{"gene":"CFAP91","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2002,"finding":"AAT-1 (CFAP91 alias) was identified as a novel AMY-1-binding protein expressed specifically in the testis during spermatogenesis. AAT-1alpha 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, where AAT-1alpha is associated with RII via S-AKAP84/AKAP149. AAT-1alpha weakly stimulates PKA phosphorylation activity and is itself phosphorylated by PKA both in vivo and in vitro. AAT-1alpha co-localizes with AMY-1 in mitochondria.","method":"Yeast two-hybrid screening, co-immunoprecipitation, subcellular colocalization, in vivo and in vitro kinase assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, in vitro kinase assay, localization; single lab with multiple orthogonal methods","pmids":["12223483"],"is_preprint":false},{"year":2005,"finding":"Additional splicing isoforms of AAT-1 (AAT-1L, AAT-1M, AAT-1S) were identified, using a different promoter than AAT-1alpha/-beta/-gamma. All isoforms bind AMY-1 and co-localize with it in human cells. AAT-1L and AAT-1M are localized diffusely in the cytoplasm, while AAT-1S (like AAT-1alpha) localizes to a mitochondria-like structure, indicating isoform-specific subcellular localization.","method":"Molecular cloning, immunofluorescence/colocalization, co-immunoprecipitation","journal":"Biological & pharmaceutical bulletin","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single colocalization/pulldown method per isoform, no functional rescue","pmids":["15863901"],"is_preprint":false},{"year":2020,"finding":"Biallelic loss-of-function variants in MAATS1 (encoding CFAP91) cause severe asthenoteratozoospermia in men. Immunostaining and TEM of patient sperm showed severe central pair complex (CPC) and radial spoke defects. WDR66 was confirmed as a physical and functional partner of CFAP91 in the calmodulin-associated and spoke-associated complex (CSC). RNAi knockdown of the Trypanosoma ortholog (TbCFAP91) impaired flagellar movement and caused CPC defects, confirming conserved axonemal localization and function.","method":"Exome sequencing, immunostaining, transmission electron microscopy, co-immunoprecipitation (WDR66 interaction), RNAi knockdown in Trypanosoma","journal":"Journal of medical genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (TEM, immunostaining, Co-IP, RNAi functional rescue in model organism), replicated across human patients and Trypanosoma model","pmids":["32161152"],"is_preprint":false},{"year":2022,"finding":"In Tetrahymena, Cfap91 is required for the stable docking/positioning of radial spoke RS3 and the base of RS2, and adjacent inner dynein arms. CFAP91-KO cells showed significantly diminished levels of RS3-specific proteins (Cfap61, Cfap251) and RS2-associated Cfap206. Cfap91 interacts with the molecular ruler protein Ccdc39. CFAP91-KO cilia beat in an uncoordinated manner with dramatically reduced beating frequency, causing cells to swim ~100 times slower than wild-type.","method":"Genetic knockout, proteomics/mass spectrometry, immunofluorescence microscopy, swimming speed measurements","journal":"Cells","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined ciliary phenotype, proteomic identification of interaction partners, multiple orthogonal methods in single study","pmids":["36552811"],"is_preprint":false},{"year":2025,"finding":"CFAP91 is an essential scaffolder of radial spoke RS3 assembly in mammalian spermatozoa. 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. Proximity labeling (BioID2) in mature spermatozoa identified EFCAB5 as a sperm-specific CFAP91-proximal component; Efcab5 KO males show reduced sperm motility and fertility.","method":"Knockout mouse model, FLAG-BioID2 proximity labeling, co-immunoprecipitation, immunofluorescence localization","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vivo KO with defined fertility/motility phenotype, proximity labeling plus Co-IP for partner identification, multiple orthogonal methods in single study","pmids":["40931011"],"is_preprint":false}],"current_model":"CFAP91 (also known as MAATS1/AAT-1) is an axonemal scaffolding protein of the calmodulin- and spoke-associated complex (CSC) that localizes to the base of radial spokes RS2 and RS3 in cilia and sperm flagella, where it is required for the stable docking of RS3 (and the RS2 base), adjacent inner dynein arms, and associated proteins (CFAP251, LRRC23, CFAP206); it physically interacts with WDR66, CFAP251, LRRC23, and the ruler protein CCDC39, and its loss causes severe axonemal structural defects, uncoordinated ciliary beating, and male infertility; in somatic cells, the testis-specific AAT-1alpha isoform additionally forms a mitochondria-localized quaternary complex with AMY-1, S-AKAP84/AKAP149, and the PKA regulatory subunit RII, and is phosphorylated by PKA."