{"gene":"PF3D7_0209100","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2019,"finding":"PATPL1 (PF3D7_0209100) possesses phospholipase A2 (PLA2) activity, as demonstrated biochemically, consistent with its patatin-like phospholipase domain.","method":"Biochemical PLA2 activity assay reported in the study","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic activity established in a single study without mutagenesis of the catalytic residues reported in the abstract","pmids":["31413195"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Conditional deletion of PATPL1 (PF3D7_0209100) does not affect P. falciparum asexual blood stage growth or gametocyte development, but reduces the efficiency of gametocyte rounding up, egress, and male gamete exflagellation following activation.","method":"Conditional gene deletion (DiCre) with phenotypic assays for rounding up, egress, and exflagellation","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional KO with multiple orthogonal phenotypic readouts (rounding up, egress, exflagellation) in a single rigorous study","pmids":["31413195"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Deletion of PATPL1 (PF3D7_0209100) inhibits secretion of the perforin-like protein PfPLP2, thereby reducing the efficiency of gamete egress, placing PATPL1 upstream of PfPLP2 in the gametogenesis pathway.","method":"Conditional gene deletion (DiCre) combined with assay of PfPLP2 secretion/localization","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis established by conditional KO with direct measurement of PfPLP2 secretion, single lab but multiple orthogonal readouts","pmids":["31413195"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Deletion of PATPL1 (PF3D7_0209100) reduces oocyst formation in Anopheles mosquitoes, demonstrating a role for PATPL1 in malaria transmission beyond gametogenesis.","method":"Conditional gene deletion (DiCre) followed by mosquito infection assay and oocyst counting","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with a well-defined in vivo transmission readout, single lab","pmids":["31413195"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"PATPL1 (PF3D7_0209100) localizes to the cytoplasm in asexual and sexual blood stage parasites.","method":"Fluorescence microscopy / subcellular localization of tagged protein in blood stages","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single localization experiment reported in a single study without functional consequence directly linked to localization","pmids":["31734953"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Gene disruption or conditional knockdown of PATPL1 (PF3D7_0209100) had no effect on intraerythrocytic growth, gametocyte development, or gametogenesis, but parasites lacking PATPL1 were impaired in gametocyte induction; conversely, PATPL1 overexpression promotes gametocyte formation.","method":"Gene disruption and conditional knockdown combined with gametocyte induction assays; overexpression with quantification of gametocyte conversion","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss-of-function and gain-of-function with defined phenotypic readout (gametocyte induction), single lab; contradicts Singh et al. 2019 regarding gametogenesis","pmids":["31734953"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Lipidomics of PATPL1 (PF3D7_0209100)-deficient asexual blood stage parasites revealed overall increased levels of major phospholipids including phosphatidylcholine (PC), consistent with a PLA2 role in PC degradation; elevated PC was proposed to suppress the signal driving gametocyte commitment.","method":"Lipidomic profiling of PATPL1-knockdown parasites","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — lipidomic measurement in conditional KD parasites, single lab, single method; mechanistic link to AP2-G/gametocytogenesis remains a hypothesis","pmids":["31734953"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Loss of PATPL1 (PF3D7_0209100) leads to transcriptional downregulation of genes related to gametocytogenesis, including the sexual commitment regulator AP2-G.","method":"Quantitative RT-PCR / transcriptional analysis of PATPL1-deficient parasites","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — transcriptional downstream effect measured by gene expression in KD parasites, single lab, single method","pmids":["31734953"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PATPL1 (PF3D7_0209100) is a cytoplasmic patatin-like phospholipase with PLA2 activity that is dispensable for asexual blood stage growth but plays a key role in P. falciparum gametogenesis: it acts upstream of the perforin-like protein PfPLP2 to facilitate its secretion, and its loss impairs gametocyte rounding up, egress, exflagellation, and oocyst formation in mosquitoes; a separate study also implicates PATPL1 in gametocyte induction through regulation of phosphatidylcholine levels and AP2-G transcription, though the two studies report contradictory findings regarding which stage of sexual development is primarily affected."