{"gene":"PF3D7_1367200","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2023,"finding":"CLAMP (PF3D7_1367200) is essential for Plasmodium falciparum asexual blood stage growth; conventional gene deletion is refractory, indicating an essential role in erythrocyte invasion.","method":"Conditional genome editing (dimerisable Cre recombinase) in P. berghei; gene deletion and functional analysis","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined invasion phenotype, replicated across two independent studies (PMID:36928686 and PMID:39849074)","pmids":["36928686","39849074"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"CLAMP is essential for gliding motility and invasion of mosquito salivary glands and mammalian hepatocytes by P. berghei sporozoites; CLAMP-deficient sporozoites show reduced shedding of the sporozoite adhesin TRAP.","method":"Conditional gene deletion (DiCre) in P. berghei transmission stages; gliding motility assays, cell traversal assays, productive invasion assays, expansion microscopy for colocalization with TRAP","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with multiple orthogonal phenotypic readouts (motility, cell traversal, invasion) and colocalization evidence in a single rigorous study","pmids":["36928686"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"CLAMP partially colocalizes with the adhesin TRAP in a subset of micronemes and accumulates distinctly at the apical tip of P. berghei sporozoites, placing it upstream of host cell invasion.","method":"Expansion microscopy and colocalization analysis in P. berghei sporozoites","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single microscopy method; localization tied functionally to TRAP shedding defect but without direct biochemical validation","pmids":["36928686"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"CLAMP forms a conserved microneme protein complex with SPATR and CLIP (CLAMP-Linked Invasion Protein) in Toxoplasma gondii; phylogenetic analysis indicates that CLAMP and CLIP orthologs are ubiquitous across apicomplexans, and SPATR is also essential for P. falciparum blood-stage invasion.","method":"Complex identification (biochemical/genetic analysis in T. gondii); phylogenetic analysis; knockdown of each complex member showing rhoptry discharge defect","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complex membership established in T. gondii with functional validation; P. falciparum CLAMP essentiality inferred from prior blood-stage data; single lab for Plasmodium-specific portion","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Conditional deletion of clamp in P. berghei blood stages (using a dual CRISPR/Cas9 + DiCre parasite line) confirmed the essential role of CLAMP during erythrocyte invasion by merozoites.","method":"Conditional KO using constitutive Cas9 + rapamycin-inducible DiCre in P. berghei; growth and invasion assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined invasion phenotype; single lab, confirmatory study","pmids":["39849074"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"CLIP (the CLAMP-linked invasion protein) and CLAMP form a conserved complex in P. berghei; deletion of clip phenocopies deletion of clamp, causing defects in erythrocyte invasion by merozoites, salivary gland invasion by sporozoites, cell traversal, hepatocyte invasion, and gliding motility, supporting a conserved CLAMP-CLIP-SPATR complex essential across invasive stages.","method":"CRISPR-assisted conditional gene deletion (DiCre) of clip in P. berghei blood and transmission stages; growth assays, gliding motility assays, cell traversal, invasion assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with multiple orthogonal phenotypic readouts; preprint, single lab, not yet peer-reviewed","pmids":["41929181"],"is_preprint":true,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1367200 (CLAMP) is a conserved microneme protein essential for host cell invasion across multiple Plasmodium life-cycle stages (merozoites, sporozoites), where it functions upstream of host-cell contact—likely regulating rhoptry discharge and adhesin (TRAP) secretion/shedding—as part of a conserved complex with CLIP and SPATR; its apical tip localization in sporozoites and the phenotypic recapitulation by CLIP deletion support a shared CLAMP-CLIP-SPATR complex mechanism for invasion."