{"gene":"PF3D7_1458500","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2022,"finding":"In P. berghei, SAS4 (PF3D7_1458500 ortholog) localizes to basal bodies and forms a distinct subdomain (a SAS4-toroid in the lumen of the microtubule wall) within the basal body structure, surrounding centrin and SAS6 at the proximal and central cores. Basal bodies are de novo assembled in a SAS4-dependent manner from a deuterosome-like structure.","method":"Ultrastructure expansion microscopy (U-ExM) and Pan-ExM with 3D reconstruction and protein localization in P. berghei","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by U-ExM/Pan-ExM with 3D structural resolution and functional dependency shown; single lab but multiple orthogonal imaging methods","pmids":["35077503"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"In P. berghei, SAS4 co-localizes and associates with the basal body component kinesin-8B but does not associate with the kinetochore protein NDC80, establishing that SAS4 is part of the basal body and outer centriolar MTOC in the cytoplasm, not the intranuclear mitotic MTOC.","method":"Fluorescence co-localization and genetic association studies in P. berghei male gametocytes","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-localization with binding partner and negative result for NDC80 association; single lab, two orthogonal approaches (co-localization + genetic)","pmids":["35550346"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"Deletion of the SAS4 gene in P. berghei produced no phenotype for male gamete formation or parasite transmission, indicating SAS4 is dispensable for these processes.","method":"Gene deletion (knockout) with phenotypic readout of male gamete formation and mosquito transmission","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean gene knockout with defined cellular and transmission phenotype readout; single lab","pmids":["35550346"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1458500 (SAS4) localizes to basal bodies in Plasmodium male gametocytes, forming a toroid subdomain surrounding centrin and SAS6 within the microtubule wall lumen, and associates with the basal body component kinesin-8B but not with the kinetochore protein NDC80; despite its structural role in basal body organization, deletion of SAS4 in P. berghei has no detectable effect on male gamete formation or parasite transmission."},"narrative":{"mechanistic_narrative":"PF3D7_1458500 (SAS4) is a basal body component of the outer, cytoplasmic centriolar microtubule-organizing center in Plasmodium male gametocytes, where it contributes to de novo basal body assembly [PMID:35077503]. In P. berghei, SAS4 occupies a distinct structural subdomain, forming a toroid within the lumen of the basal body microtubule wall that surrounds centrin and SAS6 at the proximal and central cores, and basal bodies assemble from a deuterosome-like precursor in a SAS4-dependent manner [PMID:35077503]. SAS4 co-localizes and associates with the basal body kinesin-8B but not with the kinetochore protein NDC80, placing it at the cytoplasmic centriolar MTOC rather than the intranuclear mitotic MTOC [PMID:35550346]. Despite this structural role, deletion of SAS4 in P. berghei produces no detectable defect in male gamete formation or mosquito transmission, indicating it is dispensable for these processes [PMID:35550346]. Beyond these findings in the P. berghei ortholog, no further mechanistic detail for PF3D7_1458500 has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"To resolve where SAS4 sits within the parasite MTOC architecture, its subcellular position was mapped, establishing it as a distinct structural subdomain of the basal body required for de novo basal body assembly.","evidence":"Ultrastructure expansion microscopy (U-ExM) and Pan-ExM with 3D reconstruction and protein localization in P. berghei","pmids":["35077503"],"confidence":"Medium","gaps":["The molecular composition and binding partners forming the SAS4-toroid are not defined","How SAS4 mediates de novo basal body assembly from the deuterosome-like structure is not resolved","Findings rest on the P. berghei ortholog; direct validation in P. falciparum is absent"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"To determine which MTOC compartment SAS4 belongs to, its association with candidate partners was tested, distinguishing the cytoplasmic centriolar MTOC from the intranuclear mitotic MTOC.","evidence":"Fluorescence co-localization and genetic association studies in P. berghei male gametocytes","pmids":["35550346"],"confidence":"Medium","gaps":["The kinesin-8B association is shown by co-localization, not direct biochemical binding or reciprocal validation","Whether SAS4 functionally requires kinesin-8B is not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"To test whether SAS4's structural role is functionally required, the gene was deleted, showing it is dispensable for male gamete formation and transmission despite its basal body localization.","evidence":"Gene deletion (knockout) with phenotypic readout of male gamete formation and mosquito transmission","pmids":["35550346"],"confidence":"Medium","gaps":["The absence of phenotype leaves the physiological function of the SAS4-toroid unexplained","Possible redundancy with other basal body components was not tested","No phenotypic assay beyond gamete formation and transmission was examined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The molecular function of SAS4 and the physiological consequence of its basal body toroid remain unresolved, given that its structural presence is not matched by any deletion phenotype.