{"gene":"PF3D7_1434400","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2023,"finding":"In Toxoplasma gondii tachyzoites, CLAMP forms a distinct microneme protein complex with SPATR and CLIP (PF3D7_1434400 ortholog). Knockdown of any member of this CLAMP complex affects rhoptry discharge without impacting parasite adhesion or microneme protein secretion. Phylogenetic analysis indicates that orthologs of CLAMP and CLIP are ubiquitous across apicomplexans.","method":"Protein complex identification (co-immunoprecipitation/pulldown), conditional knockdown, rhoptry discharge assay, adhesion assay, microneme secretion assay, phylogenetic analysis","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal complex identification with functional knockdown in Toxoplasma; CLIP function in Plasmodium not directly tested in this paper, only inferred from conservation","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"Conditional deletion of clip (PF3D7_1434400 ortholog) in P. berghei blood stages impaired parasite growth and prevented erythrocyte invasion by merozoites. In transmission stages, deletion of clip did not affect sporozoite development in mosquitoes but dramatically reduced invasion of mosquito salivary glands. CLIP-deficient sporozoites were also impaired in cell traversal and productive invasion of mammalian hepatocytes, associated with a defect in gliding motility, phenocopying CLAMP-deficient parasites. These results support a conserved role of the CLAMP-CLIP-SPATR complex across invasive stages.","method":"CRISPR-assisted conditional genome editing (DiCre-based clip deletion), erythrocyte invasion assay, sporozoite salivary gland invasion assay, cell traversal assay, hepatocyte invasion assay, gliding motility assay","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with multiple orthogonal phenotypic readouts across life cycle stages in a single lab preprint; not yet peer-reviewed","pmids":["41929181"],"is_preprint":true,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"CLIP (PF3D7_1434400) is a microneme protein that forms a conserved complex with CLAMP and SPATR; in Plasmodium berghei, conditional deletion of CLIP blocks erythrocyte invasion by merozoites and abrogates salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility in sporozoites, placing CLIP as an essential component of the CLAMP complex required for rhoptry discharge and host cell invasion across invasive zoite stages."},"narrative":{"mechanistic_narrative":"PF3D7_1434400 (CLIP) is a component of a conserved apicomplexan microneme protein complex that couples parasite invasive machinery to host cell entry [PMID:37886905]. In Toxoplasma gondii, the CLIP ortholog partners with CLAMP and SPATR to form a distinct microneme complex, and knockdown of complex members blocks rhoptry discharge without impairing parasite adhesion or microneme secretion, placing the complex specifically at the rhoptry-discharge step of invasion [PMID:37886905]. In Plasmodium berghei, conditional deletion of clip impairs blood-stage growth and prevents merozoite invasion of erythrocytes, and in transmission stages abolishes sporozoite invasion of mosquito salivary glands and productive invasion of mammalian hepatocytes together with defects in cell traversal and gliding motility, phenocopying CLAMP-deficient parasites and establishing CLIP as essential for host cell invasion across invasive zoite stages [PMID:41929181]. Beyond its membership in the CLAMP-CLIP-SPATR complex and these invasion phenotypes, no further mechanistic detail for PF3D7_1434400 itself has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing whether CLIP belongs to a defined invasion complex and at which step it acts distinguished a general adhesion role from a specific rhoptry-discharge role.","evidence":"Co-immunoprecipitation, conditional knockdown, and rhoptry discharge/adhesion/secretion assays in Toxoplasma gondii tachyzoites, with phylogenetic analysis","pmids":["37886905"],"confidence":"Medium","gaps":["CLIP function was tested in Toxoplasma, not directly in Plasmodium; the Plasmodium role was inferred only from conservation","The molecular mechanism by which the CLAMP-CLIP-SPATR complex enables rhoptry discharge is not defined","No structural model of the complex or of CLIP's contribution to it"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Direct loss-of-function of clip in Plasmodium tested whether the complex role is conserved and stage-specific, showing CLIP is required for invasion across the parasite life cycle rather than in a single stage.","evidence":"DiCre-based conditional clip deletion in P. berghei with erythrocyte invasion, salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility assays (preprint)","pmids":["41929181"],"confidence":"Medium","gaps":["Not yet peer-reviewed; single-lab preprint","Does not resolve whether CLIP acts through the same rhoptry-discharge mechanism in Plasmodium as shown for the complex in Toxoplasma","The link between the gliding motility defect and the invasion/traversal defects is not mechanistically dissected"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How CLIP itself contributes biochemically to the CLAMP-CLIP-SPATR complex and to rhoptry discharge remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined molecular activity for CLIP beyond complex membership","No structural data on CLIP or its interface with CLAMP and SPATR","Mechanistic basis of the gliding motility defect in CLIP-deficient sporozoites is unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CLAMP-CLIP-SPATR microneme complex"],"partners":["CLAMP","SPATR"],"other_free_text":["CLIP is required for rhoptry discharge as part of the CLAMP complex in Toxoplasma gondii, without affecting adhesion or microneme secretion [#0].","In Plasmodium berghei, conditional clip deletion blocks merozoite erythrocyte invasion, sporozoite salivary gland invasion, hepatocyte invasion, cell traversal, and gliding motility, phenocopying CLAMP loss [#1].","Orthologs of CLIP and CLAMP are conserved across apicomplexans [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30616642","id":"PMC_30616642","title":"Chromatin changes in Anopheles gambiae induced by Plasmodium falciparum infection.","date":"2019","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/30616642","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLIP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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","CLIP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"32330198","id":"PMC_32330198","title":"Broad spectrum immunomodulatory effects of Anopheles gambiae microRNAs and their use for transgenic suppression of Plasmodium.