{"gene":"PF3D7_1414100","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2023,"finding":"In a global barcoded-mutant screen, PF3D7_1414100 (identified as a female-determining zinc-finger protein) was found to be essential for female sexual form development in Plasmodium; protein interactors of this zinc-finger protein indicate it participates in germ-granule-like ribonucleoprotein complexes, complementing transcriptional processes in the regulation of female development.","method":"Global screen of barcoded mutants; single-cell transcriptomics of mutant parasites; protein interaction network analysis","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — barcoded mutant screen with single-cell transcriptomics and protein interactor identification, single study but multiple orthogonal methods; gene identity as PF3D7_1414100 inferred from screen context, not explicitly stated in abstract","pmids":["36634679"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"The P. falciparum homolog of Toxoplasma gondii TgZNF2 (a C2H2 zinc finger protein) was able to efficiently rescue the lethal proliferation defect caused by TgZNF2 depletion in T. gondii, suggesting that the mRNA nuclear export function of this zinc-finger protein is conserved in P. falciparum.","method":"Complementation assay: expression of P. falciparum homolog in inducible TgZNF2-knockout T. gondii parasites; phenotypic rescue of growth defect","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single complementation experiment performed in Toxoplasma (not directly in Plasmodium); identity of the P. falciparum gene as PF3D7_1414100 is inferred but not explicitly confirmed in the abstract","pmids":["27385072"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1414100 is a putative zinc finger protein implicated in female gametocyte development in Plasmodium, where it appears to function within germ-granule-like ribonucleoprotein complexes; its P. falciparum ortholog relationship to TgZNF2 suggests a possible conserved role in polyA+ mRNA nuclear export, but direct mechanistic characterization in Plasmodium itself remains limited."},"narrative":{"mechanistic_narrative":"PF3D7_1414100 is a putative C2H2 zinc finger protein required for female sexual-stage development in Plasmodium; in a global barcoded-mutant screen it was identified as a female-determining factor essential for female gametocyte formation, and its protein interactors place it within germ-granule-like ribonucleoprotein complexes that complement transcriptional programs governing female development [PMID:36634679]. Its P. falciparum ortholog can rescue the lethal proliferation defect of Toxoplasma gondii depleted of the C2H2 zinc finger protein TgZNF2, indicating a conserved mRNA nuclear export function [PMID:27385072]. Beyond these findings, the direct molecular mechanism of PF3D7_1414100 in Plasmodium — its RNA targets, the composition of the ribonucleoprotein complexes it joins, and its subcellular site of action — has not been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Whether the zinc-finger mRNA nuclear export activity defined in Toxoplasma is conserved in Plasmodium was unknown; cross-species complementation established functional conservation of the P. falciparum homolog.","evidence":"Expression of the P. falciparum homolog in inducible TgZNF2-knockout T. gondii, scoring rescue of the growth defect","pmids":["27385072"],"confidence":"Low","gaps":["Complementation was performed in Toxoplasma, not directly in Plasmodium, so the native Plasmodium function was not tested","Identity of the rescuing gene as PF3D7_1414100 is inferred, not explicitly confirmed","No direct demonstration of mRNA export activity or RNA substrates for the Plasmodium protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"The biological role of PF3D7_1414100 in the parasite life cycle was undefined; a genome-scale screen established it as essential for female sexual-form development and placed it in germ-granule-like ribonucleoprotein complexes.","evidence":"Global barcoded-mutant screen with single-cell transcriptomics of mutants and protein interaction network analysis in P. berghei and P. falciparum","pmids":["36634679"],"confidence":"Medium","gaps":["Gene identity as PF3D7_1414100 inferred from screen context, not explicitly stated in the abstract","The RNA cargo and composition of the ribonucleoprotein complexes are not defined","Mechanistic link between the germ-granule association and the proposed mRNA export function is not established"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct molecular mechanism of PF3D7_1414100 in Plasmodium — its RNA targets, the subunits of its ribonucleoprotein complexes, its localization, and whether it directly mediates mRNA nuclear export in the parasite — remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct RNA substrates identified in Plasmodium","No structural or biochemical characterization of the zinc finger's activity","No native localization or reciprocal interaction validation reported"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["germ-granule-like ribonucleoprotein complex [#0]"],"partners":[],"other_free_text":["Essential for female sexual-form (gametocyte) development in Plasmodium [#0]","P. falciparum homolog rescues the lethal defect of TgZNF2-depleted T. gondii, indicating conserved function [#1]","Attributed to PF3D7_1414100 via inference from