},"narrative":{"mechanistic_narrative":"CFAP91 (MAATS1/AAT-1) is an axonemal scaffolding protein that organizes the radial spoke architecture of motile cilia and sperm flagella [PMID:32161152, PMID:36552811]. Within the calmodulin- and spoke-associated complex (CSC), it physically partners with WDR66 and is required for the stable docking and positioning of radial spoke RS3 and the base of RS2 together with adjacent inner dynein arms; its loss depletes RS3-associated proteins (CFAP251/CFAP61, LRRC23) and the RS2-associated CFAP206, and it engages the molecular ruler protein CCDC39 that templates axonemal spacing [PMID:32161152, PMID:36552811, PMID:40931011]. Loss of CFAP91 produces uncoordinated ciliary beating with dramatically reduced frequency in Tetrahymena and severe central-pair and radial-spoke defects, and in humans biallelic loss-of-function MAATS1 variants cause asthenoteratozoospermia while Cfap91-knockout mice show defective flagellum formation and male infertility [PMID:32161152, PMID:36552811, PMID:40931011]. Proximity labeling in mature spermatozoa identifies the sperm-specific component EFCAB5 near CFAP91, whose own loss reduces sperm motility [PMID:40931011]. Independently of its axonemal role, the testis-specific AAT-1alpha isoform localizes to mitochondria and assembles into a quaternary complex with AMY-1, S-AKAP84/AKAP149, and the PKA regulatory subunit RII, where it is phosphorylated by PKA and weakly stimulates PKA activity [PMID:12223483].","teleology":[{"year":2002,"claim":"Established the first molecular interactions of the protein by identifying AAT-1 as a testis-specific AMY-1 binding partner that scaffolds a PKA-anchoring complex at mitochondria.","evidence":"Yeast two-hybrid, reciprocal Co-IP, subcellular colocalization, and in vitro/in vivo kinase assays in rat testis and HeLa cells","pmids":["12223483"],"confidence":"Medium","gaps":["Does not connect the protein to ciliary/flagellar axoneme function","Functional consequence of PKA phosphorylation on the complex not defined","Relationship between the mitochondrial AAT-1alpha isoform and the axonemal pool unresolved"]},{"year":2005,"claim":"Defined isoform diversity, showing alternative promoters generate variants with distinct cytoplasmic versus mitochondrial localization while retaining AMY-1 binding.","evidence":"Molecular cloning, immunofluorescence colocalization, and Co-IP in human cells","pmids":["15863901"],"confidence":"Low","gaps":["Single colocalization/pulldown method per isoform with no functional rescue","Physiological role of each isoform not established","No link to axonemal assembly"]},{"year":2020,"claim":"Reframed the gene as an axonemal CSC component by linking loss-of-function to human asthenoteratozoospermia and demonstrating conserved flagellar function.","evidence":"Exome sequencing of infertile men, sperm immunostaining and TEM, Co-IP for WDR66, and RNAi knockdown in Trypanosoma","pmids":["32161152"],"confidence":"High","gaps":["Precise position within radial spoke architecture not yet mapped","Mechanism of WDR66 cooperation undefined","Full partner set not identified"]},{"year":2022,"claim":"Resolved the molecular role as a docking scaffold for RS3 and the RS2 base, defining the proteins whose assembly depends on it and the ruler protein it engages.","evidence":"Genetic knockout, proteomics, immunofluorescence, and swimming-speed assays in Tetrahymena","pmids":["36552811"],"confidence":"High","gaps":["Direct versus indirect nature of the CCDC39 interaction not dissected","Structural mechanism of spoke docking unknown","Whether mitochondrial and axonemal functions share a common domain unresolved"]},{"year":2025,"claim":"Confirmed the RS3-scaffolding role in mammalian sperm in vivo and identified a sperm-specific proximal partner essential for motility.","evidence":"Cfap91 knockout mice, FLAG-BioID2 proximity labeling, Co-IP, and immunofluorescence in spermatozoa","pmids":["40931011"],"confidence":"High","gaps":["Direct interaction versus proximity for EFCAB5 not distinguished","Structural model of the assembled RS3 scaffold lacking","How CFAP91 coordinates with the central pair complex not detailed"]},{"year":null,"claim":"How the testis-specific mitochondrial PKA-anchoring function relates mechanistically to the axonemal radial-spoke scaffolding role remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of CFAP91 within the radial spoke","Functional integration of mitochondrial AKAP complex and axonemal scaffolding undefined","Atomic-level basis of partner recruitment unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,3,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,3,4]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2,3]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,4]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[2,4]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[3,4]}],"complexes":["calmodulin- and spoke-associated complex (CSC)","radial spoke RS3","AMY-1/AKAP149/PKA-RII quaternary complex"],"partners":["WDR66","CFAP251","LRRC23","CCDC39","CFAP206","EFCAB5","AMY-1","AKAP149"],"other_free_text":[]}},"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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AAT-1alpha 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, where AAT-1alpha is associated with RII via S-AKAP84/AKAP149. AAT-1alpha weakly stimulates PKA phosphorylation activity and is itself phosphorylated by PKA both in vivo and in vitro. AAT-1alpha co-localizes with AMY-1 in mitochondria.