{"gene":"PF3D7_1030200","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2023,"finding":"CLAMP forms a complex with two other microneme proteins, SPATR and CLIP (CLAMP-linked invasion protein), in Toxoplasma gondii; knockdown of CLAMP does not affect parasite adhesion or microneme protein secretion but abolishes rhoptry discharge, placing CLAMP upstream of rhoptry exocytosis.","method":"Conditional knockdown, rhoptry discharge assay, co-immunoprecipitation/complex identification","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complex membership established by Co-IP and functional epistasis via conditional knockdown with specific phenotypic readout, but primary experiments in Toxoplasma; Plasmodium falciparum SPATR essentiality noted but CLAMP complex not biochemically reconstituted in Plasmodium","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"CLAMP is essential for gliding motility, salivary gland invasion, cell traversal, and productive hepatocyte invasion by Plasmodium berghei sporozoites; CLAMP-deficient sporozoites show reduced shedding of the adhesin TRAP; expansion microscopy revealed partial colocalization of CLAMP and TRAP in a subset of micronemes and distinct accumulation of CLAMP at the apical tip of sporozoites.","method":"Conditional gene deletion (dimerisable Cre recombinase), gliding motility assay, cell traversal assay, hepatocyte invasion assay, expansion microscopy","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional knockout with multiple orthogonal functional readouts (motility, traversal, invasion, TRAP shedding) plus direct localization by expansion microscopy, all in same study","pmids":["36928686"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"CLAMP is required for erythrocyte invasion by Plasmodium berghei merozoites; conditional deletion of clamp in blood stages confirmed its essential role in invasion of erythrocytes.","method":"Conditional gene deletion (DiCre/CRISPR-Cas9 dual system), erythrocyte invasion assay","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockout with defined invasion phenotype in blood stages, single lab replicating prior findings with a new genetic tool","pmids":["39849074"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"CLAMP participates in a conserved CLAMP-CLIP-SPATR microneme protein complex in Plasmodium; CLIP-deficient P. berghei sporozoites phenocopy CLAMP-deficient parasites (impaired salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility), supporting a conserved functional complex across apicomplexan invasive stages.","method":"Conditional gene deletion (DiCre/CRISPR), comparative phenotypic analysis, gliding motility assay, invasion and cell traversal assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — preprint; functional epistasis via genetic deletion with multiple phenotypic readouts in P. berghei, complex membership inferred by phenocopy and prior Toxoplasma biochemistry","pmids":["41929181"],"is_preprint":true,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"CLAMP (PF3D7_1030200) is a microneme protein that localizes to a subset of micronemes and the apical tip of invasive stages, where it forms a conserved complex with SPATR and CLIP; this complex is essential for rhoptry discharge following host-cell contact, gliding motility, and invasion across multiple Plasmodium life-cycle stages (merozoites, sporozoites), acting upstream of host cell invasion and regulating adhesin (TRAP) secretion or function."},"narrative":{"mechanistic_narrative":"CLAMP (PF3D7_1030200) is a microneme protein that functions at the apical tip of invasive apicomplexan stages to enable host-cell invasion across the Plasmodium life cycle [PMID:36928686, PMID:39849074]. It is an essential component of a conserved microneme complex with SPATR and CLIP; in Toxoplasma gondii this complex acts upstream of rhoptry exocytosis, as CLAMP knockdown abolishes rhoptry discharge without affecting parasite adhesion or microneme protein secretion [PMID:37886905]. In Plasmodium berghei sporozoites CLAMP is required for gliding motility, salivary gland invasion, cell traversal, and productive hepatocyte invasion, and its loss reduces shedding of the adhesin TRAP; expansion microscopy places CLAMP in a subset of micronemes partially overlapping TRAP and accumulating distinctly at the apical tip [PMID:36928686]. CLAMP is likewise essential for erythrocyte invasion by P. berghei merozoites [PMID:39849074], and the CLAMP partner CLIP phenocopies CLAMP loss in sporozoites, supporting a conserved CLAMP-CLIP-SPATR functional complex across invasive stages [PMID:41929181]. The precise biochemical mechanism by which CLAMP links microneme function to rhoptry discharge in Plasmodium has not been reconstituted