{"gene":"CFAP91","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2020,"finding":"CFAP91 (encoded by MAATS1) is a calmodulin-associated and spoke-associated complex (CSC) protein essential for normal sperm flagellum structure; biallelic loss-of-function variants in MAATS1 cause severe central pair complex (CPC) and radial spoke defects in human sperm. WDR66 was identified as a physical and functional partner of CFAP91 within the CSC by co-immunoprecipitation and immunostaining.","method":"Exome sequencing, transmission electron microscopy, immunostaining, co-immunoprecipitation, RNAi knockdown of TbCFAP91 in Trypanosoma","journal":"Journal of medical genetics","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (TEM, immunostaining, Co-IP, RNAi in model organism) with functional phenotype replicated across human patients and Trypanosoma model","pmids":["32161152"],"is_preprint":false},{"year":2022,"finding":"Tetrahymena Cfap91 localizes to the base of radial spokes RS2 and RS3 and is required for stable docking/positioning of RS3 and the base of RS2, as well as adjacent inner dynein arms. Loss of Cfap91 reduces levels of RS3-specific proteins (Cfap61, Cfap251) and RS2-associated Cfap206, and Cfap91 interacts with the molecular ruler protein Ccdc39. CFAP91-KO cilia beat in an uncoordinated manner with dramatically reduced frequency, causing severely impaired swimming.","method":"Genetic knockout in Tetrahymena, proteomics, immunofluorescence microscopy, co-immunoprecipitation with Ccdc39","journal":"Cells","confidence":"High","confidence_rationale":"Tier 2 — genetic KO with defined ultrastructural and motility phenotype, proteomic and interaction data, consistent with human CFAP91 function","pmids":["36552811"],"is_preprint":false},{"year":2025,"finding":"CFAP91 is an essential scaffolder of radial spoke RS3 assembly in mammalian sperm flagella. Cfap91 KO mice exhibit impaired sperm flagellum formation and male infertility. CFAP91 immunoprecipitates with RS3 proteins CFAP251 and LRRC23, whose localization is disrupted in Cfap91 KO sperm. BioID2 proximity labeling identified EFCAB5 as a sperm-specific CFAP91-proximal component; Efcab5 KO males show reduced sperm motility and fertility.","method":"Cfap91 knockout mouse, FLAG/BioID2 proximity labeling, immunoprecipitation, immunofluorescence localization, Efcab5 knockout","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 — KO mouse with defined infertility phenotype, proximity labeling + Co-IP identifying specific RS3 partners, functional validation of downstream interactor EFCAB5","pmids":["40931011"],"is_preprint":false},{"year":2002,"finding":"AAT-1 (CFAP91) was identified as a testis-specific AMY-1-binding protein that forms a quaternary complex with AMY-1, S-AKAP84/AKAP149, and the regulatory subunit (RII) of cAMP-dependent protein kinase (PKA) in rat testis and HeLa cells. AAT-1alpha localizes to mitochondria, weakly stimulates PKA phosphorylation activity, and is itself phosphorylated by PKA both in vivo and in vitro.","method":"Yeast two-hybrid screening, co-immunoprecipitation, colocalization by immunofluorescence, in vitro and in vivo PKA phosphorylation assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP and in vitro kinase assay from single lab; quaternary complex formation supported by multiple methods","pmids":["12223483"],"is_preprint":false},{"year":2005,"finding":"Multiple AAT-1 (CFAP91) isoforms (AAT-1L, AAT-1M, AAT-1S, plus alpha/beta/gamma) were characterized; all isoforms bind AMY-1. AAT-1alpha and AAT-1S localize to a mitochondria-like structure, while AAT-1L and AAT-1M are diffusely cytoplasmic, indicating isoform-specific subcellular targeting.","method":"Isoform cloning, co-immunoprecipitation, immunofluorescence colocalization in human cells","journal":"Biological & pharmaceutical bulletin","confidence":"Medium","confidence_rationale":"Tier 3 — subcellular localization by imaging and binding confirmed by Co-IP, single lab","pmids":["15863901"],"is_preprint":false}],"current_model":"CFAP91 is an axonemal scaffolding protein that localizes to the base of radial spokes RS2 and RS3 in motile cilia and sperm flagella, where it is required for stable docking of RS3 (interacting with CFAP251, LRRC23, and EFCAB5) and for the assembly of adjacent inner dynein arms; loss of CFAP91 disrupts central pair complex and radial spoke integrity, causes uncoordinated ciliary beating, impairs sperm flagellum formation, and results in male infertility, while in somatic cells the testis-specific isoform AAT-1alpha also participates in a mitochondria-associated quaternary complex with AMY-1, S-AKAP84/AKAP149, and PKA-RII and is phosphorylated by PKA."