{"gene":"CFAP298","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2022,"finding":"FBB18 (Chlamydomonas ortholog of CFAP298) localizes to the cytoplasm and functions in folding/stabilization of almost all axonemal dynein heavy chains at early steps of dynein preassembly. Mutation causes loss of both outer and inner dynein arms with partial degradation of axonemal dynein heavy chains. FBB18 associates with 9 DNAAFs and 14 out of 15 dynein heavy chains but not with IC1/IC2. FBB18 interacts with RuvBL1/2 (components of HSP90 co-chaperone R2TP complex) but not the holo-R2TP complex.","method":"Comparative proteomics (15N labeling), co-immunoprecipitation/pulldown, subcellular fractionation, Chlamydomonas loss-of-function mutant analysis with electron microscopy of axonemes","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (proteomics, co-IP, fractionation, EM) in a single focused study with defined cellular phenotype","pmids":["36026524"],"is_preprint":false},{"year":2025,"finding":"FBB18 (Chlamydomonas ortholog of CFAP298) adopts a bilobed structure with globular domains at both ends connected by an alpha-helical bundle; one globular domain is structurally homologous to ubiquitin. This ubiquitin-like domain is indispensable for FBB18 molecular function. FBB18 loss reduces stability of dynein heavy chains and disrupts association between heavy chains and intermediate/light chains in the cytoplasm, confirming a cytoplasmic preassembly role for dynein complexes.","method":"X-ray crystallography, Chlamydomonas loss-of-function mutant analysis, biochemical fractionation, domain mutagenesis (ubiquitin-like domain disruption)","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure resolved, mutagenesis of essential domain, and biochemical phenotype in loss-of-function mutant; multiple orthogonal methods in one study","pmids":["40106351"],"is_preprint":false},{"year":2021,"finding":"Loss-of-function of cfap298 (kurly) in zebrafish disrupts cerebrospinal fluid circulation due to defective cilia motility, resulting in three-dimensional spine deformities with orthopedic characteristics (rotational component, right convexity, evolutive during juvenile phase) matching adolescent idiopathic scoliosis criteria.","method":"Zebrafish cfap298tm304 loss-of-function mutant analysis with micro-computed tomography (micro-CT) of the spine","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — defined cellular/organismal phenotype via KO with specific structural readout, single lab, single model organism","pmids":["33795825"],"is_preprint":false},{"year":2025,"finding":"A novel Cfap298 allele (Cfap298ΔΔS/Δ3aa) selectively disrupts left-right axis establishment in mice by impairing cilia motility (tracheal cilia fail to beat) without affecting cilia position, length, or planar cell polarity protein (CELSR1) localization in the node. This mutant fails to rescue LR defects in zebrafish cfap298 (kurly) loss-of-function mutants, identifying a conserved protein region essential for cilia motility.","method":"Mouse knock-in mutant analysis, live cilia imaging (trachea beat assay), immunofluorescence for PCP proteins, zebrafish rescue experiments, Nodal/Pitx2/Lefty1 expression analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (live imaging, rescue genetics, marker expression), two model organisms, single lab; preprint and peer-reviewed versions both available","pmids":["40955177"],"is_preprint":false}],"current_model":"CFAP298 (FBB18 in Chlamydomonas) is a cytoplasmic dynein preassembly factor with a ubiquitin-like domain that is structurally essential for its function; it stabilizes/folds nearly all axonemal dynein heavy chains early in the preassembly pathway by interacting with multiple dynein preassembly factors and dynein heavy chains (but not IC1/IC2) and by associating with the RuvBL1/2 chaperone components, and its loss in vivo causes defective cilia motility, loss of dynein arms, disrupted left-right patterning, and CSF flow abnormalities leading to scoliosis."