{"gene":"CFAP184","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2014,"finding":"CCDC96 (CFAP184) localizes to the centrosome in cultured mammalian cells, as determined by proteomic analysis of sperm centrioles followed by localization assessment.","method":"Mass spectrometry of sperm centrioles; fluorescence localization in cultured cells","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in cultured cells, single lab, single method for CCDC96 specifically","pmids":["25074808"],"is_preprint":false},{"year":2021,"finding":"Ccdc96 (CFAP184) forms a complex with Ccdc113, positioned parallel to the nexin-dynein regulatory complex (N-DRC) and connecting radial spoke 3 (RS3) to dynein g and N-DRC in the ciliary axoneme. Although Ccdc96 and Ccdc113 can be transported to cilia independently, stable docking and function requires both proteins. Deletion of CCDC96 alters cilia beating frequency, amplitude, and waveform, consistent with a role in transmitting regulatory signals from RS3 and N-DRC to dynein g.","method":"Genetic deletion, cryo-electron tomography, co-immunoprecipitation, functional cilia beating assays","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (cryo-ET, co-IP, KO functional assays), mechanistic pathway placement established","pmids":["33661892"],"is_preprint":false},{"year":2023,"finding":"The CCDC96/CCDC113 complex is in close contact with DRC9/10 in the linker region of the N-DRC structure of Tetrahymena thermophila, as revealed by cryo-electron microscopy with biochemical cross-linking and integrative modeling.","method":"Cryo-electron microscopy, biochemical cross-linking, integrative structural modeling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM structure with cross-linking and integrative modeling, peer-reviewed, single study","pmids":["37714832"],"is_preprint":false}],"current_model":"CFAP184 (CCDC96) forms a conserved complex with CCDC113 that localizes to the ciliary axoneme, where it connects radial spoke 3 to dynein g and the nexin-dynein regulatory complex (N-DRC); structural studies place this complex in contact with DRC9/10 in the N-DRC linker region, and loss of either subunit disrupts ciliary beat frequency, amplitude, and waveform, indicating that the complex transmits regulatory signals from RS3/N-DRC to dynein g to coordinate ciliary motility."},"narrative":{"mechanistic_narrative":"CFAP184 (CCDC96) is an axonemal protein that contributes to the structural and regulatory architecture governing ciliary motility [PMID:33661892]. It forms a stable complex with CCDC113 that localizes parallel to the nexin-dynein regulatory complex (N-DRC) in the ciliary axoneme, physically connecting radial spoke 3 (RS3) to dynein g and the N-DRC; while CFAP184 and CCDC113 can each be transported to cilia independently, stable docking and function require both subunits [PMID:33661892]. Structural analysis places this complex in close contact with DRC9/10 in the linker region of the N-DRC [PMID:37714832]. Deletion of CFAP184 alters ciliary beat frequency, amplitude, and waveform, consistent with a role in transmitting regulatory signals from RS3 and the N-DRC to dynein g to coordinate motility [PMID:33661892]. An earlier proteomic and localization study also placed CCDC96 at the centrosome in cultured mammalian cells [PMID:25074808].","teleology":[{"year":2014,"claim":"Established a first subcellular foothold for an uncharacterized coiled-coil protein by identifying it in centriole-associated proteomes, raising the question of its functional role at microtubule-based structures.","evidence":"Mass spectrometry of sperm centrioles with fluorescence localization in cultured mammalian cells","pmids":["25074808"],"confidence":"Medium","gaps":["Single lab, single localization method for CCDC96","No functional role assigned","No binding partners identified"]},{"year":2021,"claim":"Resolved CFAP184's molecular role by showing it forms a CCDC113-dependent complex bridging radial spoke 3 to dynein g and the N-DRC, and that its loss disrupts ciliary beating — establishing it as a regulatory link in the axonemal motility machinery.","evidence":"Genetic deletion, cryo-electron tomography, co-immunoprecipitation, and cilia beating assays","pmids":["33661892"],"confidence":"High","gaps":["Precise mechanism by which the signal is transmitted to dynein g not defined","Stoichiometry of the CFAP184/CCDC113 complex unresolved","How independent transport to cilia is coordinated into stable docking unknown"]},{"year":2023,"claim":"Refined the structural placement of the complex by showing the CCDC96/CCDC113 module contacts DRC9/10 in the N-DRC linker region, anchoring its proposed regulatory connection in molecular detail.","evidence":"Cryo-electron microscopy with biochemical cross-linking and integrative modeling in Tetrahymena thermophila","pmids":["37714832"],"confidence":"High","gaps":["Single study and single organism","Functional consequence of the DRC9/10 contact not tested by perturbation","Atomic-resolution model of the interface not