in the available corpus.","teleology":[{"year":2023,"claim":"Established that CLAMP is not an adhesin or secretory factor per se but an upstream regulator of rhoptry discharge, defining its position in the invasion cascade.","evidence":"Conditional knockdown with rhoptry discharge assay and Co-IP defining a CLAMP-SPATR-CLIP complex in Toxoplasma gondii","pmids":["37886905"],"confidence":"Medium","gaps":["Primary functional experiments performed in Toxoplasma, not Plasmodium","CLAMP-SPATR-CLIP complex not biochemically reconstituted in Plasmodium","Molecular mechanism coupling CLAMP to rhoptry exocytosis unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Demonstrated CLAMP is essential across multiple sporozoite functions and localized it to a microneme subset and the apical tip, linking it to adhesin TRAP handling.","evidence":"Conditional gene deletion (dimerisable Cre), gliding/traversal/invasion assays, TRAP shedding analysis, and expansion microscopy in Plasmodium berghei sporozoites","pmids":["36928686"],"confidence":"High","gaps":["Whether reduced TRAP shedding is a direct or downstream consequence of CLAMP loss is unresolved","Structural basis of CLAMP apical localization not defined","Direct role in rhoptry discharge not tested in sporozoites"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Extended CLAMP essentiality to the blood stage, showing its invasion role is conserved across life-cycle stages.","evidence":"Conditional gene deletion (DiCre/CRISPR-Cas9 dual system) and erythrocyte invasion assay in Plasmodium berghei merozoites","pmids":["39849074"],"confidence":"Medium","gaps":["Mechanistic step blocked during erythrocyte invasion not defined","Complex membership in merozoites not directly tested","Single-lab replication with a new genetic tool"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"claim":"Provided genetic evidence for a conserved CLAMP-CLIP-SPATR complex by showing CLIP deletion phenocopies CLAMP loss in sporozoites.","evidence":"Conditional gene deletion (DiCre/CRISPR) with comparative gliding, invasion, and traversal assays in Plasmodium berghei (preprint)","pmids":["41929181"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Complex membership inferred by phenocopy rather than direct Plasmodium biochemistry","Stoichiometry and assembly of the complex not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How CLAMP mechanistically couples its microneme/apical localization to rhoptry discharge and adhesin function in Plasmodium remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical reconstitution of the CLAMP-SPATR-CLIP complex in Plasmodium","Molecular basis of CLAMP's regulation of rhoptry exocytosis unknown","No structural model of CLAMP or its interactions"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CLAMP-SPATR-CLIP microneme protein complex"],"partners":["SPATR","CLIP (CLAMP-LINKED INVASION PROTEIN)","TRAP (PARTIAL MICRONEME COLOCALIZATION; SHEDDING REDUCED UPON CLAMP LOSS)"],"other_free_text":["CLAMP knockdown in Toxoplasma abolishes rhoptry discharge without affecting adhesion or microneme secretion, placing it upstream of rhoptry exocytosis [#0].","CLAMP is essential for gliding motility, cell traversal, salivary gland invasion, and hepatocyte invasion by P. berghei sporozoites, and for erythrocyte invasion by merozoites [#1, #2].","CLIP deletion phenocopies CLAMP loss in sporozoites, supporting a conserved functional complex [#3].","Beyond membership in the CLAMP-SPATR-CLIP complex and genetic essentiality for invasion, the biochemical activity of CLAMP itself has not been characterized in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"37886905","id":"PMC_37886905","title":"A conserved complex of microneme proteins mediates rhoptry discharge in Toxoplasma.","date":"2023","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/37886905","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLAMP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"36928686","id":"PMC_36928686","title":"The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/36928686","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLAMP","claudin-like apicomplexan microneme protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39849074","id":"PMC_39849074","title":"Constitutive expression of Cas9 and rapamycin-inducible Cre recombinase facilitates conditional genome editing in Plasmodium berghei.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39849074","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLAMP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41929181","id":"PMC_41929181","title":"The CLAMP-Linked Invasion Protein (CLIP) plays an essential role in Plasmodium berghei zoites.