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, subcellular colocalization, in vivo and in vitro kinase assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, in vitro kinase assay, localization; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"12223483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Additional splicing isoforms of AAT-1 (AAT-1L, AAT-1M, AAT-1S) were identified, using a different promoter than AAT-1alpha/-beta/-gamma. All isoforms bind AMY-1 and co-localize with it in human cells. AAT-1L and AAT-1M are localized diffusely in the cytoplasm, while AAT-1S (like AAT-1alpha) localizes to a mitochondria-like structure, indicating isoform-specific subcellular localization.\",\n      \"method\": \"Molecular cloning, immunofluorescence/colocalization, co-immunoprecipitation\",\n      \"journal\": \"Biological & pharmaceutical bulletin\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single colocalization/pulldown method per isoform, no functional rescue\",\n      \"pmids\": [\"15863901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Biallelic loss-of-function variants in MAATS1 (encoding CFAP91) cause severe asthenoteratozoospermia in men. Immunostaining and TEM of patient sperm showed severe central pair complex (CPC) and radial spoke defects. WDR66 was confirmed as a physical and functional partner of CFAP91 in the calmodulin-associated and spoke-associated complex (CSC). RNAi knockdown of the Trypanosoma ortholog (TbCFAP91) impaired flagellar movement and caused CPC defects, confirming conserved axonemal localization and function.\",\n      \"method\": \"Exome sequencing, immunostaining, transmission electron microscopy, co-immunoprecipitation (WDR66 interaction), RNAi knockdown in Trypanosoma\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (TEM, immunostaining, Co-IP, RNAi functional rescue in model organism), replicated across human patients and Trypanosoma model\",\n      \"pmids\": [\"32161152\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Tetrahymena, Cfap91 is required for the stable docking/positioning of radial spoke RS3 and the base of RS2, and adjacent inner dynein arms. CFAP91-KO cells showed significantly diminished levels of RS3-specific proteins (Cfap61, Cfap251) and RS2-associated Cfap206. Cfap91 interacts with the molecular ruler protein Ccdc39. CFAP91-KO cilia beat in an uncoordinated manner with dramatically reduced beating frequency, causing cells to swim ~100 times slower than wild-type.\",\n      \"method\": \"Genetic knockout, proteomics/mass spectrometry, immunofluorescence microscopy, swimming speed measurements\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined ciliary phenotype, proteomic identification of interaction partners, multiple orthogonal methods in single study\",\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 spermatozoa. 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. Proximity labeling (BioID2) in mature spermatozoa identified EFCAB5 as a sperm-specific CFAP91-proximal component; Efcab5 KO males show reduced sperm motility and fertility.\",\n      \"method\": \"Knockout mouse model, FLAG-BioID2 proximity labeling, co-immunoprecipitation, immunofluorescence localization\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vivo KO with defined fertility/motility phenotype, proximity labeling plus Co-IP for partner identification, multiple orthogonal methods in single study\",\n      \"pmids\": [\"40931011\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CFAP91 (also known as MAATS1/AAT-1) is an axonemal scaffolding protein of the calmodulin- and spoke-associated complex (CSC) that localizes to the base of radial spokes RS2 and RS3 in cilia and sperm flagella, where it is required for the stable docking of RS3 (and the RS2 base), adjacent inner dynein arms, and associated proteins (CFAP251, LRRC23, CFAP206); it physically interacts with WDR66, CFAP251, LRRC23, and the ruler protein CCDC39, and its loss causes severe axonemal structural defects, uncoordinated ciliary beating, and male infertility; in somatic cells, the testis-specific AAT-1alpha isoform additionally forms a mitochondria-localized quaternary complex with AMY-1, S-AKAP84/AKAP149, and the PKA regulatory subunit RII, and is phosphorylated by PKA.