{"gene":"PF3D7_0210600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2020,"finding":"CERLI1 (PF3D7_0210600) localizes to the cytosolic face of the rhoptry bulb membrane in P. falciparum merozoites, as determined by biochemical fractionation and semi-quantitative super-resolution microscopy.","method":"Biochemical fractionation, super-resolution microscopy (localization experiment with functional context)","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization by multiple orthogonal methods (biochemical fractionation + super-resolution microscopy) in a single rigorous study with functional follow-up","pmids":["32179747"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Knockdown of CERLI1 (PF3D7_0210600) inhibits merozoite invasion of erythrocytes without disrupting schizogony or merozoite organelle biogenesis, demonstrating an essential role specifically in rhoptry function rather than organelle formation.","method":"Conditional knockdown (loss-of-function) with invasion and schizogony phenotypic readouts","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with clearly defined cellular phenotype (invasion block, normal schizogony), single lab but two orthogonal phenotypic readouts","pmids":["32179747"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Knockdown of CERLI1 (PF3D7_0210600) prevents secretion of key rhoptry antigens that coordinate merozoite invasion, as shown by biochemical assays and semi-quantitative super-resolution microscopy, establishing a direct role for CERLI1 in rhoptry exocytosis.","method":"Biochemical assays and semi-quantitative super-resolution microscopy following conditional knockdown","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with two orthogonal readouts (biochemistry + super-resolution microscopy) demonstrating rhoptry secretion block, single lab","pmids":["32179747"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"The SIP2 AP2 transcription factor in P. berghei directly targets the cerli1 gene locus (peak within 1200 bp of start codon detected by ChIP-seq), indicating that CERLI1 transcription is under control of this master regulator of merozoite formation.","method":"ChIP-seq (chromatin immunoprecipitation followed by sequencing) for PbSIP2 binding sites genome-wide","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — ChIP-seq is a direct binding assay identifying CERLI1 as a transcriptional target, but functional consequence of this specific binding on CERLI1 expression was not individually validated; single lab, single method for this gene","pmids":["40117352"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"CERLI1 (PF3D7_0210600) is a conserved protein that localizes to the cytosolic face of the rhoptry bulb membrane in P. falciparum merozoites and is essential for rhoptry exocytosis and erythrocyte invasion: its knockdown blocks secretion of key rhoptry antigens without disrupting organelle biogenesis or schizogony, and its transcription is directly activated by the SIP2 AP2 master transcription factor during schizogony in P. berghei."},"narrative":{"mechanistic_narrative":"CERLI1 (PF3D7_0210600) is a conserved protein required for erythrocyte invasion by Plasmodium falciparum merozoites, where it acts at the rhoptry to enable secretion of invasion effectors [PMID:32179747]. It localizes to the cytosolic face of the rhoptry bulb membrane [PMID:32179747], and conditional knockdown blocks merozoite invasion while leaving schizogony and merozoite organelle biogenesis intact, defining a role in rhoptry function rather than organelle formation [PMID:32179747]. Mechanistically, loss of CERLI1 prevents secretion of key rhoptry antigens that coordinate invasion, establishing it as a factor essential for rhoptry exocytosis [PMID:32179747]. In P. berghei, transcription of the cerli1 locus is directly targeted by the SIP2 AP2 transcription factor, placing CERLI1 expression under a master regulator of merozoite formation [PMID:40117352]. Beyond its rhoptry localization, invasion/secretion requirement, and transcriptional regulation, no direct molecular partners, biochemical activity, or structural detail for CERLI1 have been characterized in the available corpus.","teleology":[{"year":2020,"claim":"To place CERLI1 in the invasion machinery, its subcellular position had to be defined; localization to the cytosolic face of the rhoptry bulb membrane established it as a peripheral rhoptry-associated protein rather than a lumenal cargo.","evidence":"Biochemical fractionation and semi-quantitative super-resolution microscopy in P. falciparum merozoites","pmids":["32179747"],"confidence":"High","gaps":["How CERLI1 is anchored or recruited to the rhoptry bulb membrane is not defined","No interacting membrane or complex partners identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether CERLI1 is needed for building rhoptries or for their function was unresolved; conditional knockdown blocked invasion without perturbing schizogony or organelle biogenesis, pinpointing a functional rather than biogenetic role.","evidence":"Conditional knockdown with invasion and schizogony phenotypic readouts in P. falciparum","pmids":["32179747"],"confidence":"High","gaps":["The specific step of invasion arrested (attachment, tight junction, or entry) is not resolved","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"The mechanism behind the invasion block needed definition; knockdown was shown to prevent secretion of key rhoptry antigens, establishing CERLI1 as required for rhoptry exocytosis.","evidence":"Biochemical assays and semi-quantitative super-resolution microscopy following conditional knockdown in P. falciparum","pmids":["32179747"],"confidence":"High","gaps":["The molecular step in exocytosis CERLI1 controls (docking, priming, fusion) is