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41929181","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLAMP","claudin-like apicomplexan microneme protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5139,"output_tokens":1213,"usd":0.016806,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6137,"output_tokens":2445,"usd":0.045905,"stage2_stop_reason":"end_turn"},"total_usd":0.062711,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"CLAMP forms a complex with two other microneme proteins, SPATR and CLIP (CLAMP-linked invasion protein), in Toxoplasma gondii; knockdown of CLAMP does not affect parasite adhesion or microneme protein secretion but abolishes rhoptry discharge, placing CLAMP upstream of rhoptry exocytosis.\",\n      \"method\": \"Conditional knockdown, rhoptry discharge assay, co-immunoprecipitation/complex identification\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complex membership established by Co-IP and functional epistasis via conditional knockdown with specific phenotypic readout, but primary experiments in Toxoplasma; Plasmodium falciparum SPATR essentiality noted but CLAMP complex not biochemically reconstituted in Plasmodium\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CLAMP is essential for gliding motility, salivary gland invasion, cell traversal, and productive hepatocyte invasion by Plasmodium berghei sporozoites; CLAMP-deficient sporozoites show reduced shedding of the adhesin TRAP; expansion microscopy revealed partial colocalization of CLAMP and TRAP in a subset of micronemes and distinct accumulation of CLAMP at the apical tip of sporozoites.\",\n      \"method\": \"Conditional gene deletion (dimerisable Cre recombinase), gliding motility assay, cell traversal assay, hepatocyte invasion assay, expansion microscopy\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional knockout with multiple orthogonal functional readouts (motility, traversal, invasion, TRAP shedding) plus direct localization by expansion microscopy, all in same study\",\n      \"pmids\": [\"36928686\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CLAMP is required for erythrocyte invasion by Plasmodium berghei merozoites; conditional deletion of clamp in blood stages confirmed its essential role in invasion of erythrocytes.\",\n      \"method\": \"Conditional gene deletion (DiCre/CRISPR-Cas9 dual system), erythrocyte invasion assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockout with defined invasion phenotype in blood stages, single lab replicating prior findings with a new genetic tool\",\n      \"pmids\": [\"39849074\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CLAMP participates in a conserved CLAMP-CLIP-SPATR microneme protein complex in Plasmodium; CLIP-deficient P. berghei sporozoites phenocopy CLAMP-deficient parasites (impaired salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility), supporting a conserved functional complex across apicomplexan invasive stages.\",\n      \"method\": \"Conditional gene deletion (DiCre/CRISPR), comparative phenotypic analysis, gliding motility assay, invasion and cell traversal assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — preprint; functional epistasis via genetic deletion with multiple phenotypic readouts in P. berghei, complex membership inferred by phenocopy and prior Toxoplasma biochemistry\",\n      \"pmids\": [\"41929181\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CLAMP (PF3D7_1030200) is a microneme protein that localizes to a subset of micronemes and the apical tip of invasive stages, where it forms a conserved complex with SPATR and CLIP; this complex is essential for rhoptry discharge following host-cell contact, gliding motility, and invasion across multiple Plasmodium life-cycle stages (merozoites, sporozoites), acting upstream of host cell invasion and regulating adhesin (TRAP) secretion or function.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CLAMP (PF3D7_1030200) is a microneme protein that functions at the apical tip of invasive apicomplexan stages to enable host-cell invasion across the Plasmodium life cycle [#1, #2]. It is an essential component of a conserved microneme complex with SPATR and CLIP; in Toxoplasma gondii this complex acts upstream of rhoptry exocytosis, as CLAMP knockdown abolishes rhoptry discharge without affecting parasite adhesion or microneme protein secretion [#0]. In Plasmodium berghei sporozoites CLAMP is required for gliding motility, salivary gland invasion, cell traversal, and productive hepatocyte invasion, and its loss reduces shedding of the adhesin TRAP; expansion microscopy places CLAMP in a subset of micronemes partially overlapping TRAP and accumulating distinctly at the apical tip [#1]. CLAMP is likewise essential for erythrocyte invasion by P. berghei merozoites [#2], and the CLAMP partner CLIP phenocopies CLAMP loss in sporozoites, supporting a conserved CLAMP-CLIP-SPATR functional complex across invasive stages [#3]. The precise biochemical mechanism by which CLAMP links microneme function to rhoptry discharge in Plasmodium has not been reconstituted in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Established that CLAMP is not an adhesin or secretory factor per se but an upstream regulator of rhoptry discharge, defining its position in the invasion cascade.