established"]},{"year":null,"claim":"How CFAP184 mechanically transduces RS3/N-DRC regulatory cues into modulation of dynein g activity, and whether its centrosomal localization reflects a distinct non-ciliary function, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No direct demonstration of signal transduction to dynein g activity","Relationship between centrosomal and axonemal localizations unexplained","No human disease association established in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1]},{"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":[1,2]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]}],"pathway":[],"complexes":["CCDC96/CCDC113 complex","N-DRC (associated)"],"partners":["CCDC113","DRC9","DRC10"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q2M329","full_name":"Cilia- and flagella-associated protein 184","aliases":[],"length_aa":555,"mass_kda":62.7,"function":"In complex with CFAP263, acts as a regulator of ciliary beating that connects radial spoke 3 (RS3) to the inner dynein arm (IDA) and the nexin-dynein regulatory complex (N-DRC). The complex is positioned parallel to N-DRC and forms a connection between the arch at the base of RS3, the IDA tail and N-DRC","subcellular_location":"Cell projection, cilium; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q2M329/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CFAP184","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/CFAP184","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"CCDC96","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":61.6}],"url":"https://www.proteinatlas.org/search/CCDC96"},"hgnc":{"alias_symbol":["FLJ90575"],"prev_symbol":["CCDC96"]},"alphafold":{"accession":"Q2M329","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2M329","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q2M329-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q2M329-F1-predicted_aligned_error_v6.png","plddt_mean":67.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CFAP184","jax_strain_url":"https://www.jax.org/strain/search?query=CFAP184"},"sequence":{"accession":"Q2M329","fasta_url":"https://rest.uniprot.org/uniprotkb/Q2M329.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q2M329/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2M329"}},"corpus_meta":[{"pmid":"25074808","id":"PMC_25074808","title":"Proteomic analysis of mammalian sperm cells identifies new components of the centrosome.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/25074808","citation_count":93,"is_preprint":false},{"pmid":"33661892","id":"PMC_33661892","title":"Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link.","date":"2021","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33661892","citation_count":38,"is_preprint":false},{"pmid":"37714832","id":"PMC_37714832","title":"Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37714832","citation_count":29,"is_preprint":false},{"pmid":"37398254","id":"PMC_37398254","title":"Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37398254","citation_count":1,"is_preprint":false},{"pmid":"41214760","id":"PMC_41214760","title":"ZFP36 inhibits the pro-apoptotic effects of transforming growth factor β1 on mitral valve interstitial cells via the GTP-binding protein 6 pathway in mitral valve prolapse.","date":"2025","source":"Experimental physiology","url":"https://pubmed.ncbi.nlm.nih.gov/41214760","citation_count":1,"is_preprint":false},{"pmid":"42200093","id":"PMC_42200093","title":"A novel hsa_circ_0070963/miR-223-3p/ CCDC96-CCDC112 regulatory axis as a non-invasive biomarker for predicting sperm retrieval outcomes in non-obstructive azoospermia: A case-control study.","date":"2026","source":"International journal of reproductive biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/42200093","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5062,"output_tokens":797,"usd":0.01357,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7226,"output_tokens":1610,"usd":0.03819,"stage2_stop_reason":"end_turn"},"total_usd":0.05176,"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\": 2014,\n      \"finding\": \"CCDC96 (CFAP184) localizes to the centrosome in cultured mammalian cells, as determined by proteomic analysis of sperm centrioles followed by localization assessment.\",\n      \"method\": \"Mass spectrometry of sperm centrioles; fluorescence localization in cultured cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in cultured cells, single lab, single method for CCDC96 specifically\",\n      \"pmids\": [\"25074808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Ccdc96 (CFAP184) forms a complex with Ccdc113, positioned parallel to the nexin-dynein regulatory complex (N-DRC) and connecting radial spoke 3 (RS3) to dynein g and N-DRC in the ciliary axoneme. Although Ccdc96 and Ccdc113 can be transported to cilia independently, stable docking and function requires both proteins. Deletion of CCDC96 alters cilia beating frequency, amplitude, and waveform, consistent with a role in transmitting regulatory signals from RS3 and N-DRC to dynein g.