{"gene":"PF3D7_1328200","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2003,"finding":"Computational sequence analysis identified partial BRCA2 homologues in two Plasmodium species containing BRC repeat motifs; using the crystal structure of the human BRC4-RAD51 complex to define interaction sequence fingerprints, it was predicted that the Plasmodium BRC repeats should be capable of interacting with RAD51 orthologues, suggesting conservation of the BRCA2-RAD51 homologous recombination pathway.","method":"Comparative sequence analysis and computational fingerprint mapping using the crystal structure of human BRC4-RAD51 complex","journal":"DNA repair","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/structural inference only, no direct experiment performed on the Plasmodium protein","pmids":["12967658"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"P. berghei BRCA2 (PbBrca2, the ortholog of PF3D7_1328200) BRC repeats interact with PbRad51 in a mammalian two-hybrid assay, establishing a direct physical interaction between BRCA2 and Rad51 in Plasmodium.","method":"Mammalian two-hybrid assay","journal":"Parasites & vectors","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct protein-protein interaction established by two-hybrid, single lab, single method","pmids":["35804459"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"Knockout of P. berghei BRCA2 (PbBrca2) caused reduced parasitemia with increased ring stage and decreased trophozoite stage counts, reduced gametocytemia, altered female gametocyte ratio, reduced oocyst number, impaired ookinete development, and complete failure of sporogony progression (as shown by transmission electron microscopy), demonstrating that BRCA2 is required for normal parasite development across multiple life cycle stages and especially for meiotic homologous recombination during sporogony.","method":"Genetic knockout (loss-of-function), parasite proliferation and differentiation assays in mice and mosquitoes, transmission electron microscopy","journal":"Parasites & vectors","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotypes across multiple life stages, multiple readouts, single lab","pmids":["35804459"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"Plasmodium BRCA2 (PF3D7_1328200 and its P. berghei ortholog) contains conserved BRC repeat motifs that directly interact with Rad51, implicating it in homologous recombination; functional knockout in P. berghei demonstrates it is required for normal development across blood, gametocyte, and mosquito stages, and is essential for meiotic recombination during sporogony."},"narrative":{"mechanistic_narrative":"PF3D7_1328200 (BRCA2) is a Plasmodium homologue of BRCA2 implicated in homologous recombination through its conserved BRC repeat motifs, which were computationally predicted to interact with RAD51 orthologues based on the human BRC4-RAD51 interaction fingerprint [PMID:12967658]. In the rodent malaria parasite P. berghei, the BRC repeats of the ortholog directly bind Rad51 in a mammalian two-hybrid assay, confirming a physical BRCA2-Rad51 interaction in Plasmodium [PMID:35804459]. Genetic knockout of P. berghei BRCA2 impairs parasite development across the life cycle — reducing parasitemia and shifting stage distribution, lowering gametocytemia and altering female gametocyte ratio, reducing oocyst numbers and ookinete development, and causing complete failure of sporogony — establishing that BRCA2 is required for normal blood-, gametocyte-, and mosquito-stage development and is especially critical for meiotic recombination during sporogony [PMID:35804459]. Beyond the BRC-repeat/Rad51 interaction and the knockout phenotypes, no further biochemical or structural characterization of PF3D7_1328200 has been reported in the available corpus.","teleology":[{"year":2003,"claim":"Whether Plasmodium possesses a functional BRCA2-RAD51 homologous recombination pathway was unknown; sequence analysis addressed whether the parasite encodes a BRCA2 capable of RAD51 engagement.","evidence":"Comparative sequence analysis and computational fingerprint mapping against the human BRC4-RAD51 crystal structure","pmids":["12967658"],"confidence":"Low","gaps":["Purely computational inference — no direct experiment on the Plasmodium protein","Interaction with RAD51 predicted but not demonstrated","No functional role established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"The predicted BRCA2-Rad51 interaction was tested directly, establishing that Plasmodium BRCA2 BRC repeats physically bind Rad51.","evidence":"Mammalian two-hybrid assay with P. berghei BRCA2 BRC repeats and PbRad51","pmids":["35804459"],"confidence":"Medium","gaps":["Single method, single lab — no reciprocal or in-parasite interaction validation","Binding affinity and stoichiometry not quantified","Shown for the P. berghei ortholog, not PF3D7_1328200 itself"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"The