{"gene":"PF3D7_0607600","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2014,"finding":"In P. berghei, genetic knockout of SAS6 (sas6) results in severely abnormal male gametogenesis: reduced basal body numbers, axonemal assembly defects, and abnormal nuclear allocation, establishing that SAS6 is required for basal body assembly and duplication during male gamete development. Additionally, loss of SAS6 blocks transmission from mosquito to vertebrate host, revealing a role in the ookinete-to-sporulating oocyst transition.","method":"Genetic knockout (loss-of-function) with electron microscopy and transmission assays","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with multiple specific phenotypic readouts (basal body number, axoneme assembly, nuclear allocation, fertilization rate, mosquito infectivity) in P. berghei","pmids":["25154861"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"In P. berghei, the eight basal bodies are concomitantly de novo assembled in a SAS6- and SAS4-dependent manner from a deuterosome-like structure. Within the basal body, centrin and SAS6 form distinct subdomains surrounded by a SAS4-toroid in the lumen of the microtubule wall (proximal and central cores are fused). This was established by ultrastructure expansion microscopy (U-ExM) combined with Pan-ExM and bulk proteome labelling.","method":"Ultrastructure expansion microscopy (U-ExM), Pan-ExM, bulk proteome labelling, 3D reconstruction","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — direct structural localisation by U-ExM/Pan-ExM with 3D reconstruction in a single lab; SAS6-dependent assembly also supported by prior knockout data (PMID 25154861)","pmids":["35077503"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"Plasmodium SAS6 (PF3D7_0607600) is a basal body component required for de novo concomitant assembly of basal bodies from a deuterosome-like structure during male gametogenesis; within the basal body it occupies the proximal/central core lumen alongside centrin and surrounded by a SAS4-toroid, and its loss causes reduced basal body numbers, axonemal assembly defects, abnormal nuclear allocation, and blocks mosquito-to-vertebrate transmission."},"narrative":{"mechanistic_narrative":"SAS6 (PF3D7_0607600) is a basal body component required for the de novo assembly and duplication of basal bodies during male gametogenesis in Plasmodium [PMID:25154861, PMID:35077503]. In P. berghei, genetic knockout of SAS6 severely disrupts male gametogenesis, producing reduced basal body numbers, axonemal assembly defects, and abnormal nuclear allocation, and it blocks transmission from mosquito to vertebrate host at the ookinete-to-sporulating oocyst transition [PMID:25154861]. Structurally, the eight basal bodies are concomitantly assembled de novo from a deuterosome-like structure in a manner dependent on both SAS6 and SAS4; within each basal body, SAS6 and centrin occupy distinct subdomains of the fused proximal/central core lumen, surrounded by a SAS4-toroid inside the microtubule wall [PMID:35077503]. Beyond this basal body assembly role established in P. berghei, no further mechanistic detail for SAS6 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"It was unknown what drives basal body formation and male gamete maturation in Plasmodium; knocking out SAS6 established that it is required for basal body assembly and duplication and for onward transmission to the mosquito vector.","evidence":"Genetic knockout with electron microscopy and transmission assays in P. berghei","pmids":["25154861"],"confidence":"High","gaps":["Does not resolve the molecular activity of SAS6 (e.g. self-oligomerization or partner binding) underlying basal body assembly","Mechanism linking basal body loss to abnormal nuclear allocation not defined","No P. falciparum data despite the subject gene identifier being PF3D7_0607600"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"The spatial architecture and assembly route of the basal body were unknown; expansion microscopy placed SAS6 in a distinct core subdomain and showed the eight basal bodies arise concomitantly de novo from a deuterosome-like structure in a SAS6/SAS4-dependent manner.","evidence":"Ultrastructure expansion microscopy (U-ExM), Pan-ExM, bulk proteome labelling, and 3D reconstruction in P. berghei","pmids":["35077503"],"confidence":"High","gaps":["The direct molecular interaction between SAS6, SAS4, and centrin within the core is not biochemically defined","How SAS6 is recruited to or nucleates the deuterosome-like structure is unresolved","Single-lab structural characterization"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The biochemical activity of SAS6 and its direct binding partners within the basal body core remain undefined, as does whether its role is conserved in P. falciparum.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstitution or direct interaction assay establishing SAS6 molecular activity","No characterization in P. falciparum (PF3D7_0607600) itself","Structural relationship of SAS6 to centrin and SAS4 shown by localization but not by direct binding data"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["basal body core (SAS6 and centrin subdomains surrounded by SAS4-toroid)"],"partners":["SAS4 (CO-DEPENDENT FOR DE NOVO BASAL BODY ASSEMBLY)","CENTRIN (ADJACENT CORE SUBDOMAIN)"],"other_free_text":["Eight basal bodies assembled concomitantly de novo from a deuterosome-like structure in a SAS6/SAS4-dependent manner (P. berghei) [#1]","Loss of SAS6 blocks mosquito-to-vertebrate transmission at the ookinete-to-sporulating oocyst transition (P. berghei) [#0]","All experimental evidence derives from the P. berghei ortholog; no direct P. falciparum data in the corpus"]}},"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":["SAS6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25154861","id":"PMC_25154861","title":"An essential role of the basal body protein SAS-6 in Plasmodium male gamete development and malaria transmission.","date":"2014","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25154861","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAS6","PbSAS6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27339728","id":"PMC_27339728","title":"SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27339728","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SAS6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4355,"output_tokens":727,"usd":0.011985,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5411,"output_tokens":1681,"usd":0.03454,"stage2_stop_reason":"end_turn"},"total_usd":0.046525,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"In P. berghei, genetic knockout of SAS6 (sas6) results in severely abnormal male gametogenesis: reduced basal body numbers, axonemal assembly defects, and abnormal nuclear allocation, establishing that SAS6 is required for basal body assembly and duplication during male gamete development. Additionally, loss of SAS6 blocks transmission from mosquito to vertebrate host, revealing a role in the ookinete-to-sporulating oocyst transition.