{"gene":"EFCAB10","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2025,"finding":"EFCAB10 is a radial spoke protein in motile cilia that anchors adenylate kinase AK8 to the radial spoke; loss of EFCAB10 results in complete absence of ciliary AK8, whereas loss of AK8 has no effect on ciliary EFCAB10, establishing a unidirectional dependency.","method":"Knockout mouse models (Efcab10 and Ak8 null mice), ciliary localization analysis, and biochemical interaction studies showing EFCAB10 interacts with AK8 and RSPH3B","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic epistasis via two knockout models combined with biochemical co-interaction and localization data in a single rigorous study","pmids":["41055978"],"is_preprint":false},{"year":2025,"finding":"EFCAB10 physically interacts with RSPH3B as part of the radial spoke complex, contributing to the structural integrity of the radial spoke.","method":"Biochemical interaction analyses (co-immunoprecipitation/pulldown) in mouse cilia","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, biochemical interaction data reported without full reconstitution or structural validation","pmids":["41055978"],"is_preprint":false},{"year":2025,"finding":"Loss of EFCAB10 disrupts ciliary motility and causes primary ciliary dyskinesia (PCD)-related phenotypes including respiratory defects and infertility in mice, demonstrating its essential role in motile cilia function.","method":"Efcab10 knockout mouse model with ciliary motility measurements and phenotypic analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout with defined cellular and physiological phenotypes, corroborated by parallel Ak8 knockout and epistasis analysis","pmids":["41055978"],"is_preprint":false}],"current_model":"EFCAB10 is a radial spoke protein in motile cilia that directly interacts with AK8 and RSPH3B to anchor AK8 to the radial spoke, maintaining radial spoke structural integrity and proper ciliary motility; loss of EFCAB10 abolishes ciliary AK8 and causes primary ciliary dyskinesia-like phenotypes in mice."},"narrative":{"mechanistic_narrative":"EFCAB10 is a radial spoke protein of motile cilia that maintains ciliary motility by anchoring the adenylate kinase AK8 to the radial spoke [PMID:41055978]. It physically interacts with both AK8 and the radial spoke component RSPH3B, contributing to the structural integrity of the radial spoke complex [PMID:41055978]. The dependency is unidirectional: loss of EFCAB10 completely abolishes ciliary AK8, whereas loss of AK8 does not affect EFCAB10 localization, establishing EFCAB10 as the anchoring partner rather than the cargo [PMID:41055978]. Consistent with this role, Efcab10 knockout mice display disrupted ciliary motility and primary ciliary dyskinesia-related phenotypes including respiratory defects and infertility [PMID:41055978]. Beyond its radial spoke anchoring function defined in these mouse studies, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether EFCAB10 had a defined role in cilia was unknown; knockout mouse studies established it as a radial spoke protein that anchors AK8 and is required for motile cilia function, defining a directional anchoring relationship.","evidence":"Efcab10 and Ak8 knockout mouse models with ciliary localization analysis showing complete loss of ciliary AK8 upon EFCAB10 loss but no reciprocal effect","pmids":["41055978"],"confidence":"High","gaps":["Molecular basis of how EFCAB10 tethers AK8 to the spoke is undefined","No structural model of the EFCAB10-AK8-RSPH3B assembly","Functional consequence of AK8 loss on local nucleotide handling within cilia not established"]},{"year":2025,"claim":"How EFCAB10 integrates into the radial spoke was unclear; biochemical interaction with RSPH3B placed it physically within the radial spoke complex.","evidence":"Co-immunoprecipitation/pulldown in mouse cilia demonstrating EFCAB10-RSPH3B interaction","pmids":["41055978"],"confidence":"Medium","gaps":["Interaction reported from a single lab without reconstitution or structural validation","Stoichiometry and binding interface within the radial spoke unknown","Whether RSPH3B binding is required for AK8 anchoring not dissected"]},{"year":2025,"claim":"The physiological importance of EFCAB10 was untested; knockout mice linked its loss to ciliary motility defects and PCD-like disease phenotypes.","evidence":"Efcab10 knockout mouse with ciliary motility measurements and phenotypic analysis of respiratory defects and infertility","pmids":["41055978"],"confidence":"High","gaps":["No human PCD patients with EFCAB10 mutations reported in the corpus","Mechanistic link between AK8 mislocalization and motility failure not directly demonstrated"]},{"year":null,"claim":"Whether EFCAB10 mutations cause primary ciliary dyskinesia in humans, and the structural mechanism by which it tethers AK8 to the radial spoke, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No human genetic evidence in the corpus","No high-resolution structure of the anchoring complex","Role of EFCAB10 EF-hand/calcium binding in function untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,2]}],"pathway":[],"complexes":["radial spoke"],"partners":["AK8","RSPH3B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A6NFE3","full_name":"EF-hand calcium-binding domain-containing protein 10","aliases":[],"length_aa":127,"mass_kda":14.7,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/A6NFE3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EFCAB10","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":73,"dependency_fraction":0.0136986301369863},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/EFCAB10","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"choroid plexus","ntpm":12.0},{"tissue":"fallopian tube","ntpm":27.9},{"tissue":"testis","ntpm":22.0}],"url":"https://www.proteinatlas.org/search/EFCAB10"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"A6NFE3","domains":[{"cath_id":"1.20.890","chopping":"2-56","consensus_level":"high","plddt":87.8904,"start":2,"end":56},{"cath_id":"1.10.238","chopping":"66-127","consensus_level":"high","plddt":83.6273,"start":66,"end":127}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NFE3","model_url":"https://alphafold.ebi.ac.uk/files/AF-A6NFE3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A6NFE3-F1-predicted_aligned_error_v6.png","plddt_mean":83.