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CFAP91 (MAATS1/AAT-1) is an axonemal scaffolding protein that organizes the radial spoke architecture of motile cilia and sperm flagella [#2, #3]. Within the calmodulin- and spoke-associated complex (CSC), it physically partners with WDR66 and is required for the stable docking and positioning of radial spoke RS3 and the base of RS2 together with adjacent inner dynein arms; its loss depletes RS3-associated proteins (CFAP251/CFAP61, LRRC23) and the RS2-associated CFAP206, and it engages the molecular ruler protein CCDC39 that templates axonemal spacing [#2, #3, #4]. Loss of CFAP91 produces uncoordinated ciliary beating with dramatically reduced frequency in Tetrahymena and severe central-pair and radial-spoke defects, and in humans biallelic loss-of-function MAATS1 variants cause asthenoteratozoospermia while Cfap91-knockout mice show defective flagellum formation and male infertility [#2, #3, #4]. Proximity labeling in mature spermatozoa identifies the sperm-specific component EFCAB5 near CFAP91, whose own loss reduces sperm motility [#4]. Independently of its axonemal role, the testis-specific AAT-1alpha isoform localizes to mitochondria and assembles into a quaternary complex with AMY-1, S-AKAP84/AKAP149, and the PKA regulatory subunit RII, where it is phosphorylated by PKA and weakly stimulates PKA activity [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established the first molecular interactions of the protein by identifying AAT-1 as a testis-specific AMY-1 binding partner that scaffolds a PKA-anchoring complex at mitochondria.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP, subcellular colocalization, and in vitro/in vivo kinase assays in rat testis and HeLa cells\",\n      \"pmids\": [\"12223483\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not connect the protein to ciliary/flagellar axoneme function\", \"Functional consequence of PKA phosphorylation on the complex not defined\", \"Relationship between the mitochondrial AAT-1alpha isoform and the axonemal pool unresolved\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Defined isoform diversity, showing alternative promoters generate variants with distinct cytoplasmic versus mitochondrial localization while retaining AMY-1 binding.\",\n      \"evidence\": \"Molecular cloning, immunofluorescence colocalization, and Co-IP in human cells\",\n      \"pmids\": [\"15863901\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single colocalization/pulldown method per isoform with no functional rescue\", \"Physiological role of each isoform not established\", \"No link to axonemal assembly\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Reframed the gene as an axonemal CSC component by linking loss-of-function to human asthenoteratozoospermia and demonstrating conserved flagellar function.\",\n      \"evidence\": \"Exome sequencing of infertile men, sperm immunostaining and TEM, Co-IP for WDR66, and RNAi knockdown in Trypanosoma\",\n      \"pmids\": [\"32161152\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise position within radial spoke architecture not yet mapped\", \"Mechanism of WDR66 cooperation undefined\", \"Full partner set not identified\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Resolved the molecular role as a docking scaffold for RS3 and the RS2 base, defining the proteins whose assembly depends on it and the ruler protein it engages.\",\n      \"evidence\": \"Genetic knockout, proteomics, immunofluorescence, and swimming-speed assays in Tetrahymena\",\n      \"pmids\": [\"36552811\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct versus indirect nature of the CCDC39 interaction not dissected\", \"Structural mechanism of spoke docking unknown\", \"Whether mitochondrial and axonemal functions share a common domain unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Confirmed the RS3-scaffolding role in mammalian sperm in vivo and identified a sperm-specific proximal partner essential for motility.\",\n      \"evidence\": \"Cfap91 knockout mice, FLAG-BioID2 proximity labeling, Co-IP, and immunofluorescence in spermatozoa\",\n      \"pmids\": [\"40931011\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct interaction versus proximity for EFCAB5 not distinguished\", \"Structural model of the assembled RS3 scaffold lacking\", \"How CFAP91 coordinates with the central pair complex not detailed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the testis-specific mitochondrial PKA-anchoring function relates mechanistically to the axonemal radial-spoke scaffolding role remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of CFAP91 within the radial spoke\", \"Functional integration of mitochondrial AKAP complex and axonemal scaffolding undefined\", \"Atomic-level basis of partner recruitment unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 3, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [\"calmodulin- and spoke-associated complex (CSC)\", \"radial spoke RS3\", \"AMY-1/AKAP149/PKA-RII quaternary complex\"],\n    \"partners\": [\"WDR66\", \"CFAP251\", \"LRRC23\", \"CCDC39\", \"CFAP206\", \"EFCAB5\", \"AMY-1\", \"AKAP149\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}