{"gene":"PF3D7_0805300","run_date":"2026-09-11T10:06:41","timeline":{"discoveries":[{"year":2023,"finding":"PF3D7_0805300, a zinc-finger protein, was identified as a female-determining factor in Plasmodium berghei sexual development; its protein interactors indicate it participates in germ-granule-like ribonucleoprotein complexes that complement transcriptional regulation of female gametocyte determination.","method":"Global screen of barcoded mutants coupled with high-resolution single-cell transcriptomics of mutant parasites","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — barcode-screen + single-cell transcriptomics identify essentiality and interactors, but mechanistic dissection of the RNP complex is not fully resolved in this abstract; single study","pmids":["36634679"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"The P. falciparum homolog of TgZNF2 (annotated as a C2H2 zinc finger protein, corresponding to PF3D7_0805300) was able to functionally rescue the mRNA nuclear export defect caused by TgZNF2 depletion in Toxoplasma gondii, suggesting that the mRNA nuclear export function is conserved in P. falciparum.","method":"Complementation of inducible knockout (iKO-TgZNF2) T. gondii parasites with the P. falciparum homolog; polyA+ mRNA localization assay","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional rescue in a heterologous system (T. gondii) infers conservation but does not directly demonstrate the mechanism in P. falciparum; single lab, single complementation experiment","pmids":["27385072"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0805300 is a C2H2-type zinc finger protein essential for female gametocyte determination in P. falciparum, whose protein interactors implicate it in germ-granule-like ribonucleoprotein complexes; its functional conservation with the Toxoplasma TgZNF2 homolog further suggests a role in polyA+ mRNA nuclear export, though this has not been directly demonstrated in Plasmodium."},"narrative":{"mechanistic_narrative":"PF3D7_0805300 is a C2H2-type zinc finger protein that functions as a female-determining factor in Plasmodium berghei sexual development, acting through germ-granule-like ribonucleoprotein complexes that complement transcriptional regulation of female gametocyte determination [PMID:36634679]. Its protein interactors place it within RNP assemblies rather than assigning it a resolved catalytic or regulatory step, and the mechanistic detail of how this complex drives female commitment has not been dissected in the available corpus [PMID:36634679]. Beyond its role in female gametocyte determination, no direct mechanistic characterization of PF3D7_0805300 in P. falciparum has been established.","teleology":[{"year":2016,"claim":"Whether PF3D7_0805300 carries a conserved function was first addressed by asking if it could substitute for a mRNA nuclear export factor in a related apicomplexan, establishing possible functional conservation before its native role was known.","evidence":"Complementation of inducible TgZNF2-knockout Toxoplasma gondii with the P. falciparum homolog and a polyA+ mRNA localization assay","pmids":["27385072"],"confidence":"Low","gaps":["Rescue is in a heterologous T. gondii system and does not directly demonstrate an mRNA nuclear export function in P. falciparum","Single lab, single complementation experiment without reciprocal validation","No demonstration that PF3D7_0805300 binds RNA or the nuclear export machinery in Plasmodium"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"The native biological role of PF3D7_0805300 was resolved by showing it is required for female gametocyte determination, linking the protein to sexual-stage commitment and to germ-granule-like RNP complexes.","evidence":"Global barcoded-mutant screen coupled with high-resolution single-cell transcriptomics of mutant P. falciparum parasites, with interactor identification","pmids":["36634679"],"confidence":"Medium","gaps":["The composition and mechanism of the germ-granule-like RNP complex are not resolved","How PF3D7_0805300 mechanistically drives female determination (RNA targets, transcriptional vs post-transcriptional action) is unknown","Single study without independent replication"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether the mRNA nuclear export activity inferred from heterologous rescue operates natively in P. falciparum and how it connects, if at all, to the RNP-based control of female gametocyte determination.","evidence":"No direct mechanistic experiment in P. falciparum links the two lines of evidence","pmids":[],"confidence":"Low","gaps":["No direct demonstration of mRNA export or RNA-binding activity in P. falciparum","No structural model of the zinc finger domains in complex with RNA or partners","No identified RNA substrates or transcripts regulated by the protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["germ-granule-like ribonucleoprotein complex [#0]"],"partners":["UNSPECIFIED PROTEIN INTERACTORS WITHIN GERM-GRANULE-LIKE RNP COMPLEXES [#0]"],"other_free_text":["C2H2-type zinc finger protein required for female gametocyte determination in P. falciparum [#0]","P. falciparum homolog rescues the mRNA nuclear export defect of TgZNF2-depleted T. gondii, inferring conserved mRNA export function not directly shown in Plasmodium [#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":"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4043,"output_tokens":694,"usd":0.01127,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5236,"output_tokens":1627,"usd":0.033427,"stage2_stop_reason":"end_turn"},"total_usd":0.044697,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard","patch_2026_09_11":["species attribution corrected after review"]},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"PF3D7_0805300, a zinc-finger protein, was identified as a female-determining factor in Plasmodium falciparum sexual development; its protein interactors indicate it participates in germ-granule-like ribonucleoprotein complexes that complement transcriptional regulation of female gametocyte determination.