},"narrative":{"teleology":[{"year":2002,"claim":"The initial identification of AAT-1 (CFAP91) as a testis-specific AMY-1-binding protein established that it participates in a mitochondria-associated quaternary complex with AMY-1, S-AKAP84/AKAP149, and PKA-RII, linking the protein to cAMP/PKA signaling in germ cells.","evidence":"Yeast two-hybrid, reciprocal co-immunoprecipitation, immunofluorescence colocalization, and in vitro/in vivo PKA phosphorylation assays in rat testis and HeLa cells","pmids":["12223483"],"confidence":"Medium","gaps":["Quaternary complex characterized by a single laboratory; independent validation in other systems lacking","Physiological significance of PKA phosphorylation of AAT-1 for sperm function not determined","Relationship of mitochondrial complex to axonemal role was unknown"]},{"year":2005,"claim":"Characterization of multiple AAT-1 isoforms revealed isoform-specific subcellular targeting, with AAT-1α localizing to mitochondria and longer isoforms distributing diffusely in the cytoplasm, suggesting functional diversification.","evidence":"Isoform cloning, co-immunoprecipitation, and immunofluorescence in human cells","pmids":["15863901"],"confidence":"Medium","gaps":["Single-lab study; isoform-specific functions not tested by loss-of-function approaches","Which isoforms are relevant for axonemal versus mitochondrial roles was unresolved"]},{"year":2020,"claim":"The discovery that biallelic MAATS1 (CFAP91) variants cause central pair complex and radial spoke defects in human sperm — and that CFAP91 physically interacts with WDR66 in the calmodulin-associated/spoke-associated complex — established CFAP91 as an essential structural component of the sperm axoneme and linked it to human male infertility.","evidence":"Exome sequencing of infertile men, transmission electron microscopy, immunostaining, co-immunoprecipitation, and RNAi knockdown in Trypanosoma brucei","pmids":["32161152"],"confidence":"High","gaps":["Precise position of CFAP91 within the axonemal repeat and its relationship to specific radial spokes not yet mapped","Mechanism by which loss of CFAP91 disrupts the central pair complex was unclear"]},{"year":2022,"claim":"Genetic knockout in Tetrahymena pinpointed CFAP91 to the base of radial spokes RS2 and RS3, demonstrating that it is required for RS3 docking and adjacent inner dynein arm assembly, and that it interacts with the molecular ruler protein CCDC39 — thereby resolving its structural position within the 96-nm axonemal repeat.","evidence":"CFAP91-KO Tetrahymena, quantitative proteomics of axonemes, co-immunoprecipitation with CCDC39, motility analysis","pmids":["36552811"],"confidence":"High","gaps":["Whether mammalian CFAP91 occupies the same position was not directly shown","Direct structural data (cryo-ET) of CFAP91 within the repeat unit was lacking"]},{"year":2025,"claim":"Cfap91 knockout mice confirmed the protein as an essential RS3 scaffold in mammalian sperm, identified CFAP251, LRRC23, and the sperm-specific EFCAB5 as direct or proximal interaction partners, and validated EFCAB5 as functionally important for sperm motility and fertility.","evidence":"Cfap91 and Efcab5 knockout mice, FLAG immunoprecipitation, BioID2 proximity labeling, immunofluorescence","pmids":["40931011"],"confidence":"High","gaps":["High-resolution structural model of the CFAP91-RS3 scaffold complex is not yet available","Whether CFAP91 has additional roles in somatic motile cilia beyond the ciliate model remains untested in mammals","Functional connection between the mitochondrial PKA-associated complex and the axonemal scaffolding role is unexplored"]},{"year":null,"claim":"A structural understanding of how CFAP91 bridges the molecular ruler (CCDC39/CCDC40) to RS3 and inner dynein arms, and whether the mitochondrial PKA-associated role of CFAP91 is functionally independent from its axonemal scaffolding function, remain open questions.","evidence":"","pmids":[],"confidence":"High","gaps":["No cryo-EM or cryo-ET structure of CFAP91 in the axonemal repeat","Relationship between mitochondrial/PKA signaling function and flagellar assembly function unresolved","Role of CFAP91 in primary ciliary dyskinesia or respiratory cilia not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[3,4]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1,2]}],"complexes":["Calmodulin-associated and spoke-associated complex (CSC)","AMY-1/S-AKAP84/PKA-RII quaternary complex"],"partners":["WDR66","CFAP251","LRRC23","EFCAB5","CCDC39","AMY1","AKAP1"],"other_free_text":[]},"mechanistic_narrative":"CFAP91 is an axonemal scaffolding