{"gene":"CEP128","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2018,"finding":"CEP128 localizes to the subdistal appendages (SDA) of the mother centriole, and its loss impairs TGF-β/BMP signaling at the primary cilium; mechanistically, loss of CEP128 disrupts ciliary localization of RAB11, consistent with defective vesicle trafficking at the cilium, and quantitative phosphoproteomics showed CEP128 loss affects TGF-β1-induced phosphorylation of multiple proteins regulating cilium-associated vesicle trafficking.","method":"Immunofluorescence localization, siRNA knockdown with signaling assays, zebrafish loss-of-function, quantitative phosphoproteomics","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (localization, KD phenotype, in vivo zebrafish, phosphoproteomics), replicated across mammalian cells and zebrafish","pmids":["29514088"],"is_preprint":false},{"year":2019,"finding":"CEP128 associates with ODF2 at the subdistal appendage of the mother centriole; CEP128 knockdown causes dissociation of other SDA components (centriolin, Ndel1, ninein, CEP170) from the centriole while ODF2 and distal appendage components remain, demonstrating CEP128 acts downstream of ODF2 in hierarchical SDA assembly and is required for centriolar microtubule stability.","method":"Super-resolution structured illumination microscopy (SR-SIM), siRNA knockdown, immunoprecipitation, immunofluorescence of SDA/DA markers","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP establishing ODF2 interaction, SR-SIM localization, KD with defined hierarchical phenotype using multiple markers","pmids":["30623524"],"is_preprint":false},{"year":2022,"finding":"CEP128 is required for spermatogenesis; homozygous knock-in (R222Q) and knockout mice show defective sperm flagella, reduced sperm count, and impaired motility leading to male infertility, while cilia in other organs remain normal, indicating a testis-specific ciliogenesis role; mechanistically, CEP128 regulates expression of spermatogenesis genes and phosphorylation of TGF-β/BMP signaling members during spermatogenesis.","method":"Knock-in and knockout mouse models, sperm morphology/motility analysis, gene expression and phosphorylation profiling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — two independent mouse genetic models (KI and KO) with defined reproductive phenotype and mechanistic signaling data","pmids":["35296684"],"is_preprint":false}],"current_model":"CEP128 is a subdistal appendage protein of the mother centriole that acts downstream of ODF2 in the hierarchical assembly of subdistal appendage components (including centriolin, Ndel1, ninein, and CEP170), stabilizes centriolar microtubules, and is required for proper TGF-β/BMP signaling at the primary cilium via RAB11-dependent vesicle trafficking; in the testis it has an additional cilia-specific role in sperm flagella formation and spermatogenesis, mediated at least in part through regulation of TGF-β/BMP pathway phosphorylation."},"narrative":{"mechanistic_narrative":"CEP128 is a subdistal appendage (SDA) protein of the mother centriole that organizes appendage architecture and links the centriole to ciliary signaling [PMID:29514088, PMID:30623524]. It associates with ODF2 and acts downstream of it in the hierarchical assembly of the SDA: loss of CEP128 dissociates downstream SDA components (centriolin, Ndel1, ninein, and CEP170) from the centriole while ODF2 and distal appendage components remain, and it is required for centriolar microtubule stability [PMID:30623524]. At the primary cilium, CEP128 supports TGF-β/BMP signaling by maintaining ciliary localization of RAB11 and the phosphorylation of proteins controlling cilium-associated vesicle trafficking [PMID:29514088]. In the testis, CEP128 has a tissue-specific ciliogenesis role required for sperm flagella formation and spermatogenesis, mediated in part through regulation of spermatogenesis gene expression and TGF-β/BMP pathway phosphorylation, with loss causing defective flagella, reduced sperm count, impaired motility, and male infertility [PMID:35296684].","teleology":[{"year":2018,"claim":"Established CEP128 as a mother-centriole subdistal appendage protein whose loss disrupts ciliary TGF-β/BMP signaling, linking an appendage component to a signaling output via vesicle trafficking.","evidence":"Immunofluorescence localization, siRNA knockdown signaling assays, zebrafish loss-of-function, and quantitative phosphoproteomics in mammalian cells","pmids":["29514088"],"confidence":"High","gaps":["Direct molecular mechanism connecting CEP128 to RAB11 recruitment not resolved","Identity of the kinase(s)/phosphatase(s) downstream of CEP128 in TGF-β signaling not defined"]},{"year":2019,"claim":"Placed CEP128 in the hierarchy of subdistal appendage assembly, showing it acts downstream of ODF2 to recruit other SDA components and stabilize centriolar microtubules.","evidence":"SR-SIM localization, reciprocal immunoprecipitation with ODF2, and siRNA knockdown scored against multiple SDA/DA markers","pmids":["30623524"],"confidence":"High","gaps":["Structural basis of the CEP128-ODF2 interaction not determined","How CEP128 mechanically stabilizes centriolar microtubules not established"]},{"year":2022,"claim":"Demonstrated an in vivo, tissue-specific requirement for CEP128 in sperm flagella formation and spermatogenesis, distinguishing its testis role from general ciliogenesis.","evidence":"Knock-in (R222Q) and knockout mouse models with sperm