},"narrative":{"mechanistic_narrative":"PF3D7_1367200 (CLAMP) is a conserved microneme protein essential for host-cell invasion across multiple Plasmodium life-cycle stages [PMID:36928686, PMID:39849074]. In P. falciparum and P. berghei, CLAMP is required for asexual blood-stage growth, with conventional deletion refractory and conditional deletion establishing an essential role in erythrocyte invasion by merozoites [PMID:36928686, PMID:39849074]. In P. berghei transmission stages, CLAMP is additionally required for sporozoite gliding motility, cell traversal, and invasion of mosquito salivary glands and mammalian hepatocytes, positioning it upstream of productive host-cell entry [PMID:36928686]. CLAMP-deficient sporozoites show reduced shedding of the adhesin TRAP, and CLAMP partially colocalizes with TRAP in a subset of micronemes while accumulating distinctly at the apical tip [PMID:36928686]. In Toxoplasma gondii, CLAMP forms a conserved microneme complex with SPATR and CLIP, and both CLAMP and CLIP orthologs are distributed across apicomplexans; deletion of clip in P. berghei phenocopies clamp deletion across all invasive stages, supporting a shared CLAMP-CLIP-SPATR complex mechanism for invasion [PMID:37886905, PMID:41929181]. Beyond its essentiality, its complex membership, and its correlation with TRAP shedding, the direct biochemical mechanism by which PF3D7_1367200 CLAMP regulates invasion has not been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Whether CLAMP has an essential role in Plasmodium was unknown; conditional deletion established that it is required for asexual blood-stage growth and erythrocyte invasion.","evidence":"Conditional genome editing (DiCre) in P. berghei with refractory conventional deletion in P. falciparum; growth and invasion analysis","pmids":["36928686","39849074"],"confidence":"High","gaps":["The molecular activity of CLAMP during invasion was not defined","Whether the invasion defect is due to failed attachment, rhoptry discharge, or motility was not resolved at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"It was unclear whether CLAMP function extended beyond blood stages; conditional deletion in transmission stages showed it is required for sporozoite gliding, traversal, and invasion, generalizing its role to multiple invasive stages.","evidence":"Conditional gene deletion (DiCre) in P. berghei transmission stages with gliding motility, cell traversal, and productive invasion assays","pmids":["36928686"],"confidence":"High","gaps":["The step at which motility/invasion fails was not mechanistically dissected","Whether reduced TRAP shedding is causal or a downstream consequence was not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"The subcellular basis for CLAMP's invasion role was unknown; expansion microscopy placed CLAMP at the sporozoite apical tip and in a subset of TRAP-containing micronemes, tying it to adhesin secretion.","evidence":"Expansion microscopy and colocalization with TRAP in P. berghei sporozoites","pmids":["36928686"],"confidence":"Medium","gaps":["Localization rests on a single microscopy method without direct biochemical validation","Direct interaction between CLAMP and TRAP was not demonstrated"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Whether CLAMP acts alone or in a complex was unknown; work in T. gondii identified a conserved CLAMP-SPATR-CLIP microneme complex linked to rhoptry discharge, providing a candidate molecular context for CLAMP function.","evidence":"Biochemical/genetic complex identification and knockdown showing rhoptry discharge defect in T. gondii; phylogenetic analysis; inference from prior P. falciparum blood-stage data","pmids":["37886905"],"confidence":"Medium","gaps":["Complex membership was established in T. gondii, not directly in Plasmodium","Direct role of Plasmodium CLAMP in rhoptry discharge was not tested biochemically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The blood-stage essentiality inferred from refractory deletion needed direct confirmation; a clean conditional KO confirmed CLAMP is required for merozoite erythrocyte invasion.","evidence":"Conditional KO using constitutive Cas9 plus rapamycin-inducible DiCre in P. berghei; growth and invasion assays","pmids":["39849074"],"confidence":"Medium","gaps":["Single confirmatory study","Mechanistic step of invasion failure not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"claim":"Whether the CLAMP-CLIP-SPATR complex functions as a unit in Plasmodium was open; clip deletion phenocopying clamp deletion across all invasive stages supported a conserved, functionally coupled complex.","evidence":"CRISPR-assisted conditional deletion (DiCre) of clip in P. berghei blood and transmission stages; growth, motility, traversal, and