},"narrative":{"mechanistic_narrative":"PATPL1 (PF3D7_0209100) is a cytoplasmic patatin-like phospholipase that governs sexual-stage progression and transmission of Plasmodium falciparum [PMID:31413195, PMID:31734953]. It possesses phospholipase A2 (PLA2) activity in vitro, consistent with its patatin-like domain [PMID:31413195]. PATPL1 is dispensable for asexual intraerythrocytic growth, but its conditional deletion reduces the efficiency of gametocyte rounding up, egress, and male gamete exflagellation, and diminishes oocyst formation in Anopheles mosquitoes [PMID:31413195]. Mechanistically, PATPL1 acts upstream of the perforin-like protein PfPLP2, and its loss impairs PfPLP2 secretion, linking its phospholipase activity to the egress machinery [PMID:31413195]. A separate study instead implicates PATPL1 in gametocyte induction: its loss impairs sexual commitment while overexpression promotes gametocyte formation, correlated with elevated phosphatidylcholine and other phospholipids (consistent with a PLA2 role in phospholipid degradation) and with transcriptional downregulation of the sexual commitment regulator AP2-G [PMID:31734953]. The two studies report contradictory conclusions about which stage of sexual development PATPL1 primarily controls.","teleology":[{"year":2019,"claim":"Establishing that PATPL1 is an enzymatically active phospholipase converted a domain-based annotation into a biochemically defined PLA2 activity.","evidence":"In vitro PLA2 activity assay of PATPL1 in P. falciparum","pmids":["31413195"],"confidence":"Medium","gaps":["Catalytic residues not mutated to confirm the activity derives from the patatin domain","In vivo substrate specificity not defined","Activity assayed in a single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Conditional deletion defined which stages depend on PATPL1, showing it is dispensable for asexual growth but required for efficient gametocyte rounding up, egress, and exflagellation.","evidence":"DiCre conditional gene deletion with phenotypic assays for rounding up, egress, and exflagellation in P. falciparum","pmids":["31413195"],"confidence":"High","gaps":["Molecular trigger linking PLA2 activity to the rounding-up/egress program not resolved","Whether phospholipase activity is required for the phenotype not tested by catalytic-dead complementation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Placing PATPL1 upstream of PfPLP2 secretion provided a mechanistic route by which its loss impairs gamete egress.","evidence":"DiCre conditional deletion combined with assay of PfPLP2 secretion/localization in P. falciparum","pmids":["31413195"],"confidence":"High","gaps":["Whether PATPL1 acts directly on the PfPLP2 secretory pathway or indirectly via membrane lipid remodeling is unknown","No physical interaction between PATPL1 and PfPLP2 demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Mosquito infection experiments extended PATPL1's role from gametogenesis to transmission by showing reduced oocyst formation upon deletion.","evidence":"DiCre conditional deletion followed by Anopheles infection and oocyst counting","pmids":["31413195"],"confidence":"High","gaps":["Whether the oocyst defect is fully attributable to the upstream exflagellation/egress defect not separated","No ookinete-stage analysis"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Localization of tagged PATPL1 to the cytoplasm situated the phospholipase in a soluble compartment during both asexual and sexual blood stages.","evidence":"Fluorescence microscopy of tagged PATPL1 in blood-stage P. falciparum","pmids":["31734953"],"confidence":"Medium","gaps":["No functional consequence directly tied to the observed localization","Dynamic relocalization during gametogenesis not examined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"A second study assigned PATPL1 a role in gametocyte induction via loss- and gain-of-function, and proposed a lipid-signaling mechanism, directly conflicting with the gametogenesis-stage model.","evidence":"Gene disruption/knockdown, overexpression with gametocyte induction assays, lipidomics, and transcriptional analysis of AP2-G in P. falciparum","pmids":["31734953"],"confidence":"Medium","gaps":["Contradicts the finding that PATPL1 is required at gametogenesis rather than commitment (idx 1)","Causal link from elevated phosphatidylcholine to AP2-G suppression remains a hypothesis","Single lab, single method for the lipidomic and transcriptional readouts"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unresolved whether PATPL1 primarily controls gametocyte commitment (via phospholipid/AP2-G signaling) or gametogenesis (via PfPLP2 secretion), and whether its catalytic PLA2 activity is required for either.