morphology/motility analysis and gene expression/phosphorylation profiling","pmids":["35296684"],"confidence":"High","gaps":["Why flagellar defects occur while cilia in other organs remain normal is unexplained","Direct targets linking CEP128 to spermatogenesis gene expression not identified"]},{"year":null,"claim":"How CEP128 mechanistically couples appendage architecture to RAB11-dependent vesicle trafficking and TGF-β/BMP signal transduction remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of CEP128 or its appendage interactions","No defined direct binding partner mediating RAB11 ciliary recruitment","Relationship between SDA assembly defects and signaling defects not causally dissected"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[2]}],"complexes":["subdistal appendage"],"partners":["ODF2","RAB11","CEP170","NIN","NDEL1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6ZU80","full_name":"Centrosomal protein 128","aliases":["Centrosomal protein of 128 kDa"],"length_aa":1094,"mass_kda":128.0,"function":"Is involved in the negative regulation of ciliogenesis and plays a role in spermatogenesis (PubMed:29514088, PubMed:35296684). Contributes to the regulation of the TGFB/BMP signaling pathway at the primary cilium, where it is required for ciliary localization of RAB11A, likely affecting the trafficking and regulation of TGFB/BMP pathway components (PubMed:29514088). Required, together with ODF2, for the formation of the subdistal appendage of the centriole (By similarity)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle pole","url":"https://www.uniprot.org/uniprotkb/Q6ZU80/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP128","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/CEP128","total_profiled":1310},"omim":[{"mim_id":"620667","title":"CENTROSOMAL PROTEIN, 128-KD; CEP128","url":"https://www.omim.org/entry/620667"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":23.1}],"url":"https://www.proteinatlas.org/search/CEP128"},"hgnc":{"alias_symbol":[],"prev_symbol":["C14orf61","C14orf145"]},"alphafold":{"accession":"Q6ZU80","domains":[{"cath_id":"1.20.5","chopping":"981-1019","consensus_level":"medium","plddt":59.4792,"start":981,"end":1019}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZU80","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZU80-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZU80-F1-predicted_aligned_error_v6.png","plddt_mean":74.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP128","jax_strain_url":"https://www.jax.org/strain/search?query=CEP128"},"sequence":{"accession":"Q6ZU80","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZU80.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZU80/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZU80"}},"corpus_meta":[{"pmid":"30134837","id":"PMC_30134837","title":"Circular RNA CEP128 acts as a sponge of miR-145-5p in promoting the bladder cancer progression via regulating SOX11.","date":"2018","source":"Molecular medicine (Cambridge, Mass.)","url":"https://pubmed.ncbi.nlm.nih.gov/30134837","citation_count":80,"is_preprint":false},{"pmid":"29514088","id":"PMC_29514088","title":"CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium.","date":"2018","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29514088","citation_count":61,"is_preprint":false},{"pmid":"30939216","id":"PMC_30939216","title":"Circular RNA CEP128 promotes bladder cancer progression by regulating Mir-145-5p/Myd88 via MAPK signaling pathway.","date":"2019","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30939216","citation_count":58,"is_preprint":false},{"pmid":"35296684","id":"PMC_35296684","title":"CEP128 is involved in spermatogenesis in humans and mice.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35296684","citation_count":44,"is_preprint":false},{"pmid":"30623524","id":"PMC_30623524","title":"Cep128 associates with Odf2 to form the subdistal appendage of the centriole.","date":"2019","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/30623524","citation_count":28,"is_preprint":false},{"pmid":"31599823","id":"PMC_31599823","title":"Knockdown of circular RNA CEP128 suppresses proliferation and improves cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p.","date":"2019","source":"Neuroreport","url":"https://pubmed.ncbi.nlm.nih.gov/31599823","citation_count":28,"is_preprint":false},{"pmid":"35391656","id":"PMC_35391656","title":"Downregulation of Circ-CEP128 Enhances the Paclitaxel Sensitivity of Cervical Cancer Through Regulating miR-432-5p/MCL1.","date":"2022","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35391656","citation_count":12,"is_preprint":false},{"pmid":"30393005","id":"PMC_30393005","title":"CEP128 is a crucial risk locus for autoimmune thyroid diseases.","date":"2018","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/30393005","citation_count":12,"is_preprint":false},{"pmid":"37249021","id":"PMC_37249021","title":"Modulation Effects of the CEP128 Gene on Radiotherapy-Related Brain Injury: A Longitudinal Structural Study Using Multi-Parametric Brain MR Images.","date":"2023","source":"Journal of magnetic resonance imaging : JMRI","url":"https://pubmed.ncbi.nlm.nih.gov/37249021","citation_count":5,"is_preprint":false},{"pmid":"40019841","id":"PMC_40019841","title":"RETRACTION: Circular RNA CEP128 Promotes Bladder Cancer Progression by Regulating Mir-145-5p/Myd88 via MAPK Signaling Pathway.","date":"2025","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/40019841","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7458,"output_tokens":963,"usd":0.018409,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7472,"output_tokens":1743,"usd":0.040468,"stage2_stop_reason":"end_turn"},"total_usd":0.058877,"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\": 2018,\n      \"finding\": \"CEP128 localizes to the subdistal appendages (SDA) of the mother centriole, and its loss impairs TGF-β/BMP signaling at the primary cilium; mechanistically, loss of CEP128 disrupts ciliary localization of RAB11, consistent with defective vesicle trafficking at the cilium, and quantitative phosphoproteomics showed CEP128 loss affects TGF-β1-induced phosphorylation of multiple proteins regulating cilium-associated vesicle trafficking.