\",\n      \"method\": \"Genetic knockout (loss-of-function) with electron microscopy and transmission assays\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with multiple specific phenotypic readouts (basal body number, axoneme assembly, nuclear allocation, fertilization rate, mosquito infectivity) in P. berghei\",\n      \"pmids\": [\"25154861\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. berghei, the eight basal bodies are concomitantly de novo assembled in a SAS6- and SAS4-dependent manner from a deuterosome-like structure. Within the basal body, centrin and SAS6 form distinct subdomains surrounded by a SAS4-toroid in the lumen of the microtubule wall (proximal and central cores are fused). This was established by ultrastructure expansion microscopy (U-ExM) combined with Pan-ExM and bulk proteome labelling.\",\n      \"method\": \"Ultrastructure expansion microscopy (U-ExM), Pan-ExM, bulk proteome labelling, 3D reconstruction\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct structural localisation by U-ExM/Pan-ExM with 3D reconstruction in a single lab; SAS6-dependent assembly also supported by prior knockout data (PMID 25154861)\",\n      \"pmids\": [\"35077503\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"Plasmodium SAS6 (PF3D7_0607600) is a basal body component required for de novo concomitant assembly of basal bodies from a deuterosome-like structure during male gametogenesis; within the basal body it occupies the proximal/central core lumen alongside centrin and surrounded by a SAS4-toroid, and its loss causes reduced basal body numbers, axonemal assembly defects, abnormal nuclear allocation, and blocks mosquito-to-vertebrate transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SAS6 (PF3D7_0607600) is a basal body component required for the de novo assembly and duplication of basal bodies during male gametogenesis in Plasmodium [#0, #1]. In P. berghei, genetic knockout of SAS6 severely disrupts male gametogenesis, producing reduced basal body numbers, axonemal assembly defects, and abnormal nuclear allocation, and it blocks transmission from mosquito to vertebrate host at the ookinete-to-sporulating oocyst transition [#0]. Structurally, the eight basal bodies are concomitantly assembled de novo from a deuterosome-like structure in a manner dependent on both SAS6 and SAS4; within each basal body, SAS6 and centrin occupy distinct subdomains of the fused proximal/central core lumen, surrounded by a SAS4-toroid inside the microtubule wall [#1]. Beyond this basal body assembly role established in P. berghei, no further mechanistic detail for SAS6 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"It was unknown what drives basal body formation and male gamete maturation in Plasmodium; knocking out SAS6 established that it is required for basal body assembly and duplication and for onward transmission to the mosquito vector.\",\n      \"evidence\": \"Genetic knockout with electron microscopy and transmission assays in P. berghei\",\n      \"pmids\": [\"25154861\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not resolve the molecular activity of SAS6 (e.g. self-oligomerization or partner binding) underlying basal body assembly\",\n        \"Mechanism linking basal body loss to abnormal nuclear allocation not defined\",\n        \"No P. falciparum data despite the subject gene identifier being PF3D7_0607600\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The spatial architecture and assembly route of the basal body were unknown; expansion microscopy placed SAS6 in a distinct core subdomain and showed the eight basal bodies arise concomitantly de novo from a deuterosome-like structure in a SAS6/SAS4-dependent manner.\",\n      \"evidence\": \"Ultrastructure expansion microscopy (U-ExM), Pan-ExM, bulk proteome labelling, and 3D reconstruction in P. berghei\",\n      \"pmids\": [\"35077503\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The direct molecular interaction between SAS6, SAS4, and centrin within the core is not biochemically defined\",\n        \"How SAS6 is recruited to or nucleates the deuterosome-like structure is unresolved\",\n        \"Single-lab structural characterization\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of SAS6 and its direct binding partners within the basal body core remain undefined, as does whether its role is conserved in P. falciparum.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution or direct interaction assay establishing SAS6 molecular activity\",\n        \"No characterization in P. falciparum (PF3D7_0607600) itself\",\n        \"Structural relationship of SAS6 to centrin and SAS4 shown by localization but not by direct binding data\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"basal body\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"male gametogenesis\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"basal body assembly\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"basal body core (SAS6 and centrin subdomains surrounded by SAS4-toroid)\"\n    ],\n    \"partners\": [\n      \"SAS4 (co-dependent for de novo basal body assembly)\",\n      \"centrin (adjacent core subdomain)\"\n    ],\n    \"other_free_text\": [\n      \"Eight basal bodies assembled concomitantly de novo from a deuterosome-like structure in a SAS6/SAS4-dependent manner (P. berghei) [#1]\",\n      \"Loss of SAS6 blocks mosquito-to-vertebrate transmission at the ookinete-to-sporulating oocyst transition (P. berghei) [#0]\",\n      \"All experimental evidence derives from the P. berghei ortholog; no direct P. falciparum data in the corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0607600","name":null,"product":"spindle assembly abnormal protein 6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0106200","name":null,"product":"spindle assembly abnormal protein 6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1142700","name":null,"product":"spindle assembly abnormal protein 6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SAS6","evaluation":null}