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32330198","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CLIP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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"],"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","CLIP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6176,"output_tokens":822,"usd":0.015429,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5500,"output_tokens":1754,"usd":0.035675,"stage2_stop_reason":"end_turn"},"total_usd":0.051104,"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\": \"In Toxoplasma gondii tachyzoites, CLAMP forms a distinct microneme protein complex with SPATR and CLIP (PF3D7_1434400 ortholog). Knockdown of any member of this CLAMP complex affects rhoptry discharge without impacting parasite adhesion or microneme protein secretion. Phylogenetic analysis indicates that orthologs of CLAMP and CLIP are ubiquitous across apicomplexans.\",\n      \"method\": \"Protein complex identification (co-immunoprecipitation/pulldown), conditional knockdown, rhoptry discharge assay, adhesion assay, microneme secretion assay, phylogenetic analysis\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal complex identification with functional knockdown in Toxoplasma; CLIP function in Plasmodium not directly tested in this paper, only inferred from conservation\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Conditional deletion of clip (PF3D7_1434400 ortholog) in P. berghei blood stages impaired parasite growth and prevented erythrocyte invasion by merozoites. In transmission stages, deletion of clip did not affect sporozoite development in mosquitoes but dramatically reduced invasion of mosquito salivary glands. CLIP-deficient sporozoites were also impaired in cell traversal and productive invasion of mammalian hepatocytes, associated with a defect in gliding motility, phenocopying CLAMP-deficient parasites. These results support a conserved role of the CLAMP-CLIP-SPATR complex across invasive stages.\",\n      \"method\": \"CRISPR-assisted conditional genome editing (DiCre-based clip deletion), erythrocyte invasion assay, sporozoite salivary gland invasion assay, cell traversal assay, hepatocyte invasion assay, gliding motility assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with multiple orthogonal phenotypic readouts across life cycle stages in a single lab preprint; not yet peer-reviewed\",\n      \"pmids\": [\"41929181\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CLIP (PF3D7_1434400) is a microneme protein that forms a conserved complex with CLAMP and SPATR; in Plasmodium berghei, conditional deletion of CLIP blocks erythrocyte invasion by merozoites and abrogates salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility in sporozoites, placing CLIP as an essential component of the CLAMP complex required for rhoptry discharge and host cell invasion across invasive zoite stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1434400 (CLIP) is a component of a conserved apicomplexan microneme protein complex that couples parasite invasive machinery to host cell entry [#0]. In Toxoplasma gondii, the CLIP ortholog partners with CLAMP and SPATR to form a distinct microneme complex, and knockdown of complex members blocks rhoptry discharge without impairing parasite adhesion or microneme secretion, placing the complex specifically at the rhoptry-discharge step of invasion [#0]. In Plasmodium berghei, conditional deletion of clip impairs blood-stage growth and prevents merozoite invasion of erythrocytes, and in transmission stages abolishes sporozoite invasion of mosquito salivary glands and productive invasion of mammalian hepatocytes together with defects in cell traversal and gliding motility, phenocopying CLAMP-deficient parasites and establishing CLIP as essential for host cell invasion across invasive zoite stages [#1]. Beyond its membership in the CLAMP-CLIP-SPATR complex and these invasion phenotypes, no further mechanistic detail for PF3D7_1434400 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing whether CLIP belongs to a defined invasion complex and at which step it acts distinguished a general adhesion role from a specific rhoptry-discharge role.\",\n      \"evidence\": \"Co-immunoprecipitation, conditional knockdown, and rhoptry discharge/adhesion/secretion assays in Toxoplasma gondii tachyzoites, with phylogenetic analysis\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"CLIP function was tested in Toxoplasma, not directly in Plasmodium; the Plasmodium role was inferred only from conservation\",\n        \"The molecular mechanism by which the CLAMP-CLIP-SPATR complex enables rhoptry discharge is not defined\",\n        \"No structural model of the complex or of CLIP's contribution to it\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Direct loss-of-function of clip in Plasmodium tested whether the complex role is conserved and stage-specific, showing CLIP is required for invasion across the parasite life cycle rather than in a single stage.\",\n      \"evidence\": \"DiCre-based conditional clip deletion in P. berghei with erythrocyte invasion, salivary gland invasion, cell traversal, hepatocyte invasion, and gliding motility assays (preprint)\",\n      \"pmids\": [\"41929181\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Not yet peer-reviewed; single-lab preprint\",\n        \"Does not resolve whether CLIP acts through the same rhoptry-discharge mechanism in Plasmodium as shown for the complex in Toxoplasma\",\n        \"The link between the gliding motility defect and the invasion/traversal defects is not mechanistically dissected\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CLIP itself contributes biochemically to the CLAMP-CLIP-SPATR complex and to rhoptry discharge remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined molecular activity for CLIP beyond complex membership\",\n        \"No structural data on CLIP or its interface with CLAMP and SPATR\",\n        \"Mechanistic basis of the gliding motility defect in CLIP-deficient sporozoites is unknown\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"CLAMP-CLIP-SPATR microneme complex\"],\n    \"partners\": [\"CLAMP\", \"SPATR\"],\n    \"other_free_text\": [\n      \"CLIP is required for rhoptry discharge as part of the CLAMP complex in Toxoplasma gondii, without affecting adhesion or microneme secretion [#0].\",\n      \"In Plasmodium berghei, conditional clip deletion blocks merozoite erythrocyte invasion, sporozoite salivary gland invasion, hepatocyte invasion, cell traversal, and gliding motility, phenocopying CLAMP loss [#1].\",\n      \"Orthologs of CLIP and CLAMP are conserved across apicomplexans [#0].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1434400","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_0212600, PF3D7_1030200). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1434400","name":null,"product":"CLAMP-linked invasion protein CLIP, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1010400","name":null,"product":"conserved protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0421000","name":null,"product":"conserved protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}