unknown","No demonstrated direct binding to secretory or fusion machinery"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"How CERLI1 expression is timed to merozoite formation was unaddressed; ChIP-seq showed the SIP2 AP2 factor directly binds the cerli1 locus, linking its transcription to a master regulator of merozoite development.","evidence":"ChIP-seq of PbSIP2 binding sites genome-wide in P. berghei","pmids":["40117352"],"confidence":"Medium","gaps":["Functional consequence of SIP2 binding on CERLI1 expression was not individually validated","Shown in P. berghei; not confirmed for the P. falciparum ortholog","Single lab, single method for this gene"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct molecular partners and biochemical activity by which CERLI1 promotes rhoptry secretion remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No interacting proteins or complex membership defined for CERLI1","No enzymatic or biochemical activity characterized","No structural model available"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Localizes to the cytosolic face of the rhoptry bulb membrane in P. falciparum merozoites [#0]","Essential for merozoite invasion of erythrocytes; knockdown does not disrupt schizogony or organelle biogenesis [#1]","Required for secretion of key rhoptry antigens (rhoptry exocytosis) [#2]","cerli1 locus is a direct binding target of the SIP2 AP2 transcription factor in P. berghei [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32179747","id":"PMC_32179747","title":"PfCERLI1 is a conserved rhoptry associated protein essential for Plasmodium falciparum merozoite invasion of erythrocytes.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32179747","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfCERLI1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42556607","id":"PMC_42556607","title":"Artificial Intelligence based identification of druggability of essential hypothetical proteins in Plasmodium falciparum.","date":"2026","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/42556607","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfCERLI1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42211658","id":"","title":"Physiology of invasive Plasmodium merozoites.","date":"2026","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42211658","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CERLI1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40626728","id":"","title":"The Plasmodium falciparum homolog of Vps16 interacts with the core members of the Vps-C tethering complex.","date":"2025","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/40626728","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CERLI1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40117352","id":"","title":"SIP2 is the master transcription factor of Plasmodium merozoite formation.","date":"2025","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/40117352","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CERLI1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38529021","id":"","title":"Population genomic evidence of structured and connected Plasmodium vivax populations under host selection in Latin America.","date":"2024","source":"Ecology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/38529021","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CERLI1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8500,"output_tokens":1097,"usd":0.020977,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5927,"output_tokens":1989,"usd":0.03968,"stage2_stop_reason":"end_turn"},"total_usd":0.060657,"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\": 2020,\n      \"finding\": \"CERLI1 (PF3D7_0210600) localizes to the cytosolic face of the rhoptry bulb membrane in P. falciparum merozoites, as determined by biochemical fractionation and semi-quantitative super-resolution microscopy.\",\n      \"method\": \"Biochemical fractionation, super-resolution microscopy (localization experiment with functional context)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by multiple orthogonal methods (biochemical fractionation + super-resolution microscopy) in a single rigorous study with functional follow-up\",\n      \"pmids\": [\"32179747\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Knockdown of CERLI1 (PF3D7_0210600) inhibits merozoite invasion of erythrocytes without disrupting schizogony or merozoite organelle biogenesis, demonstrating an essential role specifically in rhoptry function rather than organelle formation.\",\n      \"method\": \"Conditional knockdown (loss-of-function) with invasion and schizogony phenotypic readouts\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with clearly defined cellular phenotype (invasion block, normal schizogony), single lab but two orthogonal phenotypic readouts\",\n      \"pmids\": [\"32179747\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Knockdown of CERLI1 (PF3D7_0210600) prevents secretion of key rhoptry antigens that coordinate merozoite invasion, as shown by biochemical assays and semi-quantitative super-resolution microscopy, establishing a direct role for CERLI1 in rhoptry exocytosis.\",\n      \"method\": \"Biochemical assays and semi-quantitative super-resolution microscopy following conditional knockdown\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with two orthogonal readouts (biochemistry + super-resolution microscopy) demonstrating rhoptry secretion block, single lab\",\n      \"pmids\": [\"32179747\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The SIP2 AP2 transcription factor in P. berghei directly targets the cerli1 gene locus (peak within 1200 bp of start codon detected by ChIP-seq), indicating that CERLI1 transcription is under control of this master regulator of merozoite formation.