invasion assays (preprint)","pmids":["41929181"],"confidence":"Medium","gaps":["Preprint, single lab, not yet peer-reviewed","Phenocopy is genetic; direct physical interaction of CLAMP and CLIP in Plasmodium not biochemically shown here","The shared molecular function of the complex remains undefined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct biochemical activity of CLAMP—how it regulates adhesin shedding and/or rhoptry discharge and whether it binds TRAP, CLIP, or SPATR directly in Plasmodium—remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model or direct binding data for Plasmodium CLAMP","Causality between CLAMP loss and reduced TRAP shedding unestablished","No direct demonstration of CLAMP-dependent rhoptry discharge in Plasmodium"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CLAMP-CLIP-SPATR microneme complex (established in T. gondii; genetically supported in P. berghei)"],"partners":["CLIP (CLAMP-LINKED INVASION PROTEIN)","SPATR","TRAP (PARTIAL MICRONEME COLOCALIZATION IN SPOROZOITES)"],"other_free_text":["Essential for P. falciparum and P. berghei asexual blood-stage growth and merozoite erythrocyte invasion","Required for P. berghei sporozoite gliding motility, cell traversal, and invasion of salivary glands and hepatocytes","CLAMP-deficient sporozoites show reduced shedding of the adhesin TRAP","CLAMP and CLIP orthologs are ubiquitous across apicomplexans","clip deletion phenocopies clamp deletion across all invasive stages in P. berghei"]}},"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":21,"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":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLAMP"],"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":2,"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"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5091,"output_tokens":1665,"usd":0.020124,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6706,"output_tokens":3101,"usd":0.055528,"stage2_stop_reason":"end_turn"},"total_usd":0.075652,"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\": 2023,\n      \"finding\": \"CLAMP (PF3D7_1367200) is essential for Plasmodium falciparum asexual blood stage growth; conventional gene deletion is refractory, indicating an essential role in erythrocyte invasion.\",\n      \"method\": \"Conditional genome editing (dimerisable Cre recombinase) in P. berghei; gene deletion and functional analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined invasion phenotype, replicated across two independent studies (PMID:36928686 and PMID:39849074)\",\n      \"pmids\": [\"36928686\", \"39849074\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CLAMP is essential for gliding motility and invasion of mosquito salivary glands and mammalian hepatocytes by P. berghei sporozoites; CLAMP-deficient sporozoites show reduced shedding of the sporozoite adhesin TRAP.\",\n      \"method\": \"Conditional gene deletion (DiCre) in P. berghei transmission stages; gliding motility assays, cell traversal assays, productive invasion assays, expansion microscopy for colocalization with TRAP\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with multiple orthogonal phenotypic readouts (motility, cell traversal, invasion) and colocalization evidence in a single rigorous study\",\n      \"pmids\": [\"36928686\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CLAMP partially colocalizes with the adhesin TRAP in a subset of micronemes and accumulates distinctly at the apical tip of P. berghei sporozoites, placing it upstream of host cell invasion.\",\n      \"method\": \"Expansion microscopy and colocalization analysis in P. berghei sporozoites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single microscopy method; localization tied functionally to TRAP shedding defect but without direct biochemical validation\",\n      \"pmids\": [\"36928686\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CLAMP forms a conserved microneme protein complex with SPATR and CLIP (CLAMP-Linked Invasion Protein) in Toxoplasma gondii; phylogenetic analysis indicates that CLAMP and CLIP orthologs are ubiquitous across apicomplexans, and SPATR is also essential for P. falciparum blood-stage invasion.\",\n      \"method\": \"Complex identification (biochemical/genetic analysis in T. gondii); phylogenetic analysis; knockdown of each complex member showing rhoptry discharge defect\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complex membership established in T. gondii with functional validation; P. falciparum CLAMP essentiality inferred from prior blood-stage data; single lab for Plasmodium-specific portion\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Conditional deletion of clamp in P. berghei blood stages (using a dual CRISPR/Cas9 + DiCre parasite line) confirmed the essential role of CLAMP during erythrocyte invasion by merozoites.