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical activity or direct interaction partner has been defined for SAS4","The reason a structurally organized component is dispensable is unexplained","No data on the P. falciparum gene itself as opposed to the P. berghei ortholog"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["KINESIN-8B (CO-LOCALIZATION/ASSOCIATION, P. BERGHEI)"],"other_free_text":["Forms a toroid subdomain within the lumen of the basal body microtubule wall, surrounding centrin and SAS6 [#0]","Required for de novo basal body assembly from a deuterosome-like structure [#0]","Does not associate with the kinetochore protein NDC80; part of the cytoplasmic centriolar MTOC rather than the intranuclear mitotic MTOC [#1]","Dispensable for male gamete formation and mosquito transmission in P. berghei [#2]","All findings derive from the P. berghei ortholog of PF3D7_1458500"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"35077503","id":"PMC_35077503","title":"Expansion microscopy of Plasmodium gametocytes reveals the molecular architecture of a bipartite microtubule organisation centre coordinating mitosis with axoneme assembly.","date":"2022","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/35077503","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAS4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35550346","id":"PMC_35550346","title":"Plasmodium SAS4: basal body component of male cell which is dispensable for parasite transmission.","date":"2022","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/35550346","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAS4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3854,"output_tokens":877,"usd":0.012358,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5575,"output_tokens":1923,"usd":0.037975,"stage2_stop_reason":"end_turn"},"total_usd":0.050333,"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\": 2022,\n      \"finding\": \"In P. berghei, SAS4 (PF3D7_1458500 ortholog) localizes to basal bodies and forms a distinct subdomain (a SAS4-toroid in the lumen of the microtubule wall) within the basal body structure, surrounding centrin and SAS6 at the proximal and central cores. Basal bodies are de novo assembled in a SAS4-dependent manner from a deuterosome-like structure.\",\n      \"method\": \"Ultrastructure expansion microscopy (U-ExM) and Pan-ExM with 3D reconstruction and protein localization in P. berghei\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by U-ExM/Pan-ExM with 3D structural resolution and functional dependency shown; single lab but multiple orthogonal imaging methods\",\n      \"pmids\": [\"35077503\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. berghei, SAS4 co-localizes and associates with the basal body component kinesin-8B but does not associate with the kinetochore protein NDC80, establishing that SAS4 is part of the basal body and outer centriolar MTOC in the cytoplasm, not the intranuclear mitotic MTOC.\",\n      \"method\": \"Fluorescence co-localization and genetic association studies in P. berghei male gametocytes\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-localization with binding partner and negative result for NDC80 association; single lab, two orthogonal approaches (co-localization + genetic)\",\n      \"pmids\": [\"35550346\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Deletion of the SAS4 gene in P. berghei produced no phenotype for male gamete formation or parasite transmission, indicating SAS4 is dispensable for these processes.