{"gene":"PF3D7_0613800","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2025,"finding":"PfAP2-06B (PF3D7_0613800) binds to the genomic loci of pfk13 and pfcrt, as demonstrated by ChIP-seq using anti-GFP antibodies in 3D7/PfAP2-06B-GFP schizont-stage parasites.","method":"ChIP-seq with GFP-tagged PfAP2-06B in P. falciparum schizonts","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — ChIP-seq is a rigorous in vivo binding method, but reported from a single lab with no independent replication","pmids":["39835275"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2025,"finding":"Conditional knockdown of PfAP2-06B (PF3D7_0613800) does not alter parasite sensitivity to artemisinin or quinolines, and neither the K3124R mutation nor conditional knockdown of PfAP2-06B modulates pfk13 or pfcrt expression, demonstrating that PfAP2-06B is not functionally required for artemisinin or quinoline resistance despite binding to these loci.","method":"CRISPR/Cas9-mediated K3124R point mutation and conditional knockdown of PfAP2-06B; drug susceptibility assays in P. falciparum 3D7","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Two orthogonal genetic approaches (point mutation + conditional KD) in a single lab; negative result is mechanistically informative","pmids":["39835275"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2025,"finding":"Conditional knockdown of PfAP2-06B (PF3D7_0613800) results in a defect in asexual blood-stage growth and impaired erythrocyte invasion, establishing PfAP2-06B as an essential regulator of intraerythrocytic development.","method":"Conditional knockdown of PfAP2-06B followed by growth and invasion assays in P. falciparum","journal":"Pathogens (Basel, Switzerland)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Conditional KD with defined cellular phenotype (invasion defect), single lab, no independent replication","pmids":["41305314"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Bulk RNA-seq of PfAP2-06B (PF3D7_0613800) conditional knockdown parasites revealed that PfAP2-06B modulates the expression of invasion-related genes during the schizont stage, indicating it regulates erythrocyte invasion indirectly through transcriptional control.","method":"Bulk RNA sequencing and single-cell RNA sequencing of conditional PfAP2-06B knockdown P. falciparum parasites","journal":"Pathogens (Basel, Switzerland)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Two transcriptomic approaches (bulk and scRNA-seq) from a single lab, no independent replication","pmids":["41305314"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfAP2-06B (PF3D7_0613800) is a sequence-specific AP2-domain transcription factor in P. falciparum that binds the promoter regions of pfk13 and pfcrt in schizonts, is essential for normal asexual blood-stage growth and erythrocyte invasion through transcriptional regulation of invasion-related genes, but does not functionally confer artemisinin or quinoline resistance despite occupying those loci."},"narrative":{"mechanistic_narrative":"PF3D7_0613800 (PfAP2-06B) is a sequence-specific AP2-domain transcription factor of Plasmodium falciparum that governs asexual intraerythrocytic development and erythrocyte invasion through transcriptional control [PMID:41305314]. In 3D7 schizonts, ChIP-seq shows it occupies the genomic loci of pfk13 and pfcrt [PMID:39835275], yet conditional knockdown and a K3124R point mutation neither alter parasite sensitivity to artemisinin or quinolines nor change pfk13 or pfcrt expression, establishing that PfAP2-06B is not functionally required for artemisinin or quinoline resistance despite binding these loci [PMID:39835275]. Its essential contribution instead lies in intraerythrocytic growth: conditional knockdown produces an asexual blood-stage growth defect and impaired erythrocyte invasion [PMID:41305314], and transcriptomic profiling of the knockdown reveals dysregulation of invasion-related genes during the schizont stage, indicating PfAP2-06B controls invasion indirectly via schizont-stage transcriptional regulation [PMID:41305314]. Beyond these findings, the DNA-binding motif, direct target set, and any protein partners of PfAP2-06B have not been characterized in the available corpus.","teleology":[{"year":2025,"claim":"To ask whether PfAP2-06B directly engages known drug-resistance loci, its genome-wide occupancy was mapped, revealing binding at the pfk13 and pfcrt loci and placing this factor at the promoters of resistance-associated genes.","evidence":"ChIP-seq with GFP-tagged PfAP2-06B in P. falciparum 3D7 schizonts","pmids":["39835275"],"confidence":"Medium","gaps":["Genome-wide binding beyond pfk13/pfcrt and the underlying DNA sequence motif not defined","Single lab, no independent replication","Occupancy shown only in schizonts, not