"Human PSPH A35T catalytic function","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b7f5833d-3c2c-58bd-b926-31b9be3e74a8","stable_key":"649e861b-265a-5912-bc36-3a73e53ef892:l-serine-psph-variant-event","event_type":"observed_relationship","label":"Different variants in the same gene can have very different biochemical effects.","description":"The A35T PSPH substitution reduced catalytic efficiency about fiftyfold and lowered thermal stability; M52T had milder effects and D32N behaved like wild type in these assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1177919d-d7f4-5272-b40c-444f5dbee4d2","slug":"psph","display_name":"Human phosphoserine phosphatase / PSPH","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b22d8276-55c0-51f9-98ed-f828ac0b17f8","slug":"human-psph-a35t-function","display_name":"Human PSPH A35T catalytic function","entity_type_key":"cellular_process"},"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":"Recombinant human natural variants.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assay behavior does not independently resolve the clinical pathogenicity of every variant.","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":"Different variants in the same gene can have very different biochemical effects.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034","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":"3be1e0e5-e836-5b59-80ef-5839048adeda","evidence_kind":"source_excerpt","locator":"Lines 78-84","start_line":78,"end_line":84,"excerpt":"## l-serine-psph-variant\nDifferent variants in the same gene can have very different biochemical effects.\nThe A35T PSPH substitution reduced catalytic efficiency about fiftyfold and lowered thermal stability; M52T had milder effects and D32N behaved like wild type in these assays.\nModel: Recombinant human natural variants.\nLimitations: Assay behavior does not independently resolve the clinical pathogenicity of every variant.\nEvidence access: Primary abstract\nEffect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034","model_system":"Recombinant human natural variants.","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":"70bcf57a-36bb-563f-9073-2d616e5f155a","stable_key":"import-649e861b-265a-5912-bc36-3a73e53ef892","title":"L-Serine: synthesis, one-carbon metabolism, lipids 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. Not publisher full text.","file_path":"","sha256":"22a750ce2b94f8607268c58322c48c4f0468f403b72a4008307538a6e5ff86d5","revision_id":"c1d6a7e1-9558-5bc6-9e3b-7080c26d3dbc","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}