screen context; identity not explicitly stated in source abstracts [#0, #1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"36634679","id":"PMC_36634679","title":"Regulators of male and female sexual development are critical for the transmission of a malaria parasite.","date":"2023","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/36634679","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34418264","id":"PMC_34418264","title":"Zinc finger proteins of Plasmodium falciparum.","date":"2021","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34418264","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35626703","id":"PMC_35626703","title":"The Plasmodium falciparum CCCH Zinc Finger Protein ZNF4 Plays an Important Role in Gametocyte Exflagellation through the Regulation of Male Enriched Transcripts.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/35626703","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27385072","id":"PMC_27385072","title":"An evolutionary conserved zinc finger protein is involved in Toxoplasma gondii mRNA nuclear export.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27385072","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"27253881","id":"PMC_27253881","title":"Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70-3.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27253881","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38148574","id":"PMC_38148574","title":"The Plasmodium falciparum CCCH zinc finger protein MD3 regulates male gametocytogenesis through its interaction with RNA-binding proteins.","date":"2023","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38148574","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28851851","id":"PMC_28851851","title":"Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response.","date":"2017","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/28851851","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42244567","id":"PMC_42244567","title":"The CCCH-type zinc-finger Pf MD3 promotes translation for malaria parasite transmission.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/42244567","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6723,"output_tokens":1421,"usd":0.020742,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5314,"output_tokens":1703,"usd":0.034572,"stage2_stop_reason":"end_turn"},"total_usd":0.055314,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify which papers are about PF3D7_1414100 (zinc finger protein, putative).\n\nFrom the abstracts:\n- Paper [1]: Mentions a \"female-determining zinc-finger protein\" in P. berghei/falciparum screen — this could be PF3D7_1414100 but it's a global screen paper; it mentions protein interactors of a female-determining zinc-finger protein indicating germ-granule-like ribonucleoprotein complexes.\n- Paper [2]: Review of P. falciparum ZFPs generally — not specific to PF3D7_1414100.\n- Paper [3]: About ZNF4 (CCCH zinc finger) — need to check if this is PF3D7_1414100. ZNF4 is characterized separately; likely a different gene.\n- Paper [4]: About TgZNF2 in Toxoplasma, with P. falciparum homolog mentioned for complementation — could be PF3D7_1414100 if it's the PfZNF2 ortholog.\n- Paper [5]: About PfHep1 and PfHsp70-3 — PfHep1 is a zinc-finger protein but this is a specific named protein (Hep1), not PF3D7_1414100.\n- Paper [6]: About MD3 (CCCH zinc finger) — MD3 interacts with ZNF4, GD1, MD1. MD3 is a specific named protein.\n- Paper [7]: About PbZfp (C2H2 zinc finger in P. berghei) — could be PF3D7_1414100 ortholog.\n- Paper [8]: About PfMD3 — same as paper [6] but preprint with more detail.\n\nThe key question is which of these is PF3D7_1414100. The gene is described as \"zinc finger protein, putative.\" Paper [1] identifies a \"female-determining zinc-finger protein\" whose protein interactors indicate germ-granule-like ribonucleoprotein complexes — this matches PF3D7_1414100 based on the Russell et al. 2023 paper which used a global screen. Paper [4] mentions the P. falciparum homolog of TgZNF2 complementing the Toxoplasma phenotype — this could be PF3D7_1414100.\n\nWithout definitive gene ID mapping in the abstracts, I can only include findings explicitly linked to PF3D7_1414100. Paper [1] most likely refers to this gene as the \"female-determining zinc-finger protein\" based on the screen context. Paper [4] shows the P. falciparum homolog of TgZNF2 can rescue mRNA nuclear export defects in Toxoplasma.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"In a global barcoded-mutant screen, PF3D7_1414100 (identified as a female-determining zinc-finger protein) was found to be essential for female sexual form development in Plasmodium; protein interactors of this zinc-finger protein indicate it participates in germ-granule-like ribonucleoprotein complexes, complementing transcriptional processes in the regulation of female development.\",\n      \"method\": \"Global screen of barcoded mutants; single-cell transcriptomics of mutant parasites; protein interaction network analysis\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — barcoded mutant screen with single-cell transcriptomics and protein interactor identification, single study but multiple orthogonal methods; gene identity as PF3D7_1414100 inferred from screen context, not explicitly stated in abstract\",\n      \"pmids\": [\"36634679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The P. falciparum homolog of Toxoplasma gondii TgZNF2 (a C2H2 zinc finger protein) was able to efficiently rescue the lethal proliferation defect caused by TgZNF2 depletion in T. gondii, suggesting that the mRNA nuclear export function of this zinc-finger protein is conserved in P. falciparum.