across the cycle"],"attribution":[]},{"year":2025,"claim":"To test whether locus occupancy translates into functional control of drug resistance, orthogonal genetic perturbations showed PfAP2-06B does not confer artemisinin or quinoline resistance, decoupling physical binding from regulatory function at these loci.","evidence":"CRISPR/Cas9 K3124R point mutation and conditional knockdown with drug susceptibility assays in P. falciparum 3D7","pmids":["39835275"],"confidence":"Medium","gaps":["Why the factor binds pfk13/pfcrt without regulating them remains unexplained","Negative result from a single lab","Whether binding has any conditional or stress-dependent function untested"],"attribution":[]},{"year":2025,"claim":"To define the essential role of PfAP2-06B, conditional knockdown established it as a regulator of asexual growth and erythrocyte invasion, tying the factor to a concrete cellular process.","evidence":"Conditional knockdown followed by growth and invasion assays in P. falciparum","pmids":["41305314"],"confidence":"Medium","gaps":["Molecular step of invasion affected not resolved","Single lab, no independent replication","Strain not specified"],"attribution":[]},{"year":2025,"claim":"To determine how PfAP2-06B controls invasion, transcriptomics of the knockdown showed dysregulation of invasion-related genes at the schizont stage, indicating the invasion defect arises from transcriptional control rather than a direct structural role.","evidence":"Bulk and single-cell RNA-seq of conditional PfAP2-06B knockdown P. falciparum","pmids":["41305314"],"confidence":"Medium","gaps":["Direct versus indirect targets not distinguished by integrating with ChIP-seq","DNA-binding motif not identified","Single lab, no independent replication"],"attribution":[]},{"year":null,"claim":"The DNA sequence motif recognized by PfAP2-06B, its genome-wide direct target set, and any protein interaction partners remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No consensus binding motif reported","ChIP-seq and RNA-seq datasets not integrated to distinguish direct targets","No interacting proteins or complex membership characterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Binds pfk13 and pfcrt loci in schizonts but is not functionally required for artemisinin or quinoline resistance [#0, #1].","Essential for asexual blood-stage growth and erythrocyte invasion via schizont-stage regulation of invasion-related genes [#2, #3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24572369","id":"PMC_24572369","title":"A transcriptional switch underlies commitment to sexual development in malaria parasites.","date":"2014","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/24572369","citation_count":395,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfAP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16040597","id":"PMC_16040597","title":"Discovery of the principal specific transcription factors of Apicomplexa and 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Section D, Structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/39820027","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40455742","id":"PMC_40455742","title":"Heterochromatin de novo formation and maintenance in Plasmodium falciparum.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/40455742","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfAP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40568120","id":"PMC_40568120","title":"A single valine to leucine switch disrupts Plasmodium falciparum AP2-G DNA binding and reveals GDV1's role in ap2-g activation.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40568120","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41332573","id":"PMC_41332573","title":"A divergent Plasmodium NEK4 acts as a key regulator driving the early events of meiosis.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41332573","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41510253","id":"PMC_41510253","title":"A divergent Plasmodium NEK4 acts as a key regulator driving the early events of meiosis.","date":"2025","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/41510253","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40558503","id":"PMC_40558503","title":"GCN5 Is a Master Regulator of Gene Expression in the Malaria Parasite Plasmodium falciparum.","date":"2025","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/40558503","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41305314","id":"PMC_41305314","title":"An ApiAP2 Family Transcriptional Factor PfAP2-06B Regulates Erythrocyte Invasion Indirectly in Plasmodium falciparum.","date":"2025","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/41305314","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfAP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38966997","id":"PMC_38966997","title":"DNA