\",\n      \"method\": \"Genetic deletion, cryo-electron tomography, co-immunoprecipitation, functional cilia beating assays\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (cryo-ET, co-IP, KO functional assays), mechanistic pathway placement established\",\n      \"pmids\": [\"33661892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The CCDC96/CCDC113 complex is in close contact with DRC9/10 in the linker region of the N-DRC structure of Tetrahymena thermophila, as revealed by cryo-electron microscopy with biochemical cross-linking and integrative modeling.\",\n      \"method\": \"Cryo-electron microscopy, biochemical cross-linking, integrative structural modeling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structure with cross-linking and integrative modeling, peer-reviewed, single study\",\n      \"pmids\": [\"37714832\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CFAP184 (CCDC96) forms a conserved complex with CCDC113 that localizes to the ciliary axoneme, where it connects radial spoke 3 to dynein g and the nexin-dynein regulatory complex (N-DRC); structural studies place this complex in contact with DRC9/10 in the N-DRC linker region, and loss of either subunit disrupts ciliary beat frequency, amplitude, and waveform, indicating that the complex transmits regulatory signals from RS3/N-DRC to dynein g to coordinate ciliary motility.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CFAP184 (CCDC96) is an axonemal protein that contributes to the structural and regulatory architecture governing ciliary motility [#1]. It forms a stable complex with CCDC113 that localizes parallel to the nexin-dynein regulatory complex (N-DRC) in the ciliary axoneme, physically connecting radial spoke 3 (RS3) to dynein g and the N-DRC; while CFAP184 and CCDC113 can each be transported to cilia independently, stable docking and function require both subunits [#1]. Structural analysis places this complex in close contact with DRC9/10 in the linker region of the N-DRC [#2]. Deletion of CFAP184 alters ciliary beat frequency, amplitude, and waveform, consistent with a role in transmitting regulatory signals from RS3 and the N-DRC to dynein g to coordinate motility [#1]. An earlier proteomic and localization study also placed CCDC96 at the centrosome in cultured mammalian cells [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established a first subcellular foothold for an uncharacterized coiled-coil protein by identifying it in centriole-associated proteomes, raising the question of its functional role at microtubule-based structures.\",\n      \"evidence\": \"Mass spectrometry of sperm centrioles with fluorescence localization in cultured mammalian cells\",\n      \"pmids\": [\"25074808\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single lab, single localization method for CCDC96\",\n        \"No functional role assigned\",\n        \"No binding partners identified\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolved CFAP184's molecular role by showing it forms a CCDC113-dependent complex bridging radial spoke 3 to dynein g and the N-DRC, and that its loss disrupts ciliary beating — establishing it as a regulatory link in the axonemal motility machinery.\",\n      \"evidence\": \"Genetic deletion, cryo-electron tomography, co-immunoprecipitation, and cilia beating assays\",\n      \"pmids\": [\"33661892\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Precise mechanism by which the signal is transmitted to dynein g not defined\",\n        \"Stoichiometry of the CFAP184/CCDC113 complex unresolved\",\n        \"How independent transport to cilia is coordinated into stable docking unknown\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Refined the structural placement of the complex by showing the CCDC96/CCDC113 module contacts DRC9/10 in the N-DRC linker region, anchoring its proposed regulatory connection in molecular detail.\",\n      \"evidence\": \"Cryo-electron microscopy with biochemical cross-linking and integrative modeling in Tetrahymena thermophila\",\n      \"pmids\": [\"37714832\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single study and single organism\",\n        \"Functional consequence of the DRC9/10 contact not tested by perturbation\",\n        \"Atomic-resolution model of the interface not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CFAP184 mechanically transduces RS3/N-DRC regulatory cues into modulation of dynein g activity, and whether its centrosomal localization reflects a distinct non-ciliary function, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No direct demonstration of signal transduction to dynein g activity\",\n        \"Relationship between centrosomal and axonemal localizations unexplained\",\n        \"No human disease association established in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"CCDC96/CCDC113 complex\", \"N-DRC (associated)\"],\n    \"partners\": [\"CCDC113\", \"DRC9\", \"DRC10\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}