},"narrative":{"mechanistic_narrative":"CFAP298 is a cytoplasmic axonemal dynein preassembly factor required for the folding and stabilization of axonemal dynein heavy chains, and thereby for the construction of motile cilia [PMID:36026524]. Acting at early steps of the preassembly pathway, it associates with nearly all dynein heavy chains (but not the intermediate chains IC1/IC2) and with multiple dynein assembly factors (DNAAFs), and engages the RuvBL1/RuvBL2 chaperone components without binding the holo-R2TP complex; its loss destabilizes dynein heavy chains and disrupts their cytoplasmic assembly with intermediate and light chains, causing loss of both outer and inner dynein arms [PMID:36026524, PMID:40106351]. Its activity depends on a structurally defined ubiquitin-like domain within a bilobed architecture, mutation of which abolishes function [PMID:40106351]. In vivo, loss of CFAP298 function impairs cilia motility, producing defective left-right axis establishment and disrupted cerebrospinal fluid flow that leads to spine deformities resembling adolescent idiopathic scoliosis [PMID:33795825, PMID:40955177].","teleology":[{"year":2022,"claim":"Established CFAP298 as a cytoplasmic factor acting early in axonemal dynein preassembly rather than within the axoneme itself, defining its molecular role as folding/stabilization of dynein heavy chains.","evidence":"Comparative proteomics, co-IP/pulldown, fractionation and EM of axonemes in a Chlamydomonas FBB18 loss-of-function mutant","pmids":["36026524"],"confidence":"High","gaps":["Does not resolve the structural basis of heavy chain stabilization","Direct versus indirect nature of the many DNAAF/heavy chain associations not dissected","Significance of RuvBL1/2 binding without holo-R2TP unexplained"]},{"year":2021,"claim":"Linked CFAP298 loss to an organismal disease phenotype, showing that defective cilia motility and impaired CSF circulation produce scoliosis-like spine deformities.","evidence":"Zebrafish cfap298 (kurly) loss-of-function mutant analyzed by micro-CT of the spine","pmids":["33795825"],"confidence":"Medium","gaps":["Single model organism and single lab","Mechanistic chain from dynein defect to spine curvature not fully reconstructed"]},{"year":2025,"claim":"Resolved the protein architecture, revealing a bilobed structure with a ubiquitin-like domain that is indispensable for function, and confirmed the cytoplasmic preassembly role through disrupted heavy chain–intermediate/light chain association.","evidence":"X-ray crystallography, ubiquitin-like domain mutagenesis, and biochemical fractionation in Chlamydomonas loss-of-function mutants","pmids":["40106351"],"confidence":"High","gaps":["Molecular mechanism by which the ubiquitin-like domain promotes folding is unknown","Whether the domain mediates protein–protein contacts or a chaperone-like activity not determined"]},{"year":2025,"claim":"Defined a conserved protein region required specifically for cilia motility and left-right patterning, separable from effects on cilia position, length, or planar cell polarity.","evidence":"Mouse knock-in allele with live tracheal cilia imaging, PCP marker IF, Nodal/Pitx2/Lefty1 analysis, and cross-species zebrafish rescue","pmids":["40955177"],"confidence":"Medium","gaps":["Single lab","How the deleted region maps onto the ubiquitin-like domain function is not integrated","Mechanistic link between the region and dynein assembly not established"]},{"year":null,"claim":"How CFAP298 mechanistically stabilizes dynein heavy chains and coordinates with the broader chaperone/DNAAF machinery remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted biochemical assay of the folding/stabilization activity","Functional meaning of RuvBL1/2 association without holo-R2TP unknown","Spectrum of human disease alleles not characterized in this corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0,1]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["RUVBL1","RUVBL2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P57076","full_name":"Cilia- and flagella-associated protein 298","aliases":["Protein kurly homolog"],"length_aa":290,"mass_kda":33.2,"function":"Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly (PubMed:24094744). Seems to be important for initiation rather than maintenance of cilium motility (By similarity). Required for correct positioning of the cilium at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway (By similarity). May suppress canonical Wnt signaling activity (By similarity)","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton, cilium basal body","url":"https://www.uniprot.org/uniprotkb/P57076/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/CFAP298","classification":"Common Essential","n_dependent_lines":1198,"n_total_lines":1208,"dependency_fraction":0.9917218543046358},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000159079","cell_line_id":"CID000385","localizations":[{"compartment":"cytoplasmic","grade":3},{"compartment":"nucleoplasm","grade":3}],"interactors":[{"gene":"JUN","stoichiometry":0.2},{"gene":"C21ORF59","stoichiometry":0.2},{"gene":"ZCCHC3","stoichiometry":0.2},{"gene":"VARS","stoichiometry":0.2},{"gene":"ZC3H4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000385","total_profiled":1310},"omim":[{"mim_id":"615500","title":"CILIARY DYSKINESIA, PRIMARY, 26; CILD26","url":"https://www.omim.org/entry/615500"},{"mim_id":"615494","title":"CILIA- AND