sequence and chromatin differentiate sequence-specific transcription factor binding in the human malaria parasite Plasmodium falciparum.","date":"2024","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/38966997","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfAP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":46614,"output_tokens":1496,"usd":0.081141,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5976,"output_tokens":1936,"usd":0.03914,"stage2_stop_reason":"end_turn"},"total_usd":0.120281,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully identify which papers are actually about PF3D7_0613800 (AP2-06B). This gene is mentioned by name in only a few papers in this corpus. The vast majority of papers are about other ApiAP2 family members (PfAP2-G, PfAP2-I, PfAP2-G2, AP2-O, etc.) or the AP2 adaptor complex (pfap2-mu). I must not conflate these with PF3D7_0613800.\n\nPapers directly about PF3D7_0613800:\n- Paper [83]: Explicitly names \"AP2-06B (PF3D7_0613800)\" and performs ChIP-seq, K3124R mutation, and conditional knockdown.\n- Paper [90]: Explicitly names \"PfAP2-06B (PF3D7_0613800)\" and performs conditional knockdown, RNA-seq, scRNA-seq.\n- Paper [91]: Names \"PfAP2-G and PfAP2-EXP\" as the focus but also studies CACACA and GTGCAC motif binders — need to check if PF3D7_0613800 is among them. The abstract doesn't explicitly name PF3D7_0613800, so I cannot confirm.\n\nAll other papers describe other genes. I will extract only from papers [83] and [90].\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"PfAP2-06B (PF3D7_0613800) binds to the genomic loci of pfk13 and pfcrt, as demonstrated by ChIP-seq using anti-GFP antibodies in 3D7/PfAP2-06B-GFP schizont-stage parasites.\",\n      \"method\": \"ChIP-seq with GFP-tagged PfAP2-06B in P. falciparum schizonts\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — ChIP-seq is a rigorous in vivo binding method, but reported from a single lab with no independent replication\",\n      \"pmids\": [\"39835275\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Conditional knockdown of PfAP2-06B (PF3D7_0613800) does not alter parasite sensitivity to artemisinin or quinolines, and neither the K3124R mutation nor conditional knockdown of PfAP2-06B modulates pfk13 or pfcrt expression, demonstrating that PfAP2-06B is not functionally required for artemisinin or quinoline resistance despite binding to these loci.\",\n      \"method\": \"CRISPR/Cas9-mediated K3124R point mutation and conditional knockdown of PfAP2-06B; drug susceptibility assays in P. falciparum 3D7\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Two orthogonal genetic approaches (point mutation + conditional KD) in a single lab; negative result is mechanistically informative\",\n      \"pmids\": [\"39835275\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Conditional knockdown of PfAP2-06B (PF3D7_0613800) results in a defect in asexual blood-stage growth and impaired erythrocyte invasion, establishing PfAP2-06B as an essential regulator of intraerythrocytic development.\",\n      \"method\": \"Conditional knockdown of PfAP2-06B followed by growth and invasion assays in P. falciparum\",\n      \"journal\": \"Pathogens (Basel, Switzerland)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Conditional KD with defined cellular phenotype (invasion defect), single lab, no independent replication\",\n      \"pmids\": [\"41305314\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Bulk RNA-seq of PfAP2-06B (PF3D7_0613800) conditional knockdown parasites revealed that PfAP2-06B modulates the expression of invasion-related genes during the schizont stage, indicating it regulates erythrocyte invasion indirectly through transcriptional control.\",\n      \"method\": \"Bulk RNA sequencing and single-cell RNA sequencing of conditional PfAP2-06B knockdown P. falciparum parasites\",\n      \"journal\": \"Pathogens (Basel, Switzerland)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Two transcriptomic approaches (bulk and scRNA-seq) from a single lab, no independent replication\",\n      \"pmids\": [\"41305314\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfAP2-06B (PF3D7_0613800) is a sequence-specific AP2-domain transcription factor in P. falciparum that binds the promoter regions of pfk13 and pfcrt in schizonts, is essential for normal asexual blood-stage growth and erythrocyte invasion through transcriptional regulation of invasion-related genes, but does not functionally confer artemisinin or quinoline resistance despite occupying those loci.