protein that localizes to the base of radial spokes RS2 and RS3 in motile cilia and sperm flagella, where it is required for stable docking of RS3, proper assembly of adjacent inner dynein arms, and coordinated ciliary beating [PMID:36552811, PMID:40931011]. In sperm, CFAP91 physically interacts with RS3 components CFAP251, LRRC23, and the sperm-specific proximal protein EFCAB5; loss of CFAP91 disrupts RS3 protein localization and causes severe flagellar structural defects leading to male infertility in both mice and humans carrying biallelic loss-of-function variants [PMID:32161152, PMID:40931011]. A testis-enriched isoform (AAT-1α) additionally participates in a mitochondria-associated quaternary complex with AMY-1, S-AKAP84/AKAP149, and PKA-RII, and is phosphorylated by PKA, linking CFAP91 to cAMP-dependent signaling in the testis [PMID:12223483]."},"prefetch_data":{"uniprot":{"accession":"Q7Z4T9","full_name":"Cilia- and flagella-associated protein 91","aliases":["AMY-1-associating protein expressed in testis 1","AAT-1","MYCBP/AMY-1-associated testis-expressed protein 1","Protein MAATS1"],"length_aa":767,"mass_kda":90.0,"function":"Involved in sperm flagellum axonemal organization and function (PubMed:12223483, PubMed:32161152). May regulate cilium motility through its role in the assembly of the axonemal radial spokes (By similarity)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q7Z4T9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CFAP91","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CFAP91","total_profiled":1310},"omim":[{"mim_id":"619177","title":"SPERMATOGENIC FAILURE 51; SPGF51","url":"https://www.omim.org/entry/619177"},{"mim_id":"609910","title":"CILIA- AND FLAGELLA-ASSOCIATED PROTEIN 91; CFAP91","url":"https://www.omim.org/entry/609910"},{"mim_id":"258150","title":"SPERMATOGENIC FAILURE 1; SPGF1","url":"https://www.omim.org/entry/258150"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"choroid plexus","ntpm":15.4},{"tissue":"fallopian tube","ntpm":13.3}],"url":"https://www.proteinatlas.org/search/CFAP91"},"hgnc":{"alias_symbol":["AAT1","AAT1alpha","SPATA26","CaM-IP2","AAT-1"],"prev_symbol":["C3orf15","MAATS1"]},"alphafold":{"accession":"Q7Z4T9","domains":[{"cath_id":"-","chopping":"39-122","consensus_level":"high","plddt":77.6893,"start":39,"end":122},{"cath_id":"-","chopping":"235-355","consensus_level":"medium","plddt":91.0324,"start":235,"end":355},{"cath_id":"-","chopping":"358-414","consensus_level":"medium","plddt":82.7554,"start":358,"end":414},{"cath_id":"1.20.5","chopping":"493-531","consensus_level":"medium","plddt":82.4218,"start":493,"end":531},{"cath_id":"1.20.5","chopping":"548-685","consensus_level":"high","plddt":89.1578,"start":548,"end":685},{"cath_id":"1.20.5","chopping":"698-751","consensus_level":"high","plddt":74.0506,"start":698,"end":751}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z4T9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z4T9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z4T9-F1-predicted_aligned_error_v6.png","plddt_mean":74.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CFAP91","jax_strain_url":"https://www.jax.org/strain/search?query=CFAP91"},"sequence":{"accession":"Q7Z4T9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z4T9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z4T9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z4T9"}},"corpus_meta":[{"pmid":"37169919","id":"PMC_37169919","title":"Chloroquine 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WDR66 was identified as a physical and functional partner of CFAP91 within the CSC by co-immunoprecipitation and immunostaining.\",\n      \"method\": \"Exome sequencing, transmission electron microscopy, immunostaining, co-immunoprecipitation, RNAi knockdown of TbCFAP91 in Trypanosoma\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (TEM, immunostaining, Co-IP, RNAi in model organism) with functional phenotype replicated across human patients and Trypanosoma model\",\n      \"pmids\": [\"32161152\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Tetrahymena Cfap91 localizes to the base of radial spokes RS2 and RS3 and is required for stable docking/positioning of RS3 and the base of RS2, as well as adjacent inner dynein arms. Loss of Cfap91 reduces levels of RS3-specific proteins (Cfap61, Cfap251) and RS2-associated Cfap206, and Cfap91 interacts with the molecular ruler protein Ccdc39. CFAP91-KO cilia beat in an uncoordinated manner with dramatically reduced frequency, causing severely impaired swimming.