{"gene":"PF3D7_1249600","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2006,"finding":"LRR12 (PfLRR1, PF3D7_1249600) physically interacts with PfPP1 (protein phosphatase type 1) as demonstrated by GST pull-down assay, and the LRR12–PfPP1 complex was confirmed in parasite extracts by co-immunoprecipitation; LRR12 inhibits PfPP1 phosphatase activity in vitro.","method":"GST pull-down assay, co-immunoprecipitation from parasite extracts, in vitro phosphatase activity assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal pull-down plus in vitro activity assay in a single lab, two orthogonal methods","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"LRR12 (PfLRR1) expressed in Xenopus oocytes interacted with endogenous Xenopus PP1 and promoted progression through the G2/M cell cycle checkpoint, inducing germinal vesicle breakdown (GVBD), consistent with PP1 inhibition overcoming the checkpoint.","method":"Xenopus oocyte functional assay (GVBD readout), comparison with anti-PP1 antibody and okadaic acid controls","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — heterologous functional assay with pharmacological controls, single lab","pmids":["16629662"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"LRR12 (PfLRR1) transcript is highly expressed in late intraerythrocytic stages (late trophozoites and schizonts), as determined by real-time quantitative PCR of cDNA cloned from P. falciparum.","method":"Real-time quantitative PCR, cDNA cloning and sequencing","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional expression data only, single lab, single method; no functional consequence demonstrated","pmids":["17689674"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"LRR12 (PF3D7_1249600) physically binds and inhibits the protein phosphatase PfPP1 in P. falciparum, and its orthologue in P. berghei (PbLRR1) similarly forms a complex with PbPP1, downregulates its phosphatase activity, and is required for efficient oocyst development in mosquitoes; in a heterologous Xenopus system, LRR12 promotes G2/M cell cycle progression by suppressing PP1 activity."},"narrative":{"mechanistic_narrative":"LRR12 (PfLRR1, PF3D7_1249600) is a leucine-rich repeat protein of Plasmodium falciparum that functions as a regulator of the protein phosphatase PfPP1: it physically binds PfPP1 in vitro and in parasite extracts and inhibits PfPP1 phosphatase activity [PMID:16629662]. Consistent with this inhibitory role, expression of LRR12 in Xenopus oocytes engages endogenous PP1 and drives progression through the G2/M checkpoint, inducing germinal vesicle breakdown as expected for relief of PP1 activity [PMID:16629662]. Its transcript accumulates in late intraerythrocytic stages (late trophozoites and schizonts) [PMID:17689674]. Beyond its role as a PfPP1-binding inhibitor and this stage-specific expression, no further mechanistic detail for PF3D7_1249600 has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Establishing whether LRR12 acts on the PfPP1 phosphatase answered whether this LRR protein is a bona fide phosphatase regulator rather than an uncharacterized structural protein.","evidence":"GST pull-down and co-immunoprecipitation from parasite extracts plus in vitro phosphatase assay in P. falciparum","pmids":["16629662"],"confidence":"Medium","gaps":["The domain of LRR12 mediating PfPP1 binding was not mapped","Whether the interaction is regulated during the parasite life cycle was not addressed","No structural model of the LRR12–PfPP1 complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Testing LRR12 in a heterologous cell-cycle system answered whether its PfPP1 inhibition has a functional cellular consequence, showing it can override a G2/M checkpoint.","evidence":"Xenopus oocyte GVBD functional assay with anti-PP1 antibody and okadaic acid controls","pmids":["16629662"],"confidence":"Medium","gaps":["Activity shown only in a heterologous Xenopus system, not in the parasite","The physiological cell-cycle role of LRR12 in P. falciparum was not demonstrated","No genetic loss-of-function in the parasite"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Profiling LRR12 transcript timing answered when in the intraerythrocytic cycle it is expressed, placing peak abundance in late trophozoites and schizonts.","evidence":"Real-time quantitative PCR of cloned cDNA from P. falciparum","pmids":["17689674"],"confidence":"Low","gaps":["Transcript data only; protein-level expression not confirmed","No functional consequence tied to the stage-specific expression","Single method, single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether LRR12 is essential for P. falciparum intraerythrocytic development and how PfPP1 inhibition by LRR12 is regulated in the parasite remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No parasite genetic knockout or conditional knockdown of PF3D7_1249600","PfPP1 substrates dephosphorylated in an LRR12-dependent manner are unidentified","No structural basis for the inhibitory interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["LRR12–PfPP1 complex"],"partners":["PFPP1 (PROTEIN PHOSPHATASE TYPE 1)"],"other_free_text":["LRR12 transcript peaks in late trophozoites and schizonts of the intraerythrocytic cycle [#2]","In Xenopus oocytes LRR12 binds endogenous PP1 and induces GVBD, consistent with PP1 inhibition [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16629662","id":"PMC_16629662","title":"Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine-rich repeat protein of the human malaria parasite Plasmodium falciparum.","date":"2006","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16629662","citation_count":34,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17689674","id":"PMC_17689674","title":"Census, molecular characterization and developmental expression of Leucine-Rich-Repeat proteins in Plasmodium falciparum.","date":"2007","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/17689674","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35920043","id":"PMC_35920043","title":"Plasmodium berghei leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development.","date":"2022","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/35920043","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42294623","id":"PMC_42294623","title":"Plasmodium falciparum leucine-rich repeat 5 disruption alters the transcription progression during asexual and sexual stage development.","date":"2026","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/42294623","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["leucine-rich repeat protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5028,"output_tokens":880,"usd":0.014142,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5550,"output_tokens":1719,"usd":0.035362,"stage2_stop_reason":"end_turn"},"total_usd":0.049504,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"LRR12 (PfLRR1, PF3D7_1249600) physically interacts with PfPP1 (protein phosphatase type 1) as demonstrated by GST pull-down assay, and the LRR12–PfPP1 complex was confirmed in parasite extracts by co-immunoprecipitation; LRR12 inhibits PfPP1 phosphatase activity in vitro.