\",\n      \"method\": \"Global screen of barcoded mutants coupled with high-resolution single-cell transcriptomics of mutant parasites\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — barcode-screen + single-cell transcriptomics identify essentiality and interactors, but mechanistic dissection of the RNP complex is not fully resolved in this abstract; single study\",\n      \"pmids\": [\"36634679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The P. falciparum homolog of TgZNF2 (annotated as a C2H2 zinc finger protein, corresponding to PF3D7_0805300) was able to functionally rescue the mRNA nuclear export defect caused by TgZNF2 depletion in Toxoplasma gondii, suggesting that the mRNA nuclear export function is conserved in P. falciparum.\",\n      \"method\": \"Complementation of inducible knockout (iKO-TgZNF2) T. gondii parasites with the P. falciparum homolog; polyA+ mRNA localization assay\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional rescue in a heterologous system (T. gondii) infers conservation but does not directly demonstrate the mechanism in P. falciparum; single lab, single complementation experiment\",\n      \"pmids\": [\"27385072\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0805300 is a C2H2-type zinc finger protein essential for female gametocyte determination in P. falciparum, whose protein interactors implicate it in germ-granule-like ribonucleoprotein complexes; its functional conservation with the Toxoplasma TgZNF2 homolog further suggests a role in polyA+ mRNA nuclear export, though this has not been directly demonstrated in Plasmodium.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0805300 is a C2H2-type zinc finger protein that functions as a female-determining factor in Plasmodium falciparum sexual development, acting through germ-granule-like ribonucleoprotein complexes that complement transcriptional regulation of female gametocyte determination [#0]. Its protein interactors place it within RNP assemblies rather than assigning it a resolved catalytic or regulatory step, and the mechanistic detail of how this complex drives female commitment has not been dissected in the available corpus [#0]. Beyond its role in female gametocyte determination, no direct mechanistic characterization of PF3D7_0805300 in P. falciparum has been established.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether PF3D7_0805300 carries a conserved function was first addressed by asking if it could substitute for a mRNA nuclear export factor in a related apicomplexan, establishing possible functional conservation before its native role was known.\",\n      \"evidence\": \"Complementation of inducible TgZNF2-knockout Toxoplasma gondii with the P. falciparum homolog and a polyA+ mRNA localization assay\",\n      \"pmids\": [\"27385072\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Rescue is in a heterologous T. gondii system and does not directly demonstrate an mRNA nuclear export function in P. falciparum\",\n        \"Single lab, single complementation experiment without reciprocal validation\",\n        \"No demonstration that PF3D7_0805300 binds RNA or the nuclear export machinery in Plasmodium\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The native biological role of PF3D7_0805300 was resolved by showing it is required for female gametocyte determination, linking the protein to sexual-stage commitment and to germ-granule-like RNP complexes.\",\n      \"evidence\": \"Global barcoded-mutant screen coupled with high-resolution single-cell transcriptomics of mutant P. falciparum parasites, with interactor identification\",\n      \"pmids\": [\"36634679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The composition and mechanism of the germ-granule-like RNP complex are not resolved\",\n        \"How PF3D7_0805300 mechanistically drives female determination (RNA targets, transcriptional vs post-transcriptional action) is unknown\",\n        \"Single study without independent replication\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether the mRNA nuclear export activity inferred from heterologous rescue operates natively in P. falciparum and how it connects, if at all, to the RNP-based control of female gametocyte determination.\",\n      \"evidence\": \"No direct mechanistic experiment in P. falciparum links the two lines of evidence\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct demonstration of mRNA export or RNA-binding activity in P. falciparum\",\n        \"No structural model of the zinc finger domains in complex with RNA or partners\",\n        \"No identified RNA substrates or transcripts regulated by the protein\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\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\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0036464\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0060968\", \"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      \"unspecified protein interactors within germ-granule-like RNP complexes [#0]\"\n    ],\n    \"other_free_text\": [\n      \"C2H2-type zinc finger protein required for female gametocyte determination in P. falciparum [#0]\",\n      \"P. falciparum homolog rescues the mRNA nuclear export defect of TgZNF2-depleted T. gondii, inferring conserved mRNA export function not directly shown in Plasmodium [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0805300","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1225300","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0113900","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}