\",\n      \"method\": \"Genetic knockout in Tetrahymena, proteomics, immunofluorescence microscopy, co-immunoprecipitation with Ccdc39\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with defined ultrastructural and motility phenotype, proteomic and interaction data, consistent with human CFAP91 function\",\n      \"pmids\": [\"36552811\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CFAP91 is an essential scaffolder of radial spoke RS3 assembly in mammalian sperm flagella. Cfap91 KO mice exhibit impaired sperm flagellum formation and male infertility. CFAP91 immunoprecipitates with RS3 proteins CFAP251 and LRRC23, whose localization is disrupted in Cfap91 KO sperm. BioID2 proximity labeling identified EFCAB5 as a sperm-specific CFAP91-proximal component; Efcab5 KO males show reduced sperm motility and fertility.\",\n      \"method\": \"Cfap91 knockout mouse, FLAG/BioID2 proximity labeling, immunoprecipitation, immunofluorescence localization, Efcab5 knockout\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — KO mouse with defined infertility phenotype, proximity labeling + Co-IP identifying specific RS3 partners, functional validation of downstream interactor EFCAB5\",\n      \"pmids\": [\"40931011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"AAT-1 (CFAP91) was identified as a testis-specific AMY-1-binding protein that forms a quaternary complex with AMY-1, S-AKAP84/AKAP149, and the regulatory subunit (RII) of cAMP-dependent protein kinase (PKA) in rat testis and HeLa cells. AAT-1alpha localizes to mitochondria, weakly stimulates PKA phosphorylation activity, and is itself phosphorylated by PKA both in vivo and in vitro.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, colocalization by immunofluorescence, in vitro and in vivo PKA phosphorylation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and in vitro kinase assay from single lab; quaternary complex formation supported by multiple methods\",\n      \"pmids\": [\"12223483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Multiple AAT-1 (CFAP91) isoforms (AAT-1L, AAT-1M, AAT-1S, plus alpha/beta/gamma) were characterized; all isoforms bind AMY-1. AAT-1alpha and AAT-1S localize to a mitochondria-like structure, while AAT-1L and AAT-1M are diffusely cytoplasmic, indicating isoform-specific subcellular targeting.\",\n      \"method\": \"Isoform cloning, co-immunoprecipitation, immunofluorescence colocalization in human cells\",\n      \"journal\": \"Biological & pharmaceutical bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — subcellular localization by imaging and binding confirmed by Co-IP, single lab\",\n      \"pmids\": [\"15863901\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CFAP91 is an axonemal scaffolding protein that localizes to the base of radial spokes RS2 and RS3 in motile cilia and sperm flagella, where it is required for stable docking of RS3 (interacting with CFAP251, LRRC23, and EFCAB5) and for the assembly of adjacent inner dynein arms; loss of CFAP91 disrupts central pair complex and radial spoke integrity, causes uncoordinated ciliary beating, impairs sperm flagellum formation, and results in male infertility, while in somatic cells the testis-specific isoform AAT-1alpha also participates in a mitochondria-associated quaternary complex with AMY-1, S-AKAP84/AKAP149, and PKA-RII and is phosphorylated by PKA.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CFAP91 is an axonemal scaffolding protein that localizes to the base of radial spokes RS2 and RS3 in motile cilia and sperm flagella, where it is required for stable docking of RS3, proper assembly of adjacent inner dynein arms, and coordinated ciliary beating [PMID:36552811, PMID:40931011]. In sperm, CFAP91 physically interacts with RS3 components CFAP251, LRRC23, and the sperm-specific proximal protein EFCAB5; loss of CFAP91 disrupts RS3 protein localization and causes severe flagellar structural defects leading to male infertility in both mice and humans carrying biallelic loss-of-function variants [PMID:32161152, PMID:40931011]. A testis-enriched isoform (AAT-1α) additionally participates in a mitochondria-associated quaternary complex with AMY-1, S-AKAP84/AKAP149, and PKA-RII, and is phosphorylated by PKA, linking CFAP91 to cAMP-dependent signaling in the testis [PMID:12223483].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"The initial identification of AAT-1 (CFAP91) as a testis-specific AMY-1-binding protein established that it participates in a mitochondria-associated quaternary complex with AMY-1, S-AKAP84/AKAP149, and PKA-RII, linking the protein to cAMP/PKA signaling in germ cells.