{"gene":"PF3D7_1011700","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2016,"finding":"RAD23 (PF3D7_1011700) is among 18 DNA repair genes found to carry point mutations in two P. falciparum mutator strains (Dd2 and W2) that fail to induce DNA repair upon MMS-induced DNA damage, placing RAD23 within the excision repair system transcriptionally regulated in response to genotoxic stress.","method":"Genome-wide transcriptional profiling after MMS treatment combined with genome sequencing of mutator strains to identify point mutations in DNA repair genes","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional/genomic survey in a single study; no direct functional assay specific to RAD23; RAD23 is one of 18 genes listed without individual mechanistic dissection","pmids":["27033103"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"Dd2"},{"species":"Plasmodium falciparum","strain":"W2"}]},{"year":2025,"finding":"RAD23 (PF3D7_1011700) is identified as a component of the P. falciparum ubiquitin-proteasome system (UPS) alongside Dsk2 and Ddi1, implicated in the unfolded protein response under stress; however, the paper's experimental work focuses on PfDdi1, not RAD23 directly.","method":"Computational docking and molecular dynamics simulation (study of PfDdi1, with RAD23 mentioned as a UPS component)","journal":"Cell biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — RAD23 is mentioned contextually as a UPS member; no direct experiment was performed on RAD23 itself in this study","pmids":["40113723"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1011700 (RAD23) is a putative DNA repair protein in P. falciparum implicated in the excision repair response to genotoxic stress and proposed as a component of the ubiquitin-proteasome system alongside Dsk2 and Ddi1, but no direct biochemical or structural experiments have been performed specifically on this protein to define its mechanism of action."},"narrative":{"mechanistic_narrative":"PF3D7_1011700 (RAD23) is a putative P. falciparum DNA repair protein placed within the parasite's excision repair response to genotoxic stress: in the mutator strains Dd2 and W2, which fail to mount a DNA repair transcriptional response after MMS-induced damage, RAD23 was one of 18 DNA repair genes found to carry point mutations [PMID:27033103]. It has additionally been named as a component of the parasite ubiquitin-proteasome system alongside Dsk2 and Ddi1, linked to the unfolded protein response under stress [PMID:40113723]. No direct biochemical, structural, or functional experiment has been performed on PF3D7_1011700 itself in the available corpus; both findings mention it as a member of a gene set or complex rather than characterizing its mechanism, so beyond these associations its molecular activity, partners, and role are uncharacterized.","teleology":[{"year":2016,"claim":"To locate RAD23 within the parasite's genotoxic stress response, transcriptional and genomic profiling of MMS-treated mutator strains tested which DNA repair genes are compromised when repair induction fails.","evidence":"Genome-wide transcriptional profiling after MMS treatment plus genome sequencing of Dd2 and W2 mutator strains","pmids":["27033103"],"confidence":"Low","gaps":["RAD23 is one of 18 listed genes with no individual functional assay specific to it","point mutations were not shown to alter RAD23 function or repair activity","no direct evidence that RAD23 participates in excision repair mechanistically"],"attribution":[{"species":"Plasmodium falciparum","strain":"Dd2"},{"species":"Plasmodium falciparum","strain":"W2"}]},{"year":2025,"claim":"To situate RAD23 in the parasite proteostasis network, a study of PfDdi1 named RAD23 as a co-member of the ubiquitin-proteasome system tied to the unfolded protein response.","evidence":"Computational docking and molecular dynamics simulation focused on PfDdi1, with RAD23 cited contextually as a UPS component alongside Dsk2 and Ddi1","pmids":["40113723"],"confidence":"Low","gaps":["no experiment was performed on RAD23 itself in this study","physical interaction of RAD23 with Dsk2, Ddi1, or the proteasome not demonstrated","role of RAD23 in the unfolded protein response not directly tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_1011700 has any direct biochemical activity, binding partners, or defined role in either DNA repair or the ubiquitin-proteasome system remains entirely uncharacterized.","evidence":"No direct functional, biochemical, or structural experiment on RAD23 exists in the corpus","pmids":[],"confidence":"Low","gaps":["no direct enzymatic or binding assay on RAD23","no structural model specific to RAD23","no genetic knockout or complementation defining its cellular role"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["DSK2 (CONTEXTUAL UPS CO-MEMBER, NO DIRECT INTERACTION SHOWN) [#1]","DDI1 (CONTEXTUAL UPS CO-MEMBER, NO DIRECT INTERACTION SHOWN) [#1]"],"other_free_text":["RAD23 (PF3D7_1011700) appears only as a member of a gene set or complex in the corpus; no direct experiment has been performed on this protein itself.","Named among 18 DNA repair genes carrying point mutations in MMS-response-deficient mutator strains Dd2 and W2 [#0].","Cited as a ubiquitin-proteasome system component alongside Dsk2 and Ddi1, but the associated study's experiments concern PfDdi1, not RAD23 [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27033103","id":"PMC_27033103","title":"DNA damage regulation and its role in drug-related phenotypes in the malaria parasites.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27033103","citation_count":56,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15948708","id":"PMC_15948708","title":"DNA-[adenine] methylation in lower eukaryotes.","date":"2005","source":"Biochemistry. Biokhimiia","url":"https://pubmed.ncbi.nlm.nih.gov/15948708","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2892060","id":"PMC_2892060","title":"From Laveran's discovery to DNA probes: new trends in diagnosis of malaria.","date":"1987","source":"Lancet (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/2892060","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40113723","id":"PMC_40113723","title":"Computational Analysis of Plasmodium falciparum DNA Damage Inducible Protein 1 (PfDdi1): Insights into Binding of Artemisinin and its Derivatives and Implications for Antimalarial Drug Design.","date":"2025","source":"Cell biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/40113723","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD23"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4381,"output_tokens":682,"usd":0.011687,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5293,"output_tokens":1610,"usd":0.033357,"stage2_stop_reason":"end_turn"},"total_usd":0.045044,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"RAD23 (PF3D7_1011700) is among 18 DNA repair genes found to carry point mutations in two P. falciparum mutator strains (Dd2 and W2) that fail to induce DNA repair upon MMS-induced DNA damage, placing RAD23 within the excision repair system transcriptionally regulated in response to genotoxic stress.