FLAGELLA-ASSOCIATED PROTEIN 298; CFAP298","url":"https://www.omim.org/entry/615494"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Basal body","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"},{"location":"Principal piece","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Microtubules","reliability":"Additional"},{"location":"Primary cilium transition zone","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CFAP298"},"hgnc":{"alias_symbol":["FLJ20467","FBB18","CILD26","Kur","DNAAF16"],"prev_symbol":["C21orf48","C21orf59"]},"alphafold":{"accession":"P57076","domains":[{"cath_id":"-","chopping":"3-223","consensus_level":"high","plddt":89.3497,"start":3,"end":223}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P57076","model_url":"https://alphafold.ebi.ac.uk/files/AF-P57076-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P57076-F1-predicted_aligned_error_v6.png","plddt_mean":86.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CFAP298","jax_strain_url":"https://www.jax.org/strain/search?query=CFAP298"},"sequence":{"accession":"P57076","fasta_url":"https://rest.uniprot.org/uniprotkb/P57076.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P57076/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P57076"}},"corpus_meta":[{"pmid":"12382079","id":"PMC_12382079","title":"Electrophysiological and antiarrhythmic effects of the novel I(Kur) channel blockers, S9947 and S20951, on left vs. right pig atrium in vivo in comparison with the I(Kr) blockers dofetilide, azimilide, d,l-sotalol and ibutilide.","date":"2002","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/12382079","citation_count":57,"is_preprint":false},{"pmid":"22409629","id":"PMC_22409629","title":"Discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol-2-yl)-2-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S)-2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone as a potent and selective I(Kur) inhibitor.","date":"2012","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22409629","citation_count":19,"is_preprint":false},{"pmid":"28964116","id":"PMC_28964116","title":"Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity.","date":"2017","source":"Chaos (Woodbury, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/28964116","citation_count":17,"is_preprint":false},{"pmid":"19527375","id":"PMC_19527375","title":"Investigation of beta(2)-adrenoceptor subtype selectivity and organ specificity for bedoradrine (KUR-1246), a novel tocolytic beta-adrenergic receptor stimulant.","date":"2009","source":"The journal of obstetrics and gynaecology research","url":"https://pubmed.ncbi.nlm.nih.gov/19527375","citation_count":14,"is_preprint":false},{"pmid":"36026524","id":"PMC_36026524","title":"FBB18 participates in preassembly of almost all axonemal dyneins independent of R2TP complex.","date":"2022","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36026524","citation_count":11,"is_preprint":false},{"pmid":"33795825","id":"PMC_33795825","title":"The orthopedic characterization of cfap298tm304 mutants validate zebrafish to faithfully model human AIS.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33795825","citation_count":11,"is_preprint":false},{"pmid":"28526291","id":"PMC_28526291","title":"Direct radiocarbon dating and DNA analysis of the Darra-i-Kur (Afghanistan) human temporal bone.","date":"2017","source":"Journal of human evolution","url":"https://pubmed.ncbi.nlm.nih.gov/28526291","citation_count":10,"is_preprint":false},{"pmid":"40106351","id":"PMC_40106351","title":"Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/40106351","citation_count":4,"is_preprint":false},{"pmid":"36605374","id":"PMC_36605374","title":"The Effect of the Tongyang Huoxue Recipe (TYHX) on the I to/I Kur in Ischemia/Reperfusion Sinoatrial Node Cells.","date":"2022","source":"Cardiovascular therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/36605374","citation_count":4,"is_preprint":false},{"pmid":"39966999","id":"PMC_39966999","title":"p300 upregulates I kur in atrial cardiomyocytes through activating NLRP3 inflammasome in hypertension.","date":"2025","source":"Chinese medical journal","url":"https://pubmed.ncbi.nlm.nih.gov/39966999","citation_count":2,"is_preprint":false},{"pmid":"40955177","id":"PMC_40955177","title":"A conserved domain of Cfap298 governs left-right symmetry breaking in vertebrates.","date":"2025","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/40955177","citation_count":1,"is_preprint":false},{"pmid":"19082423","id":"PMC_19082423","title":"[Two-way concentration-dependent effect of H2O2 on I(Kur) and I(Ca,L) in human atrial myocytes.].","date":"2008","source":"Sheng li xue bao : [Acta physiologica Sinica]","url":"https://pubmed.ncbi.nlm.nih.gov/19082423","citation_count":1,"is_preprint":false},{"pmid":"16478001","id":"PMC_16478001","title":"Cardiovascular effects of KUR-1246, a new tetrahydronaphthalen derivative beta2-adrenoceptor agonist and a selective uterine relaxant.","date":"2006","source":"Arzneimittel-Forschung","url":"https://pubmed.ncbi.nlm.nih.gov/16478001","citation_count":1,"is_preprint":false},{"pmid":"40463022","id":"PMC_40463022","title":"A Conserved Domain of Cfap298 Governs Left-Right Symmetry Breaking in Vertebrates.