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EFCAB10","jax_strain_url":"https://www.jax.org/strain/search?query=EFCAB10"},"sequence":{"accession":"A6NFE3","fasta_url":"https://rest.uniprot.org/uniprotkb/A6NFE3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A6NFE3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NFE3"}},"corpus_meta":[{"pmid":"41055978","id":"PMC_41055978","title":"EFCAB10 anchors AK8 to the radial spoke for proper ciliary motility.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/41055978","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2679,"output_tokens":730,"usd":0.009494,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7147,"output_tokens":1480,"usd":0.036367,"stage2_stop_reason":"end_turn"},"total_usd":0.045861,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"EFCAB10 is a radial spoke protein in motile cilia that anchors adenylate kinase AK8 to the radial spoke; loss of EFCAB10 results in complete absence of ciliary AK8, whereas loss of AK8 has no effect on ciliary EFCAB10, establishing a unidirectional dependency.\",\n      \"method\": \"Knockout mouse models (Efcab10 and Ak8 null mice), ciliary localization analysis, and biochemical interaction studies showing EFCAB10 interacts with AK8 and RSPH3B\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic epistasis via two knockout models combined with biochemical co-interaction and localization data in a single rigorous study\",\n      \"pmids\": [\"41055978\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"EFCAB10 physically interacts with RSPH3B as part of the radial spoke complex, contributing to the structural integrity of the radial spoke.\",\n      \"method\": \"Biochemical interaction analyses (co-immunoprecipitation/pulldown) in mouse cilia\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, biochemical interaction data reported without full reconstitution or structural validation\",\n      \"pmids\": [\"41055978\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of EFCAB10 disrupts ciliary motility and causes primary ciliary dyskinesia (PCD)-related phenotypes including respiratory defects and infertility in mice, demonstrating its essential role in motile cilia function.\",\n      \"method\": \"Efcab10 knockout mouse model with ciliary motility measurements and phenotypic analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout with defined cellular and physiological phenotypes, corroborated by parallel Ak8 knockout and epistasis analysis\",\n      \"pmids\": [\"41055978\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EFCAB10 is a radial spoke protein in motile cilia that directly interacts with AK8 and RSPH3B to anchor AK8 to the radial spoke, maintaining radial spoke structural integrity and proper ciliary motility; loss of EFCAB10 abolishes ciliary AK8 and causes primary ciliary dyskinesia-like phenotypes in mice.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EFCAB10 is a radial spoke protein of motile cilia that maintains ciliary motility by anchoring the adenylate kinase AK8 to the radial spoke [#0]. It physically interacts with both AK8 and the radial spoke component RSPH3B, contributing to the structural integrity of the radial spoke complex [#0, #1]. The dependency is unidirectional: loss of EFCAB10 completely abolishes ciliary AK8, whereas loss of AK8 does not affect EFCAB10 localization, establishing EFCAB10 as the anchoring partner rather than the cargo [#0]. Consistent with this role, Efcab10 knockout mice display disrupted ciliary motility and primary ciliary dyskinesia-related phenotypes including respiratory defects and infertility [#2]. Beyond its radial spoke anchoring function defined in these mouse studies, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether EFCAB10 had a defined role in cilia was unknown; knockout mouse studies established it as a radial spoke protein that anchors AK8 and is required for motile cilia function, defining a directional anchoring relationship.\",\n      \"evidence\": \"Efcab10 and Ak8 knockout mouse models with ciliary localization analysis showing complete loss of ciliary AK8 upon EFCAB10 loss but no reciprocal effect\",\n      \"pmids\": [\"41055978\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of how EFCAB10 tethers AK8 to the spoke is undefined\", \"No structural model of the EFCAB10-AK8-RSPH3B assembly\", \"Functional consequence of AK8 loss on local nucleotide handling within cilia not established\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"How EFCAB10 integrates into the radial spoke was unclear; biochemical interaction with RSPH3B placed it physically within the radial spoke complex.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown in mouse cilia demonstrating EFCAB10-RSPH3B interaction\",\n      \"pmids\": [\"41055978\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction reported from a single lab without reconstitution or structural validation\", \"Stoichiometry and binding interface within the radial spoke unknown\", \"Whether RSPH3B binding is required for AK8 anchoring not dissected\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The physiological importance of EFCAB10 was untested; knockout mice linked its loss to ciliary motility defects and PCD-like disease phenotypes.\",\n      \"evidence\": \"Efcab10 knockout mouse with ciliary motility measurements and phenotypic analysis of respiratory defects and infertility\",\n      \"pmids\": [\"41055978\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No human PCD patients with EFCAB10 mutations reported in the corpus\", \"Mechanistic link between AK8 mislocalization and motility failure not directly demonstrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether EFCAB10 mutations cause primary ciliary dyskinesia in humans, and the structural mechanism by which it tethers AK8 to the radial spoke, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No human genetic evidence in the corpus\", \"No high-resolution structure of the anchoring complex\", \"Role of EFCAB10 EF-hand/calcium binding in function untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"radial spoke\"],\n    \"partners\": [\"AK8\", \"RSPH3B\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}