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal co-immunoprecipitation, immunofluorescence colocalization, and in vitro/in vivo PKA phosphorylation assays in rat testis and HeLa cells\",\n      \"pmids\": [\"12223483\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Quaternary complex characterized by a single laboratory; independent validation in other systems lacking\",\n        \"Physiological significance of PKA phosphorylation of AAT-1 for sperm function not determined\",\n        \"Relationship of mitochondrial complex to axonemal role was unknown\"\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Characterization of multiple AAT-1 isoforms revealed isoform-specific subcellular targeting, with AAT-1α localizing to mitochondria and longer isoforms distributing diffusely in the cytoplasm, suggesting functional diversification.\",\n      \"evidence\": \"Isoform cloning, co-immunoprecipitation, and immunofluorescence in human cells\",\n      \"pmids\": [\"15863901\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; isoform-specific functions not tested by loss-of-function approaches\",\n        \"Which isoforms are relevant for axonemal versus mitochondrial roles was unresolved\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The discovery that biallelic MAATS1 (CFAP91) variants cause central pair complex and radial spoke defects in human sperm — and that CFAP91 physically interacts with WDR66 in the calmodulin-associated/spoke-associated complex — established CFAP91 as an essential structural component of the sperm axoneme and linked it to human male infertility.\",\n      \"evidence\": \"Exome sequencing of infertile men, transmission electron microscopy, immunostaining, co-immunoprecipitation, and RNAi knockdown in Trypanosoma brucei\",\n      \"pmids\": [\"32161152\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise position of CFAP91 within the axonemal repeat and its relationship to specific radial spokes not yet mapped\",\n        \"Mechanism by which loss of CFAP91 disrupts the central pair complex was unclear\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Genetic knockout in Tetrahymena pinpointed CFAP91 to the base of radial spokes RS2 and RS3, demonstrating that it is required for RS3 docking and adjacent inner dynein arm assembly, and that it interacts with the molecular ruler protein CCDC39 — thereby resolving its structural position within the 96-nm axonemal repeat.\",\n      \"evidence\": \"CFAP91-KO Tetrahymena, quantitative proteomics of axonemes, co-immunoprecipitation with CCDC39, motility analysis\",\n      \"pmids\": [\"36552811\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether mammalian CFAP91 occupies the same position was not directly shown\",\n        \"Direct structural data (cryo-ET) of CFAP91 within the repeat unit was lacking\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Cfap91 knockout mice confirmed the protein as an essential RS3 scaffold in mammalian sperm, identified CFAP251, LRRC23, and the sperm-specific EFCAB5 as direct or proximal interaction partners, and validated EFCAB5 as functionally important for sperm motility and fertility.\",\n      \"evidence\": \"Cfap91 and Efcab5 knockout mice, FLAG immunoprecipitation, BioID2 proximity labeling, immunofluorescence\",\n      \"pmids\": [\"40931011\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"High-resolution structural model of the CFAP91-RS3 scaffold complex is not yet available\",\n        \"Whether CFAP91 has additional roles in somatic motile cilia beyond the ciliate model remains untested in mammals\",\n        \"Functional connection between the mitochondrial PKA-associated complex and the axonemal scaffolding role is unexplored\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A structural understanding of how CFAP91 bridges the molecular ruler (CCDC39/CCDC40) to RS3 and inner dynein arms, and whether the mitochondrial PKA-associated role of CFAP91 is functionally independent from its axonemal scaffolding function, remain open questions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No cryo-EM or cryo-ET structure of CFAP91 in the axonemal repeat\",\n        \"Relationship between mitochondrial/PKA signaling function and flagellar assembly function unresolved\",\n        \"Role of CFAP91 in primary ciliary dyskinesia or respiratory cilia not established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\n      \"Calmodulin-associated and spoke-associated complex (CSC)\",\n      \"AMY-1/S-AKAP84/PKA-RII quaternary complex\"\n    ],\n    \"partners\": [\n      \"WDR66\",\n      \"CFAP251\",\n      \"LRRC23\",\n      \"EFCAB5\",\n      \"CCDC39\",\n      \"AMY1\",\n      \"AKAP1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}