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40463022","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.16.654593","title":"A Conserved Domain of  <i>Cfap298</i>  Governs Left-Right Symmetry Breaking in Vertebrates","date":"2025-05-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.16.654593","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10987,"output_tokens":1338,"usd":0.026516,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7961,"output_tokens":1821,"usd":0.042665,"stage2_stop_reason":"end_turn"},"total_usd":0.069181,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"FBB18 (Chlamydomonas ortholog of CFAP298) localizes to the cytoplasm and functions in folding/stabilization of almost all axonemal dynein heavy chains at early steps of dynein preassembly. Mutation causes loss of both outer and inner dynein arms with partial degradation of axonemal dynein heavy chains. FBB18 associates with 9 DNAAFs and 14 out of 15 dynein heavy chains but not with IC1/IC2. FBB18 interacts with RuvBL1/2 (components of HSP90 co-chaperone R2TP complex) but not the holo-R2TP complex.\",\n      \"method\": \"Comparative proteomics (15N labeling), co-immunoprecipitation/pulldown, subcellular fractionation, Chlamydomonas loss-of-function mutant analysis with electron microscopy of axonemes\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (proteomics, co-IP, fractionation, EM) in a single focused study with defined cellular phenotype\",\n      \"pmids\": [\"36026524\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FBB18 (Chlamydomonas ortholog of CFAP298) adopts a bilobed structure with globular domains at both ends connected by an alpha-helical bundle; one globular domain is structurally homologous to ubiquitin. This ubiquitin-like domain is indispensable for FBB18 molecular function. FBB18 loss reduces stability of dynein heavy chains and disrupts association between heavy chains and intermediate/light chains in the cytoplasm, confirming a cytoplasmic preassembly role for dynein complexes.\",\n      \"method\": \"X-ray crystallography, Chlamydomonas loss-of-function mutant analysis, biochemical fractionation, domain mutagenesis (ubiquitin-like domain disruption)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure resolved, mutagenesis of essential domain, and biochemical phenotype in loss-of-function mutant; multiple orthogonal methods in one study\",\n      \"pmids\": [\"40106351\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Loss-of-function of cfap298 (kurly) in zebrafish disrupts cerebrospinal fluid circulation due to defective cilia motility, resulting in three-dimensional spine deformities with orthopedic characteristics (rotational component, right convexity, evolutive during juvenile phase) matching adolescent idiopathic scoliosis criteria.\",\n      \"method\": \"Zebrafish cfap298tm304 loss-of-function mutant analysis with micro-computed tomography (micro-CT) of the spine\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — defined cellular/organismal phenotype via KO with specific structural readout, single lab, single model organism\",\n      \"pmids\": [\"33795825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A novel Cfap298 allele (Cfap298ΔΔS/Δ3aa) selectively disrupts left-right axis establishment in mice by impairing cilia motility (tracheal cilia fail to beat) without affecting cilia position, length, or planar cell polarity protein (CELSR1) localization in the node. This mutant fails to rescue LR defects in zebrafish cfap298 (kurly) loss-of-function mutants, identifying a conserved protein region essential for cilia motility.