\",\n      \"method\": \"Conditional KO using constitutive Cas9 + rapamycin-inducible DiCre in P. berghei; growth and invasion assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined invasion phenotype; single lab, confirmatory study\",\n      \"pmids\": [\"39849074\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CLIP (the CLAMP-linked invasion protein) and CLAMP form a conserved complex in P. berghei; deletion of clip phenocopies deletion of clamp, causing defects in erythrocyte invasion by merozoites, salivary gland invasion by sporozoites, cell traversal, hepatocyte invasion, and gliding motility, supporting a conserved CLAMP-CLIP-SPATR complex essential across invasive stages.\",\n      \"method\": \"CRISPR-assisted conditional gene deletion (DiCre) of clip in P. berghei blood and transmission stages; growth assays, gliding motility assays, cell traversal, invasion assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with multiple orthogonal phenotypic readouts; preprint, single lab, not yet peer-reviewed\",\n      \"pmids\": [\"41929181\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1367200 (CLAMP) is a conserved microneme protein essential for host cell invasion across multiple Plasmodium life-cycle stages (merozoites, sporozoites), where it functions upstream of host-cell contact—likely regulating rhoptry discharge and adhesin (TRAP) secretion/shedding—as part of a conserved complex with CLIP and SPATR; its apical tip localization in sporozoites and the phenotypic recapitulation by CLIP deletion support a shared CLAMP-CLIP-SPATR complex mechanism for invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1367200 (CLAMP) is a conserved microneme protein essential for host-cell invasion across multiple Plasmodium life-cycle stages [#0, #1]. In P. falciparum and P. berghei, CLAMP is required for asexual blood-stage growth, with conventional deletion refractory and conditional deletion establishing an essential role in erythrocyte invasion by merozoites [#0, #4]. In P. berghei transmission stages, CLAMP is additionally required for sporozoite gliding motility, cell traversal, and invasion of mosquito salivary glands and mammalian hepatocytes, positioning it upstream of productive host-cell entry [#1]. CLAMP-deficient sporozoites show reduced shedding of the adhesin TRAP, and CLAMP partially colocalizes with TRAP in a subset of micronemes while accumulating distinctly at the apical tip [#1, #2]. In Toxoplasma gondii, CLAMP forms a conserved microneme complex with SPATR and CLIP, and both CLAMP and CLIP orthologs are distributed across apicomplexans; deletion of clip in P. berghei phenocopies clamp deletion across all invasive stages, supporting a shared CLAMP-CLIP-SPATR complex mechanism for invasion [#3, #5]. Beyond its essentiality, its complex membership, and its correlation with TRAP shedding, the direct biochemical mechanism by which PF3D7_1367200 CLAMP regulates invasion has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether CLAMP has an essential role in Plasmodium was unknown; conditional deletion established that it is required for asexual blood-stage growth and erythrocyte invasion.\",\n      \"evidence\": \"Conditional genome editing (DiCre) in P. berghei with refractory conventional deletion in P. falciparum; growth and invasion analysis\",\n      \"pmids\": [\"36928686\", \"39849074\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular activity of CLAMP during invasion was not defined\",\n        \"Whether the invasion defect is due to failed attachment, rhoptry discharge, or motility was not resolved at this stage\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unclear whether CLAMP function extended beyond blood stages; conditional deletion in transmission stages showed it is required for sporozoite gliding, traversal, and invasion, generalizing its role to multiple invasive stages.\",\n      \"evidence\": \"Conditional gene deletion (DiCre) in P. berghei transmission stages with gliding motility, cell traversal, and productive invasion assays\",\n      \"pmids\": [\"36928686\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The step at which motility/invasion fails was not mechanistically dissected\",\n        \"Whether reduced TRAP shedding is causal or a downstream consequence was not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The subcellular basis for CLAMP's invasion role was unknown; expansion microscopy placed CLAMP at the sporozoite apical tip and in a subset of TRAP-containing micronemes, tying it to adhesin secretion.