\",\n      \"evidence\": \"Conditional knockdown with rhoptry discharge assay and Co-IP defining a CLAMP-SPATR-CLIP complex in Toxoplasma gondii\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Primary functional experiments performed in Toxoplasma, not Plasmodium\", \"CLAMP-SPATR-CLIP complex not biochemically reconstituted in Plasmodium\", \"Molecular mechanism coupling CLAMP to rhoptry exocytosis unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrated CLAMP is essential across multiple sporozoite functions and localized it to a microneme subset and the apical tip, linking it to adhesin TRAP handling.\",\n      \"evidence\": \"Conditional gene deletion (dimerisable Cre), gliding/traversal/invasion assays, TRAP shedding analysis, and expansion microscopy in Plasmodium berghei sporozoites\",\n      \"pmids\": [\"36928686\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether reduced TRAP shedding is a direct or downstream consequence of CLAMP loss is unresolved\", \"Structural basis of CLAMP apical localization not defined\", \"Direct role in rhoptry discharge not tested in sporozoites\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended CLAMP essentiality to the blood stage, showing its invasion role is conserved across life-cycle stages.\",\n      \"evidence\": \"Conditional gene deletion (DiCre/CRISPR-Cas9 dual system) and erythrocyte invasion assay in Plasmodium berghei merozoites\",\n      \"pmids\": [\"39849074\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic step blocked during erythrocyte invasion not defined\", \"Complex membership in merozoites not directly tested\", \"Single-lab replication with a new genetic tool\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Provided genetic evidence for a conserved CLAMP-CLIP-SPATR complex by showing CLIP deletion phenocopies CLAMP loss in sporozoites.\",\n      \"evidence\": \"Conditional gene deletion (DiCre/CRISPR) with comparative gliding, invasion, and traversal assays in Plasmodium berghei (preprint)\",\n      \"pmids\": [\"41929181\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Complex membership inferred by phenocopy rather than direct Plasmodium biochemistry\", \"Stoichiometry and assembly of the complex not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CLAMP mechanistically couples its microneme/apical localization to rhoptry discharge and adhesin function in Plasmodium remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical reconstitution of the CLAMP-SPATR-CLIP complex in Plasmodium\", \"Molecular basis of CLAMP's regulation of rhoptry exocytosis unknown\", \"No structural model of CLAMP or its interactions\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0120064\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0071702\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"CLAMP-SPATR-CLIP microneme protein complex\"\n    ],\n    \"partners\": [\n      \"SPATR\",\n      \"CLIP (CLAMP-linked invasion protein)\",\n      \"TRAP (partial microneme colocalization; shedding reduced upon CLAMP loss)\"\n    ],\n    \"other_free_text\": [\n      \"CLAMP knockdown in Toxoplasma abolishes rhoptry discharge without affecting adhesion or microneme secretion, placing it upstream of rhoptry exocytosis [#0].\",\n      \"CLAMP is essential for gliding motility, cell traversal, salivary gland invasion, and hepatocyte invasion by P. berghei sporozoites, and for erythrocyte invasion by merozoites [#1, #2].\",\n      \"CLIP deletion phenocopies CLAMP loss in sporozoites, supporting a conserved functional complex [#3].\",\n      \"Beyond membership in the CLAMP-SPATR-CLIP complex and genetic essentiality for invasion, the biochemical activity of CLAMP itself has not been characterized in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1030200","name":null,"product":"claudin-like apicomplexan microneme protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0514200","name":null,"product":"claudin-like apicomplexan microneme protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0614900","name":null,"product":"claudin-like apicomplexan microneme protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CLAMP","evaluation":null}