\",\n      \"method\": \"Mouse knock-in mutant analysis, live cilia imaging (trachea beat assay), immunofluorescence for PCP proteins, zebrafish rescue experiments, Nodal/Pitx2/Lefty1 expression analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (live imaging, rescue genetics, marker expression), two model organisms, single lab; preprint and peer-reviewed versions both available\",\n      \"pmids\": [\"40955177\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CFAP298 (FBB18 in Chlamydomonas) is a cytoplasmic dynein preassembly factor with a ubiquitin-like domain that is structurally essential for its function; it stabilizes/folds nearly all axonemal dynein heavy chains early in the preassembly pathway by interacting with multiple dynein preassembly factors and dynein heavy chains (but not IC1/IC2) and by associating with the RuvBL1/2 chaperone components, and its loss in vivo causes defective cilia motility, loss of dynein arms, disrupted left-right patterning, and CSF flow abnormalities leading to scoliosis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CFAP298 is a cytoplasmic axonemal dynein preassembly factor required for the folding and stabilization of axonemal dynein heavy chains, and thereby for the construction of motile cilia [#0]. Acting at early steps of the preassembly pathway, it associates with nearly all dynein heavy chains (but not the intermediate chains IC1/IC2) and with multiple dynein assembly factors (DNAAFs), and engages the RuvBL1/RuvBL2 chaperone components without binding the holo-R2TP complex; its loss destabilizes dynein heavy chains and disrupts their cytoplasmic assembly with intermediate and light chains, causing loss of both outer and inner dynein arms [#0, #1]. Its activity depends on a structurally defined ubiquitin-like domain within a bilobed architecture, mutation of which abolishes function [#1]. In vivo, loss of CFAP298 function impairs cilia motility, producing defective left-right axis establishment and disrupted cerebrospinal fluid flow that leads to spine deformities resembling adolescent idiopathic scoliosis [#2, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Established CFAP298 as a cytoplasmic factor acting early in axonemal dynein preassembly rather than within the axoneme itself, defining its molecular role as folding/stabilization of dynein heavy chains.\",\n      \"evidence\": \"Comparative proteomics, co-IP/pulldown, fractionation and EM of axonemes in a Chlamydomonas FBB18 loss-of-function mutant\",\n      \"pmids\": [\"36026524\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not resolve the structural basis of heavy chain stabilization\", \"Direct versus indirect nature of the many DNAAF/heavy chain associations not dissected\", \"Significance of RuvBL1/2 binding without holo-R2TP unexplained\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Linked CFAP298 loss to an organismal disease phenotype, showing that defective cilia motility and impaired CSF circulation produce scoliosis-like spine deformities.\",\n      \"evidence\": \"Zebrafish cfap298 (kurly) loss-of-function mutant analyzed by micro-CT of the spine\",\n      \"pmids\": [\"33795825\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single model organism and single lab\", \"Mechanistic chain from dynein defect to spine curvature not fully reconstructed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolved the protein architecture, revealing a bilobed structure with a ubiquitin-like domain that is indispensable for function, and confirmed the cytoplasmic preassembly role through disrupted heavy chain–intermediate/light chain association.\",\n      \"evidence\": \"X-ray crystallography, ubiquitin-like domain mutagenesis, and biochemical fractionation in Chlamydomonas loss-of-function mutants\",\n      \"pmids\": [\"40106351\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which the ubiquitin-like domain promotes folding is unknown\", \"Whether the domain mediates protein–protein contacts or a chaperone-like activity not determined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a conserved protein region required specifically for cilia motility and left-right patterning, separable from effects on cilia position, length, or planar cell polarity.\",\n      \"evidence\": \"Mouse knock-in allele with live tracheal cilia imaging, PCP marker IF, Nodal/Pitx2/Lefty1 analysis, and cross-species zebrafish rescue\",\n      \"pmids\": [\"40955177\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"How the deleted region maps onto the ubiquitin-like domain function is not integrated\", \"Mechanistic link between the region and dynein assembly not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CFAP298 mechanistically stabilizes dynein heavy chains and coordinates with the broader chaperone/DNAAF machinery remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstituted biochemical assay of the folding/stabilization activity\", \"Functional meaning of RuvBL1/2 association without holo-R2TP unknown\", \"Spectrum of human disease alleles not characterized in this corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RUVBL1\", \"RUVBL2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}