\",\n      \"method\": \"GST pull-down assay, co-immunoprecipitation from parasite extracts, in vitro phosphatase activity assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pull-down plus in vitro activity assay in a single lab, two orthogonal methods\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"LRR12 (PfLRR1) expressed in Xenopus oocytes interacted with endogenous Xenopus PP1 and promoted progression through the G2/M cell cycle checkpoint, inducing germinal vesicle breakdown (GVBD), consistent with PP1 inhibition overcoming the checkpoint.\",\n      \"method\": \"Xenopus oocyte functional assay (GVBD readout), comparison with anti-PP1 antibody and okadaic acid controls\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — heterologous functional assay with pharmacological controls, single lab\",\n      \"pmids\": [\"16629662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"LRR12 (PfLRR1) transcript is highly expressed in late intraerythrocytic stages (late trophozoites and schizonts), as determined by real-time quantitative PCR of cDNA cloned from P. falciparum.\",\n      \"method\": \"Real-time quantitative PCR, cDNA cloning and sequencing\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional expression data only, single lab, single method; no functional consequence demonstrated\",\n      \"pmids\": [\"17689674\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"LRR12 (PF3D7_1249600) physically binds and inhibits the protein phosphatase PfPP1 in P. falciparum, and its orthologue in P. berghei (PbLRR1) similarly forms a complex with PbPP1, downregulates its phosphatase activity, and is required for efficient oocyst development in mosquitoes; in a heterologous Xenopus system, LRR12 promotes G2/M cell cycle progression by suppressing PP1 activity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LRR12 (PfLRR1, PF3D7_1249600) is a leucine-rich repeat protein of Plasmodium falciparum that functions as a regulator of the protein phosphatase PfPP1: it physically binds PfPP1 in vitro and in parasite extracts and inhibits PfPP1 phosphatase activity [#0]. Consistent with this inhibitory role, expression of LRR12 in Xenopus oocytes engages endogenous PP1 and drives progression through the G2/M checkpoint, inducing germinal vesicle breakdown as expected for relief of PP1 activity [#1]. Its transcript accumulates in late intraerythrocytic stages (late trophozoites and schizonts) [#2]. Beyond its role as a PfPP1-binding inhibitor and this stage-specific expression, no further mechanistic detail for PF3D7_1249600 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing whether LRR12 acts on the PfPP1 phosphatase answered whether this LRR protein is a bona fide phosphatase regulator rather than an uncharacterized structural protein.\",\n      \"evidence\": \"GST pull-down and co-immunoprecipitation from parasite extracts plus in vitro phosphatase assay in P. falciparum\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The domain of LRR12 mediating PfPP1 binding was not mapped\",\n        \"Whether the interaction is regulated during the parasite life cycle was not addressed\",\n        \"No structural model of the LRR12–PfPP1 complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Testing LRR12 in a heterologous cell-cycle system answered whether its PfPP1 inhibition has a functional cellular consequence, showing it can override a G2/M checkpoint.\",\n      \"evidence\": \"Xenopus oocyte GVBD functional assay with anti-PP1 antibody and okadaic acid controls\",\n      \"pmids\": [\"16629662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Activity shown only in a heterologous Xenopus system, not in the parasite\",\n        \"The physiological cell-cycle role of LRR12 in P. falciparum was not demonstrated\",\n        \"No genetic loss-of-function in the parasite\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Profiling LRR12 transcript timing answered when in the intraerythrocytic cycle it is expressed, placing peak abundance in late trophozoites and schizonts.\",\n      \"evidence\": \"Real-time quantitative PCR of cloned cDNA from P. falciparum\",\n      \"pmids\": [\"17689674\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcript data only; protein-level expression not confirmed\",\n        \"No functional consequence tied to the stage-specific expression\",\n        \"Single method, single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether LRR12 is essential for P. falciparum intraerythrocytic development and how PfPP1 inhibition by LRR12 is regulated in the parasite remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No parasite genetic knockout or conditional knockdown of PF3D7_1249600\",\n        \"PfPP1 substrates dephosphorylated in an LRR12-dependent manner are unidentified\",\n        \"No structural basis for the inhibitory interaction\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004865\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000086\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"LRR12–PfPP1 complex\"\n    ],\n    \"partners\": [\n      \"PfPP1 (protein phosphatase type 1)\"\n    ],\n    \"other_free_text\": [\n      \"LRR12 transcript peaks in late trophozoites and schizonts of the intraerythrocytic cycle [#2]\",\n      \"In Xenopus oocytes LRR12 binds endogenous PP1 and induces GVBD, consistent with PP1 inhibition [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1249600","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 cited papers name other catalogue genes (PF3D7_1032800, PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1249600","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1462500","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1469300","name":null,"product":"leucine-rich repeat protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"LRR12","evaluation":null}