\",\n      \"method\": \"Gene deletion (knockout) with phenotypic readout of male gamete formation and mosquito transmission\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean gene knockout with defined cellular and transmission phenotype readout; single lab\",\n      \"pmids\": [\"35550346\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1458500 (SAS4) localizes to basal bodies in Plasmodium male gametocytes, forming a toroid subdomain surrounding centrin and SAS6 within the microtubule wall lumen, and associates with the basal body component kinesin-8B but not with the kinetochore protein NDC80; despite its structural role in basal body organization, deletion of SAS4 in P. berghei has no detectable effect on male gamete formation or parasite transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1458500 (SAS4) is a basal body component of the outer, cytoplasmic centriolar microtubule-organizing center in Plasmodium male gametocytes, where it contributes to de novo basal body assembly [#0]. In P. berghei, SAS4 occupies a distinct structural subdomain, forming a toroid within the lumen of the basal body microtubule wall that surrounds centrin and SAS6 at the proximal and central cores, and basal bodies assemble from a deuterosome-like precursor in a SAS4-dependent manner [#0]. SAS4 co-localizes and associates with the basal body kinesin-8B but not with the kinetochore protein NDC80, placing it at the cytoplasmic centriolar MTOC rather than the intranuclear mitotic MTOC [#1]. Despite this structural role, deletion of SAS4 in P. berghei produces no detectable defect in male gamete formation or mosquito transmission, indicating it is dispensable for these processes [#2]. Beyond these findings in the P. berghei ortholog, no further mechanistic detail for PF3D7_1458500 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"To resolve where SAS4 sits within the parasite MTOC architecture, its subcellular position was mapped, establishing it as a distinct structural subdomain of the basal body required for de novo basal body assembly.\",\n      \"evidence\": \"Ultrastructure expansion microscopy (U-ExM) and Pan-ExM with 3D reconstruction and protein localization in P. berghei\",\n      \"pmids\": [\"35077503\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular composition and binding partners forming the SAS4-toroid are not defined\",\n        \"How SAS4 mediates de novo basal body assembly from the deuterosome-like structure is not resolved\",\n        \"Findings rest on the P. berghei ortholog; direct validation in P. falciparum is absent\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To determine which MTOC compartment SAS4 belongs to, its association with candidate partners was tested, distinguishing the cytoplasmic centriolar MTOC from the intranuclear mitotic MTOC.\",\n      \"evidence\": \"Fluorescence co-localization and genetic association studies in P. berghei male gametocytes\",\n      \"pmids\": [\"35550346\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The kinesin-8B association is shown by co-localization, not direct biochemical binding or reciprocal validation\",\n        \"Whether SAS4 functionally requires kinesin-8B is not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To test whether SAS4's structural role is functionally required, the gene was deleted, showing it is dispensable for male gamete formation and transmission despite its basal body localization.\",\n      \"evidence\": \"Gene deletion (knockout) with phenotypic readout of male gamete formation and mosquito transmission\",\n      \"pmids\": [\"35550346\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The absence of phenotype leaves the physiological function of the SAS4-toroid unexplained\",\n        \"Possible redundancy with other basal body components was not tested\",\n        \"No phenotypic assay beyond gamete formation and transmission was examined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of SAS4 and the physiological consequence of its basal body toroid remain unresolved, given that its structural presence is not matched by any deletion phenotype.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical activity or direct interaction partner has been defined for SAS4\",\n        \"The reason a structurally organized component is dispensable is unexplained\",\n        \"No data on the P. falciparum gene itself as opposed to the P. berghei ortholog\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0036064\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0098534\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"kinesin-8B (co-localization/association, P. berghei)\"],\n    \"other_free_text\": [\n      \"Forms a toroid subdomain within the lumen of the basal body microtubule wall, surrounding centrin and SAS6 [#0]\",\n      \"Required for de novo basal body assembly from a deuterosome-like structure [#0]\",\n      \"Does not associate with the kinetochore protein NDC80; part of the cytoplasmic centriolar MTOC rather than the intranuclear mitotic MTOC [#1]\",\n      \"Dispensable for male gamete formation and mosquito transmission in P. berghei [#2]\",\n      \"All findings derive from the P. berghei ortholog of PF3D7_1458500\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1458500","name":null,"product":"spindle assembly abnormal protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1322200","name":null,"product":"spindle assembly abnormal protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1223300","name":null,"product":"spindle assembly abnormal protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SAS4","evaluation":null}