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No catalytic-dead complementation to test whether phenotypes depend on PLA2 activity","The two published models make contradictory stage assignments and have not been reconciled","No structural model or in vivo substrate identification"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPLP2 (PERFORIN-LIKE PROTEIN 2; PATPL1 ACTS UPSTREAM OF ITS SECRETION) [#2]"],"other_free_text":["PATPL1 loss elevates major phospholipids including phosphatidylcholine, consistent with a PLA2 role in phospholipid degradation [#6]","PATPL1 loss downregulates gametocytogenesis genes including the sexual commitment regulator AP2-G [#7]","Two studies disagree on whether PATPL1 acts at gametocyte induction/commitment [#5, #6, #7] or at gametogenesis/egress [#1, #2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"31413195","id":"PMC_31413195","title":"Role of a patatin-like phospholipase in Plasmodium falciparum gametogenesis and malaria transmission.","date":"2019","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/31413195","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31734953","id":"PMC_31734953","title":"A patatin-like phospholipase functions during gametocyte induction in the malaria parasite Plasmodium falciparum.","date":"2019","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31734953","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41662857","id":"","title":"Parasite clearance in patients with Plasmodium vivax monoinfection treated with artesunate in Cambodia: an observational secondary analysis of trial data.","date":"2026","source":"The Lancet. Microbe","url":"https://pubmed.ncbi.nlm.nih.gov/41662857","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37352369","id":"","title":"A malaria parasite phospholipase facilitates efficient asexual blood stage egress.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37352369","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38089812","id":"","title":"The patatin-like phospholipase PfPNPLA2 is involved in the mitochondrial degradation of phosphatidylglycerol during Plasmodium falciparum blood stage development.","date":"2023","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38089812","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34845210","id":"","title":"Molecular interactions between parasite and mosquito during midgut invasion as targets to block malaria transmission.","date":"2021","source":"NPJ vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/34845210","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35638735","id":"","title":"PfARID Regulates P. falciparum Malaria Parasite Male Gametogenesis and Female Fertility and Is Critical for Parasite Transmission to the Mosquito Vector.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35638735","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33886685","id":"","title":"Some conditions apply: Systems for studying Plasmodium falciparum protein function.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33886685","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PATPL1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9869,"output_tokens":2027,"usd":0.030006,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7240,"output_tokens":2779,"usd":0.052838,"stage2_stop_reason":"end_turn"},"total_usd":0.082844,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"PATPL1 (PF3D7_0209100) possesses phospholipase A2 (PLA2) activity, as demonstrated biochemically, consistent with its patatin-like phospholipase domain.\",\n      \"method\": \"Biochemical PLA2 activity assay reported in the study\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic activity established in a single study without mutagenesis of the catalytic residues reported in the abstract\",\n      \"pmids\": [\"31413195\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Conditional deletion of PATPL1 (PF3D7_0209100) does not affect P. falciparum asexual blood stage growth or gametocyte development, but reduces the efficiency of gametocyte rounding up, egress, and male gamete exflagellation following activation.\",\n      \"method\": \"Conditional gene deletion (DiCre) with phenotypic assays for rounding up, egress, and exflagellation\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with multiple orthogonal phenotypic readouts (rounding up, egress, exflagellation) in a single rigorous study\",\n      \"pmids\": [\"31413195\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Deletion of PATPL1 (PF3D7_0209100) inhibits secretion of the perforin-like protein PfPLP2, thereby reducing the efficiency of gamete egress, placing PATPL1 upstream of PfPLP2 in the gametogenesis pathway.\",\n      \"method\": \"Conditional gene deletion (DiCre) combined with assay of PfPLP2 secretion/localization\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis established by conditional KO with direct measurement of PfPLP2 secretion, single lab but multiple orthogonal readouts\",\n      \"pmids\": [\"31413195\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Deletion of PATPL1 (PF3D7_0209100) reduces oocyst formation in Anopheles mosquitoes, demonstrating a role for PATPL1 in malaria transmission beyond gametogenesis.