functional requirement for BRCA2 across the parasite life cycle was unresolved; knockout defined its developmental roles and pinpointed sporogony as the most affected process.","evidence":"Genetic knockout with proliferation/differentiation assays in mice and mosquitoes plus transmission electron microscopy","pmids":["35804459"],"confidence":"Medium","gaps":["Complementation/rescue not reported to confirm phenotype specificity","Whether sporogony failure reflects a direct meiotic HR defect at the molecular level not shown","Established in P. berghei; not directly demonstrated for PF3D7_1328200"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct biochemical role of PF3D7_1328200 in homologous recombination and its molecular contribution to meiotic recombination during sporogony remain uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct functional data on the P. falciparum protein PF3D7_1328200 itself","No structural model of the Plasmodium BRCA2-Rad51 complex","Mechanism by which BRCA2 loss blocks meiotic recombination not resolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RAD51 / PBRAD51 (DIRECT INTERACTION VIA BRC REPEATS)"],"other_free_text":["Contains conserved BRC repeat motifs predicted from the human BRC4-RAD51 interaction fingerprint [#0]","P. berghei BRCA2 knockout impairs blood-stage proliferation, gametocytogenesis, ookinete/oocyst development, and abolishes sporogony [#2]","Findings on the ortholog are in P. berghei; direct characterization of the P. falciparum gene PF3D7_1328200 is absent from the corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12967658","id":"PMC_12967658","title":"Sequence fingerprints in BRCA2 and RAD51: implications for DNA repair and cancer.","date":"2003","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/12967658","citation_count":100,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["BRCA2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35804459","id":"PMC_35804459","title":"Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes.","date":"2022","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/35804459","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["BRCA2","PbBRCA2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4110,"output_tokens":890,"usd":0.01284,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5613,"output_tokens":1927,"usd":0.03812,"stage2_stop_reason":"end_turn"},"total_usd":0.05096,"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\": 2003,\n      \"finding\": \"Computational sequence analysis identified partial BRCA2 homologues in two Plasmodium species containing BRC repeat motifs; using the crystal structure of the human BRC4-RAD51 complex to define interaction sequence fingerprints, it was predicted that the Plasmodium BRC repeats should be capable of interacting with RAD51 orthologues, suggesting conservation of the BRCA2-RAD51 homologous recombination pathway.\",\n      \"method\": \"Comparative sequence analysis and computational fingerprint mapping using the crystal structure of human BRC4-RAD51 complex\",\n      \"journal\": \"DNA repair\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/structural inference only, no direct experiment performed on the Plasmodium protein\",\n      \"pmids\": [\"12967658\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"P. berghei BRCA2 (PbBrca2, the ortholog of PF3D7_1328200) BRC repeats interact with PbRad51 in a mammalian two-hybrid assay, establishing a direct physical interaction between BRCA2 and Rad51 in Plasmodium.\",\n      \"method\": \"Mammalian two-hybrid assay\",\n      \"journal\": \"Parasites & vectors\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct protein-protein interaction established by two-hybrid, single lab, single method\",\n      \"pmids\": [\"35804459\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Knockout of P. berghei BRCA2 (PbBrca2) caused reduced parasitemia with increased ring stage and decreased trophozoite stage counts, reduced gametocytemia, altered female gametocyte ratio, reduced oocyst number, impaired ookinete development, and complete failure of sporogony progression (as shown by transmission electron microscopy), demonstrating that BRCA2 is required for normal parasite development across multiple life cycle stages and especially for meiotic homologous recombination during sporogony.\",\n      \"method\": \"Genetic knockout (loss-of-function), parasite proliferation and differentiation assays in mice and mosquitoes, transmission electron microscopy\",\n      \"journal\": \"Parasites & vectors\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotypes across multiple life stages, multiple readouts, single lab\",\n      \"pmids\": [\"35804459\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"Plasmodium BRCA2 (PF3D7_1328200 and its P. berghei ortholog) contains conserved BRC repeat motifs that directly interact with Rad51, implicating it in homologous recombination; functional knockout in P. berghei demonstrates it is required for normal development across blood, gametocyte, and mosquito stages, and is essential for meiotic recombination during sporogony.