\",\n      \"method\": \"Genome-wide transcriptional profiling after MMS treatment combined with genome sequencing of mutator strains to identify point mutations in DNA repair genes\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional/genomic survey in a single study; no direct functional assay specific to RAD23; RAD23 is one of 18 genes listed without individual mechanistic dissection\",\n      \"pmids\": [\"27033103\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"W2\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RAD23 (PF3D7_1011700) is identified as a component of the P. falciparum ubiquitin-proteasome system (UPS) alongside Dsk2 and Ddi1, implicated in the unfolded protein response under stress; however, the paper's experimental work focuses on PfDdi1, not RAD23 directly.\",\n      \"method\": \"Computational docking and molecular dynamics simulation (study of PfDdi1, with RAD23 mentioned as a UPS component)\",\n      \"journal\": \"Cell biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — RAD23 is mentioned contextually as a UPS member; no direct experiment was performed on RAD23 itself in this study\",\n      \"pmids\": [\"40113723\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1011700 (RAD23) is a putative DNA repair protein in P. falciparum implicated in the excision repair response to genotoxic stress and proposed as a component of the ubiquitin-proteasome system alongside Dsk2 and Ddi1, but no direct biochemical or structural experiments have been performed specifically on this protein to define its mechanism of action.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1011700 (RAD23) is a putative P. falciparum DNA repair protein placed within the parasite's excision repair response to genotoxic stress: in the mutator strains Dd2 and W2, which fail to mount a DNA repair transcriptional response after MMS-induced damage, RAD23 was one of 18 DNA repair genes found to carry point mutations [#0]. It has additionally been named as a component of the parasite ubiquitin-proteasome system alongside Dsk2 and Ddi1, linked to the unfolded protein response under stress [#1]. No direct biochemical, structural, or functional experiment has been performed on PF3D7_1011700 itself in the available corpus; both findings mention it as a member of a gene set or complex rather than characterizing its mechanism, so beyond these associations its molecular activity, partners, and role are uncharacterized.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"To locate RAD23 within the parasite's genotoxic stress response, transcriptional and genomic profiling of MMS-treated mutator strains tested which DNA repair genes are compromised when repair induction fails.\",\n      \"evidence\": \"Genome-wide transcriptional profiling after MMS treatment plus genome sequencing of Dd2 and W2 mutator strains\",\n      \"pmids\": [\"27033103\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"RAD23 is one of 18 listed genes with no individual functional assay specific to it\",\n        \"point mutations were not shown to alter RAD23 function or repair activity\",\n        \"no direct evidence that RAD23 participates in excision repair mechanistically\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"W2\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To situate RAD23 in the parasite proteostasis network, a study of PfDdi1 named RAD23 as a co-member of the ubiquitin-proteasome system tied to the unfolded protein response.\",\n      \"evidence\": \"Computational docking and molecular dynamics simulation focused on PfDdi1, with RAD23 cited contextually as a UPS component alongside Dsk2 and Ddi1\",\n      \"pmids\": [\"40113723\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no experiment was performed on RAD23 itself in this study\",\n        \"physical interaction of RAD23 with Dsk2, Ddi1, or the proteasome not demonstrated\",\n        \"role of RAD23 in the unfolded protein response not directly tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1011700 has any direct biochemical activity, binding partners, or defined role in either DNA repair or the ubiquitin-proteasome system remains entirely uncharacterized.\",\n      \"evidence\": \"No direct functional, biochemical, or structural experiment on RAD23 exists in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no direct enzymatic or binding assay on RAD23\",\n        \"no structural model specific to RAD23\",\n        \"no genetic knockout or complementation defining its cellular role\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006281\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0043161\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Dsk2 (contextual UPS co-member, no direct interaction shown) [#1]\", \"Ddi1 (contextual UPS co-member, no direct interaction shown) [#1]\"],\n    \"other_free_text\": [\n      \"RAD23 (PF3D7_1011700) appears only as a member of a gene set or complex in the corpus; no direct experiment has been performed on this protein itself.\",\n      \"Named among 18 DNA repair genes carrying point mutations in MMS-response-deficient mutator strains Dd2 and W2 [#0].\",\n      \"Cited as a ubiquitin-proteasome system component alongside Dsk2 and Ddi1, but the associated study's experiments concern PfDdi1, not RAD23 [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1011700","name":null,"product":"DNA repair protein RAD23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1210100","name":null,"product":"DNA repair protein RAD23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0811500","name":null,"product":"DNA repair protein RAD23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAD23","evaluation":null}