\",\n      \"evidence\": \"Expansion microscopy and colocalization with TRAP in P. berghei sporozoites\",\n      \"pmids\": [\"36928686\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization rests on a single microscopy method without direct biochemical validation\",\n        \"Direct interaction between CLAMP and TRAP was not demonstrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether CLAMP acts alone or in a complex was unknown; work in T. gondii identified a conserved CLAMP-SPATR-CLIP microneme complex linked to rhoptry discharge, providing a candidate molecular context for CLAMP function.\",\n      \"evidence\": \"Biochemical/genetic complex identification and knockdown showing rhoptry discharge defect in T. gondii; phylogenetic analysis; inference from prior P. falciparum blood-stage data\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Complex membership was established in T. gondii, not directly in Plasmodium\",\n        \"Direct role of Plasmodium CLAMP in rhoptry discharge was not tested biochemically\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The blood-stage essentiality inferred from refractory deletion needed direct confirmation; a clean conditional KO confirmed CLAMP is required for merozoite erythrocyte invasion.\",\n      \"evidence\": \"Conditional KO using constitutive Cas9 plus rapamycin-inducible DiCre in P. berghei; growth and invasion assays\",\n      \"pmids\": [\"39849074\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single confirmatory study\",\n        \"Mechanistic step of invasion failure not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Whether the CLAMP-CLIP-SPATR complex functions as a unit in Plasmodium was open; clip deletion phenocopying clamp deletion across all invasive stages supported a conserved, functionally coupled complex.\",\n      \"evidence\": \"CRISPR-assisted conditional deletion (DiCre) of clip in P. berghei blood and transmission stages; growth, motility, traversal, and invasion assays (preprint)\",\n      \"pmids\": [\"41929181\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint, single lab, not yet peer-reviewed\",\n        \"Phenocopy is genetic; direct physical interaction of CLAMP and CLIP in Plasmodium not biochemically shown here\",\n        \"The shared molecular function of the complex remains undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical activity of CLAMP—how it regulates adhesin shedding and/or rhoptry discharge and whether it binds TRAP, CLIP, or SPATR directly in Plasmodium—remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model or direct binding data for Plasmodium CLAMP\",\n        \"Causality between CLAMP loss and reduced TRAP shedding unestablished\",\n        \"No direct demonstration of CLAMP-dependent rhoptry discharge in Plasmodium\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0071702\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"CLAMP-CLIP-SPATR microneme complex (established in T. gondii; genetically supported in P. berghei)\"\n    ],\n    \"partners\": [\n      \"CLIP (CLAMP-Linked Invasion Protein)\",\n      \"SPATR\",\n      \"TRAP (partial microneme colocalization in sporozoites)\"\n    ],\n    \"other_free_text\": [\n      \"Essential for P. falciparum and P. berghei asexual blood-stage growth and merozoite erythrocyte invasion\",\n      \"Required for P. berghei sporozoite gliding motility, cell traversal, and invasion of salivary glands and hepatocytes\",\n      \"CLAMP-deficient sporozoites show reduced shedding of the adhesin TRAP\",\n      \"CLAMP and CLIP orthologs are ubiquitous across apicomplexans\",\n      \"clip deletion phenocopies clamp deletion across all invasive stages in P. berghei\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1367200","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 4 of 4 cited papers name other catalogue genes (PF3D7_1030200, PF3D7_0212600, PF3D7_1335900). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1367200","name":null,"product":"CLAMP domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1143100","name":null,"product":"CLAMP domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1104000","name":null,"product":"CLAMP domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}