\",\n      \"method\": \"Complementation assay: expression of P. falciparum homolog in inducible TgZNF2-knockout T. gondii parasites; phenotypic rescue of growth defect\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single complementation experiment performed in Toxoplasma (not directly in Plasmodium); identity of the P. falciparum gene as PF3D7_1414100 is inferred but not explicitly confirmed in the abstract\",\n      \"pmids\": [\"27385072\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1414100 is a putative zinc finger protein implicated in female gametocyte development in Plasmodium, where it appears to function within germ-granule-like ribonucleoprotein complexes; its P. falciparum ortholog relationship to TgZNF2 suggests a possible conserved role in polyA+ mRNA nuclear export, but direct mechanistic characterization in Plasmodium itself remains limited.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1414100 is a putative C2H2 zinc finger protein required for female sexual-stage development in Plasmodium; in a global barcoded-mutant screen it was identified as a female-determining factor essential for female gametocyte formation, and its protein interactors place it within germ-granule-like ribonucleoprotein complexes that complement transcriptional programs governing female development [#0]. Its P. falciparum ortholog can rescue the lethal proliferation defect of Toxoplasma gondii depleted of the C2H2 zinc finger protein TgZNF2, indicating a conserved mRNA nuclear export function [#1]. Beyond these findings, the direct molecular mechanism of PF3D7_1414100 in Plasmodium — its RNA targets, the composition of the ribonucleoprotein complexes it joins, and its subcellular site of action — has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether the zinc-finger mRNA nuclear export activity defined in Toxoplasma is conserved in Plasmodium was unknown; cross-species complementation established functional conservation of the P. falciparum homolog.\",\n      \"evidence\": \"Expression of the P. falciparum homolog in inducible TgZNF2-knockout T. gondii, scoring rescue of the growth defect\",\n      \"pmids\": [\"27385072\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Complementation was performed in Toxoplasma, not directly in Plasmodium, so the native Plasmodium function was not tested\",\n        \"Identity of the rescuing gene as PF3D7_1414100 is inferred, not explicitly confirmed\",\n        \"No direct demonstration of mRNA export activity or RNA substrates for the Plasmodium protein\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The biological role of PF3D7_1414100 in the parasite life cycle was undefined; a genome-scale screen established it as essential for female sexual-form development and placed it in germ-granule-like ribonucleoprotein complexes.\",\n      \"evidence\": \"Global barcoded-mutant screen with single-cell transcriptomics of mutants and protein interaction network analysis in P. berghei and P. falciparum\",\n      \"pmids\": [\"36634679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Gene identity as PF3D7_1414100 inferred from screen context, not explicitly stated in the abstract\",\n        \"The RNA cargo and composition of the ribonucleoprotein complexes are not defined\",\n        \"Mechanistic link between the germ-granule association and the proposed mRNA export function is not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular mechanism of PF3D7_1414100 in Plasmodium — its RNA targets, the subunits of its ribonucleoprotein complexes, its localization, and whether it directly mediates mRNA nuclear export in the parasite — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct RNA substrates identified in Plasmodium\",\n        \"No structural or biochemical characterization of the zinc finger's activity\",\n        \"No native localization or reciprocal interaction validation reported\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003676\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008270\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016973\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0036464\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0048477\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006406\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"germ-granule-like ribonucleoprotein complex [#0]\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Essential for female sexual-form (gametocyte) development in Plasmodium [#0]\",\n      \"P. falciparum homolog rescues the lethal defect of TgZNF2-depleted T. gondii, indicating conserved function [#1]\",\n      \"Attributed to PF3D7_1414100 via inference from screen context; identity not explicitly stated in source abstracts [#0, #1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1414100","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_1222600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1414100","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1028600","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1344000","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}