\",\n      \"method\": \"Conditional gene deletion (DiCre) followed by mosquito infection assay and oocyst counting\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with a well-defined in vivo transmission readout, single lab\",\n      \"pmids\": [\"31413195\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PATPL1 (PF3D7_0209100) localizes to the cytoplasm in asexual and sexual blood stage parasites.\",\n      \"method\": \"Fluorescence microscopy / subcellular localization of tagged protein in blood stages\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization experiment reported in a single study without functional consequence directly linked to localization\",\n      \"pmids\": [\"31734953\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Gene disruption or conditional knockdown of PATPL1 (PF3D7_0209100) had no effect on intraerythrocytic growth, gametocyte development, or gametogenesis, but parasites lacking PATPL1 were impaired in gametocyte induction; conversely, PATPL1 overexpression promotes gametocyte formation.\",\n      \"method\": \"Gene disruption and conditional knockdown combined with gametocyte induction assays; overexpression with quantification of gametocyte conversion\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss-of-function and gain-of-function with defined phenotypic readout (gametocyte induction), single lab; contradicts Singh et al. 2019 regarding gametogenesis\",\n      \"pmids\": [\"31734953\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Lipidomics of PATPL1 (PF3D7_0209100)-deficient asexual blood stage parasites revealed overall increased levels of major phospholipids including phosphatidylcholine (PC), consistent with a PLA2 role in PC degradation; elevated PC was proposed to suppress the signal driving gametocyte commitment.\",\n      \"method\": \"Lipidomic profiling of PATPL1-knockdown parasites\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — lipidomic measurement in conditional KD parasites, single lab, single method; mechanistic link to AP2-G/gametocytogenesis remains a hypothesis\",\n      \"pmids\": [\"31734953\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Loss of PATPL1 (PF3D7_0209100) leads to transcriptional downregulation of genes related to gametocytogenesis, including the sexual commitment regulator AP2-G.\",\n      \"method\": \"Quantitative RT-PCR / transcriptional analysis of PATPL1-deficient parasites\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — transcriptional downstream effect measured by gene expression in KD parasites, single lab, single method\",\n      \"pmids\": [\"31734953\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PATPL1 (PF3D7_0209100) is a cytoplasmic patatin-like phospholipase with PLA2 activity that is dispensable for asexual blood stage growth but plays a key role in P. falciparum gametogenesis: it acts upstream of the perforin-like protein PfPLP2 to facilitate its secretion, and its loss impairs gametocyte rounding up, egress, exflagellation, and oocyst formation in mosquitoes; a separate study also implicates PATPL1 in gametocyte induction through regulation of phosphatidylcholine levels and AP2-G transcription, though the two studies report contradictory findings regarding which stage of sexual development is primarily affected.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PATPL1 (PF3D7_0209100) is a cytoplasmic patatin-like phospholipase that governs sexual-stage progression and transmission of Plasmodium falciparum [#1, #4, #5]. It possesses phospholipase A2 (PLA2) activity in vitro, consistent with its patatin-like domain [#0]. PATPL1 is dispensable for asexual intraerythrocytic growth, but its conditional deletion reduces the efficiency of gametocyte rounding up, egress, and male gamete exflagellation, and diminishes oocyst formation in Anopheles mosquitoes [#1, #3]. Mechanistically, PATPL1 acts upstream of the perforin-like protein PfPLP2, and its loss impairs PfPLP2 secretion, linking its phospholipase activity to the egress machinery [#2]. A separate study instead implicates PATPL1 in gametocyte induction: its loss impairs sexual commitment while overexpression promotes gametocyte formation, correlated with elevated phosphatidylcholine and other phospholipids (consistent with a PLA2 role in phospholipid degradation) and with transcriptional downregulation of the sexual commitment regulator AP2-G [#5, #6, #7]. The two studies report contradictory conclusions about which stage of sexual development PATPL1 primarily controls.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing that PATPL1 is an enzymatically active phospholipase converted a domain-based annotation into a biochemically defined PLA2 activity.