{"id":"0069d3a0-bec4-5848-9c78-58d76a6befec","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-pycr2-genetic","predicate":"when_defective_disrupts","statement":"PYCR2 variants in two families were associated with microcephaly and hypomyelination; engineered PYCR2 loss in HEK293FT cells lowered mitochondrial membrane potential and increased oxidative-stress-induced apoptosis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"569f4c6e-0ec4-5bec-a845-b4a131a5fbb4","mechanism_event_label":"A related enzyme has a distinct neurological disease pattern.","subject":{"id":"1efec84e-42f6-51db-9041-6b35fc092e3d","slug":"pycr2","display_name":"Human pyrroline-5-carboxylate reductase 2 / PYCR2","entity_type_key":"protein"},"object":{"id":"1f35f7f3-9bb7-57f7-a31b-d522ccf5ae7d","slug":"human-pycr2-mitochondrial-stress-response","display_name":"Mitochondrial stress response in PYCR2-deficient human cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"569f4c6e-0ec4-5bec-a845-b4a131a5fbb4","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-pycr2-genetic-event","event_type":"observed_relationship","label":"A related enzyme has a distinct neurological disease pattern.","description":"PYCR2 variants in two families were associated with microcephaly and hypomyelination; engineered PYCR2 loss in HEK293FT cells lowered mitochondrial membrane potential and increased oxidative-stress-induced apoptosis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1efec84e-42f6-51db-9041-6b35fc092e3d","slug":"pycr2","display_name":"Human pyrroline-5-carboxylate reductase 2 / PYCR2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1f35f7f3-9bb7-57f7-a31b-d522ccf5ae7d","slug":"human-pycr2-mitochondrial-stress-response","display_name":"Mitochondrial stress response in PYCR2-deficient human cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","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 families, variant-expression studies and CRISPR-modified human cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This does not prove that low circulating proline is the disease mechanism or that extra substrate rescues it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A related enzyme has a distinct neurological disease pattern.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865492/ · DOI 10.1016/j.ajhg.2015.03.003","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":"a96e5937-6691-5335-ba56-92e750a20ba1","evidence_kind":"source_excerpt","locator":"Lines 158-164","start_line":158,"end_line":164,"excerpt":"## l-proline-pycr2-genetic\nA related enzyme has a distinct neurological disease pattern.\nPYCR2 variants in two families were associated with microcephaly and hypomyelination; engineered PYCR2 loss in HEK293FT cells lowered mitochondrial membrane potential and increased oxidative-stress-induced apoptosis.\nModel: Human families, variant-expression studies and CRISPR-modified human cells.\nLimitations: This does not prove that low circulating proline is the disease mechanism or that extra substrate rescues it.\nEvidence access: Primary abstract\nMutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25865492/ · DOI 10.1016/j.ajhg.2015.03.003","model_system":"Human families, variant-expression studies and CRISPR-modified human cells.","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":"e5aa7fc5-ee52-5376-8169-416082a89fd1","stable_key":"import-6612c190-1948-5bcf-bbe3-a7f6c50fa3cf","title":"L-Proline: synthesis, collagen processing, redox metabolism 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":"7b7f1981f9c7897fbb6baa19425bdc19dede78ad4d66fa554394b8337c7366fb","revision_id":"4971a925-fa70-59f8-8030-d3029a18a62f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}