\",\n      \"method\": \"ChIP-seq (chromatin immunoprecipitation followed by sequencing) for PbSIP2 binding sites genome-wide\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — ChIP-seq is a direct binding assay identifying CERLI1 as a transcriptional target, but functional consequence of this specific binding on CERLI1 expression was not individually validated; single lab, single method for this gene\",\n      \"pmids\": [\"40117352\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CERLI1 (PF3D7_0210600) is a conserved protein that localizes to the cytosolic face of the rhoptry bulb membrane in P. falciparum merozoites and is essential for rhoptry exocytosis and erythrocyte invasion: its knockdown blocks secretion of key rhoptry antigens without disrupting organelle biogenesis or schizogony, and its transcription is directly activated by the SIP2 AP2 master transcription factor during schizogony in P. berghei.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CERLI1 (PF3D7_0210600) is a conserved protein required for erythrocyte invasion by Plasmodium falciparum merozoites, where it acts at the rhoptry to enable secretion of invasion effectors [#0, #2]. It localizes to the cytosolic face of the rhoptry bulb membrane [#0], and conditional knockdown blocks merozoite invasion while leaving schizogony and merozoite organelle biogenesis intact, defining a role in rhoptry function rather than organelle formation [#1]. Mechanistically, loss of CERLI1 prevents secretion of key rhoptry antigens that coordinate invasion, establishing it as a factor essential for rhoptry exocytosis [#2]. In P. berghei, transcription of the cerli1 locus is directly targeted by the SIP2 AP2 transcription factor, placing CERLI1 expression under a master regulator of merozoite formation [#3]. Beyond its rhoptry localization, invasion/secretion requirement, and transcriptional regulation, no direct molecular partners, biochemical activity, or structural detail for CERLI1 have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"To place CERLI1 in the invasion machinery, its subcellular position had to be defined; localization to the cytosolic face of the rhoptry bulb membrane established it as a peripheral rhoptry-associated protein rather than a lumenal cargo.\",\n      \"evidence\": \"Biochemical fractionation and semi-quantitative super-resolution microscopy in P. falciparum merozoites\",\n      \"pmids\": [\"32179747\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How CERLI1 is anchored or recruited to the rhoptry bulb membrane is not defined\",\n        \"No interacting membrane or complex partners identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether CERLI1 is needed for building rhoptries or for their function was unresolved; conditional knockdown blocked invasion without perturbing schizogony or organelle biogenesis, pinpointing a functional rather than biogenetic role.\",\n      \"evidence\": \"Conditional knockdown with invasion and schizogony phenotypic readouts in P. falciparum\",\n      \"pmids\": [\"32179747\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific step of invasion arrested (attachment, tight junction, or entry) is not resolved\",\n        \"Single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The mechanism behind the invasion block needed definition; knockdown was shown to prevent secretion of key rhoptry antigens, establishing CERLI1 as required for rhoptry exocytosis.\",\n      \"evidence\": \"Biochemical assays and semi-quantitative super-resolution microscopy following conditional knockdown in P. falciparum\",\n      \"pmids\": [\"32179747\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular step in exocytosis CERLI1 controls (docking, priming, fusion) is unknown\",\n        \"No demonstrated direct binding to secretory or fusion machinery\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"How CERLI1 expression is timed to merozoite formation was unaddressed; ChIP-seq showed the SIP2 AP2 factor directly binds the cerli1 locus, linking its transcription to a master regulator of merozoite development.\",\n      \"evidence\": \"ChIP-seq of PbSIP2 binding sites genome-wide in P. berghei\",\n      \"pmids\": [\"40117352\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of SIP2 binding on CERLI1 expression was not individually validated\",\n        \"Shown in P. berghei; not confirmed for the P. falciparum ortholog\",\n        \"Single lab, single method for this gene\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular partners and biochemical activity by which CERLI1 promotes rhoptry secretion remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No interacting proteins or complex membership defined for CERLI1\",\n        \"No enzymatic or biochemical activity characterized\",\n        \"No structural model available\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0033104\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Localizes to the cytosolic face of the rhoptry bulb membrane in P. falciparum merozoites [#0]\",\n      \"Essential for merozoite invasion of erythrocytes; knockdown does not disrupt schizogony or organelle biogenesis [#1]\",\n      \"Required for secretion of key rhoptry antigens (rhoptry exocytosis) [#2]\",\n      \"cerli1 locus is a direct binding target of the SIP2 AP2 transcription factor in P. berghei [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0210600","name":null,"product":"protein CERLI1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0307500","name":null,"product":"protein CERLI1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0410600","name":null,"product":"protein CERLI1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CERLI1","evaluation":null}