\",\n      \"evidence\": \"In vitro PLA2 activity assay of PATPL1 in P. falciparum\",\n      \"pmids\": [\"31413195\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Catalytic residues not mutated to confirm the activity derives from the patatin domain\",\n        \"In vivo substrate specificity not defined\",\n        \"Activity assayed in a single study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Conditional deletion defined which stages depend on PATPL1, showing it is dispensable for asexual growth but required for efficient gametocyte rounding up, egress, and exflagellation.\",\n      \"evidence\": \"DiCre conditional gene deletion with phenotypic assays for rounding up, egress, and exflagellation in P. falciparum\",\n      \"pmids\": [\"31413195\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular trigger linking PLA2 activity to the rounding-up/egress program not resolved\",\n        \"Whether phospholipase activity is required for the phenotype not tested by catalytic-dead complementation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placing PATPL1 upstream of PfPLP2 secretion provided a mechanistic route by which its loss impairs gamete egress.\",\n      \"evidence\": \"DiCre conditional deletion combined with assay of PfPLP2 secretion/localization in P. falciparum\",\n      \"pmids\": [\"31413195\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PATPL1 acts directly on the PfPLP2 secretory pathway or indirectly via membrane lipid remodeling is unknown\",\n        \"No physical interaction between PATPL1 and PfPLP2 demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Mosquito infection experiments extended PATPL1's role from gametogenesis to transmission by showing reduced oocyst formation upon deletion.\",\n      \"evidence\": \"DiCre conditional deletion followed by Anopheles infection and oocyst counting\",\n      \"pmids\": [\"31413195\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the oocyst defect is fully attributable to the upstream exflagellation/egress defect not separated\",\n        \"No ookinete-stage analysis\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Localization of tagged PATPL1 to the cytoplasm situated the phospholipase in a soluble compartment during both asexual and sexual blood stages.\",\n      \"evidence\": \"Fluorescence microscopy of tagged PATPL1 in blood-stage P. falciparum\",\n      \"pmids\": [\"31734953\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional consequence directly tied to the observed localization\",\n        \"Dynamic relocalization during gametogenesis not examined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"A second study assigned PATPL1 a role in gametocyte induction via loss- and gain-of-function, and proposed a lipid-signaling mechanism, directly conflicting with the gametogenesis-stage model.\",\n      \"evidence\": \"Gene disruption/knockdown, overexpression with gametocyte induction assays, lipidomics, and transcriptional analysis of AP2-G in P. falciparum\",\n      \"pmids\": [\"31734953\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Contradicts the finding that PATPL1 is required at gametogenesis rather than commitment (idx 1)\",\n        \"Causal link from elevated phosphatidylcholine to AP2-G suppression remains a hypothesis\",\n        \"Single lab, single method for the lipidomic and transcriptional readouts\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved whether PATPL1 primarily controls gametocyte commitment (via phospholipid/AP2-G signaling) or gametogenesis (via PfPLP2 secretion), and whether its catalytic PLA2 activity is required for either.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No catalytic-dead complementation to test whether phenotypes depend on PLA2 activity\",\n        \"The two published models make contradictory stage assignments and have not been reconciled\",\n        \"No structural model or in vivo substrate identification\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004623\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016042\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0060468\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0007320\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfPLP2 (perforin-like protein 2; PATPL1 acts upstream of its secretion) [#2]\"\n    ],\n    \"other_free_text\": [\n      \"PATPL1 loss elevates major phospholipids including phosphatidylcholine, consistent with a PLA2 role in phospholipid degradation [#6]\",\n      \"PATPL1 loss downregulates gametocytogenesis genes including the sexual commitment regulator AP2-G [#7]\",\n      \"Two studies disagree on whether PATPL1 acts at gametocyte induction/commitment [#5, #6, #7] or at gametogenesis/egress [#1, #2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0209100","name":null,"product":"patatin-like phospholipase 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0306200","name":null,"product":"patatin-like phospholipase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0412000","name":null,"product":"patatin-like phospholipase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PATPL1","evaluation":null}