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1328200 (BRCA2) is a Plasmodium homologue of BRCA2 implicated in homologous recombination through its conserved BRC repeat motifs, which were computationally predicted to interact with RAD51 orthologues based on the human BRC4-RAD51 interaction fingerprint [#0]. In the rodent malaria parasite P. berghei, the BRC repeats of the ortholog directly bind Rad51 in a mammalian two-hybrid assay, confirming a physical BRCA2-Rad51 interaction in Plasmodium [#1]. Genetic knockout of P. berghei BRCA2 impairs parasite development across the life cycle — reducing parasitemia and shifting stage distribution, lowering gametocytemia and altering female gametocyte ratio, reducing oocyst numbers and ookinete development, and causing complete failure of sporogony — establishing that BRCA2 is required for normal blood-, gametocyte-, and mosquito-stage development and is especially critical for meiotic recombination during sporogony [#2]. Beyond the BRC-repeat/Rad51 interaction and the knockout phenotypes, no further biochemical or structural characterization of PF3D7_1328200 has been reported in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Whether Plasmodium possesses a functional BRCA2-RAD51 homologous recombination pathway was unknown; sequence analysis addressed whether the parasite encodes a BRCA2 capable of RAD51 engagement.\",\n      \"evidence\": \"Comparative sequence analysis and computational fingerprint mapping against the human BRC4-RAD51 crystal structure\",\n      \"pmids\": [\"12967658\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational inference \\u2014 no direct experiment on the Plasmodium protein\",\n        \"Interaction with RAD51 predicted but not demonstrated\",\n        \"No functional role established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The predicted BRCA2-Rad51 interaction was tested directly, establishing that Plasmodium BRCA2 BRC repeats physically bind Rad51.\",\n      \"evidence\": \"Mammalian two-hybrid assay with P. berghei BRCA2 BRC repeats and PbRad51\",\n      \"pmids\": [\"35804459\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method, single lab \\u2014 no reciprocal or in-parasite interaction validation\",\n        \"Binding affinity and stoichiometry not quantified\",\n        \"Shown for the P. berghei ortholog, not PF3D7_1328200 itself\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The functional requirement for BRCA2 across the parasite life cycle was unresolved; knockout defined its developmental roles and pinpointed sporogony as the most affected process.\",\n      \"evidence\": \"Genetic knockout with proliferation/differentiation assays in mice and mosquitoes plus transmission electron microscopy\",\n      \"pmids\": [\"35804459\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Complementation/rescue not reported to confirm phenotype specificity\",\n        \"Whether sporogony failure reflects a direct meiotic HR defect at the molecular level not shown\",\n        \"Established in P. berghei; not directly demonstrated for PF3D7_1328200\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical role of PF3D7_1328200 in homologous recombination and its molecular contribution to meiotic recombination during sporogony remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct functional data on the P. falciparum protein PF3D7_1328200 itself\",\n        \"No structural model of the Plasmodium BRCA2-Rad51 complex\",\n        \"Mechanism by which BRCA2 loss blocks meiotic recombination not resolved\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008094\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035825\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0007131\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Rad51 / PbRad51 (direct interaction via BRC repeats)\"\n    ],\n    \"other_free_text\": [\n      \"Contains conserved BRC repeat motifs predicted from the human BRC4-RAD51 interaction fingerprint [#0]\",\n      \"P. berghei BRCA2 knockout impairs blood-stage proliferation, gametocytogenesis, ookinete/oocyst development, and abolishes sporogony [#2]\",\n      \"Findings on the ortholog are in P. berghei; direct characterization of the P. falciparum gene PF3D7_1328200 is absent from the corpus\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1328200","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_0816800, PF3D7_1107400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1328200","name":null,"product":"BRCA2 protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1343400","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1200400","name":null,"product":"BRCA2 protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}