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0613800 (PfAP2-06B) is a sequence-specific AP2-domain transcription factor of Plasmodium falciparum that governs asexual intraerythrocytic development and erythrocyte invasion through transcriptional control [#2, #3]. In 3D7 schizonts, ChIP-seq shows it occupies the genomic loci of pfk13 and pfcrt [#0], yet conditional knockdown and a K3124R point mutation neither alter parasite sensitivity to artemisinin or quinolines nor change pfk13 or pfcrt expression, establishing that PfAP2-06B is not functionally required for artemisinin or quinoline resistance despite binding these loci [#1]. Its essential contribution instead lies in intraerythrocytic growth: conditional knockdown produces an asexual blood-stage growth defect and impaired erythrocyte invasion [#2], and transcriptomic profiling of the knockdown reveals dysregulation of invasion-related genes during the schizont stage, indicating PfAP2-06B controls invasion indirectly via schizont-stage transcriptional regulation [#3]. Beyond these findings, the DNA-binding motif, direct target set, and any protein partners of PfAP2-06B have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"To ask whether PfAP2-06B directly engages known drug-resistance loci, its genome-wide occupancy was mapped, revealing binding at the pfk13 and pfcrt loci and placing this factor at the promoters of resistance-associated genes.\",\n      \"evidence\": \"ChIP-seq with GFP-tagged PfAP2-06B in P. falciparum 3D7 schizonts\",\n      \"pmids\": [\"39835275\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Genome-wide binding beyond pfk13/pfcrt and the underlying DNA sequence motif not defined\", \"Single lab, no independent replication\", \"Occupancy shown only in schizonts, not across the cycle\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To test whether locus occupancy translates into functional control of drug resistance, orthogonal genetic perturbations showed PfAP2-06B does not confer artemisinin or quinoline resistance, decoupling physical binding from regulatory function at these loci.\",\n      \"evidence\": \"CRISPR/Cas9 K3124R point mutation and conditional knockdown with drug susceptibility assays in P. falciparum 3D7\",\n      \"pmids\": [\"39835275\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Why the factor binds pfk13/pfcrt without regulating them remains unexplained\", \"Negative result from a single lab\", \"Whether binding has any conditional or stress-dependent function untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To define the essential role of PfAP2-06B, conditional knockdown established it as a regulator of asexual growth and erythrocyte invasion, tying the factor to a concrete cellular process.\",\n      \"evidence\": \"Conditional knockdown followed by growth and invasion assays in P. falciparum\",\n      \"pmids\": [\"41305314\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular step of invasion affected not resolved\", \"Single lab, no independent replication\", \"Strain not specified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To determine how PfAP2-06B controls invasion, transcriptomics of the knockdown showed dysregulation of invasion-related genes at the schizont stage, indicating the invasion defect arises from transcriptional control rather than a direct structural role.\",\n      \"evidence\": \"Bulk and single-cell RNA-seq of conditional PfAP2-06B knockdown P. falciparum\",\n      \"pmids\": [\"41305314\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect targets not distinguished by integrating with ChIP-seq\", \"DNA-binding motif not identified\", \"Single lab, no independent replication\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The DNA sequence motif recognized by PfAP2-06B, its genome-wide direct target set, and any protein interaction partners remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No consensus binding motif reported\", \"ChIP-seq and RNA-seq datasets not integrated to distinguish direct targets\", \"No interacting proteins or complex membership characterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003700\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0000976\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0007015\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Binds pfk13 and pfcrt loci in schizonts but is not functionally required for artemisinin or quinoline resistance [#0, #1].\",\n      \"Essential for asexual blood-stage growth and erythrocyte invasion via schizont-stage regulation of invasion-related genes [#2, #3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0613800","name":null,"product":"AP2 domain transcription factor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0112100","name":null,"product":"AP2 domain transcription factor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1136200","name":null,"product":"AP2 domain transcription factor, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}