\",\n      \"method\": \"Immunofluorescence localization, siRNA knockdown with signaling assays, zebrafish loss-of-function, quantitative phosphoproteomics\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (localization, KD phenotype, in vivo zebrafish, phosphoproteomics), replicated across mammalian cells and zebrafish\",\n      \"pmids\": [\"29514088\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CEP128 associates with ODF2 at the subdistal appendage of the mother centriole; CEP128 knockdown causes dissociation of other SDA components (centriolin, Ndel1, ninein, CEP170) from the centriole while ODF2 and distal appendage components remain, demonstrating CEP128 acts downstream of ODF2 in hierarchical SDA assembly and is required for centriolar microtubule stability.\",\n      \"method\": \"Super-resolution structured illumination microscopy (SR-SIM), siRNA knockdown, immunoprecipitation, immunofluorescence of SDA/DA markers\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP establishing ODF2 interaction, SR-SIM localization, KD with defined hierarchical phenotype using multiple markers\",\n      \"pmids\": [\"30623524\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CEP128 is required for spermatogenesis; homozygous knock-in (R222Q) and knockout mice show defective sperm flagella, reduced sperm count, and impaired motility leading to male infertility, while cilia in other organs remain normal, indicating a testis-specific ciliogenesis role; mechanistically, CEP128 regulates expression of spermatogenesis genes and phosphorylation of TGF-β/BMP signaling members during spermatogenesis.\",\n      \"method\": \"Knock-in and knockout mouse models, sperm morphology/motility analysis, gene expression and phosphorylation profiling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two independent mouse genetic models (KI and KO) with defined reproductive phenotype and mechanistic signaling data\",\n      \"pmids\": [\"35296684\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP128 is a subdistal appendage protein of the mother centriole that acts downstream of ODF2 in the hierarchical assembly of subdistal appendage components (including centriolin, Ndel1, ninein, and CEP170), stabilizes centriolar microtubules, and is required for proper TGF-β/BMP signaling at the primary cilium via RAB11-dependent vesicle trafficking; in the testis it has an additional cilia-specific role in sperm flagella formation and spermatogenesis, mediated at least in part through regulation of TGF-β/BMP pathway phosphorylation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP128 is a subdistal appendage (SDA) protein of the mother centriole that organizes appendage architecture and links the centriole to ciliary signaling [#0, #1]. It associates with ODF2 and acts downstream of it in the hierarchical assembly of the SDA: loss of CEP128 dissociates downstream SDA components (centriolin, Ndel1, ninein, and CEP170) from the centriole while ODF2 and distal appendage components remain, and it is required for centriolar microtubule stability [#1]. At the primary cilium, CEP128 supports TGF-\\u03b2/BMP signaling by maintaining ciliary localization of RAB11 and the phosphorylation of proteins controlling cilium-associated vesicle trafficking [#0]. In the testis, CEP128 has a tissue-specific ciliogenesis role required for sperm flagella formation and spermatogenesis, mediated in part through regulation of spermatogenesis gene expression and TGF-\\u03b2/BMP pathway phosphorylation, with loss causing defective flagella, reduced sperm count, impaired motility, and male infertility [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established CEP128 as a mother-centriole subdistal appendage protein whose loss disrupts ciliary TGF-\\u03b2/BMP signaling, linking an appendage component to a signaling output via vesicle trafficking.\",\n      \"evidence\": \"Immunofluorescence localization, siRNA knockdown signaling assays, zebrafish loss-of-function, and quantitative phosphoproteomics in mammalian cells\",\n      \"pmids\": [\"29514088\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct molecular mechanism connecting CEP128 to RAB11 recruitment not resolved\",\n        \"Identity of the kinase(s)/phosphatase(s) downstream of CEP128 in TGF-\\u03b2 signaling not defined\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed CEP128 in the hierarchy of subdistal appendage assembly, showing it acts downstream of ODF2 to recruit other SDA components and stabilize centriolar microtubules.\",\n      \"evidence\": \"SR-SIM localization, reciprocal immunoprecipitation with ODF2, and siRNA knockdown scored against multiple SDA/DA markers\",\n      \"pmids\": [\"30623524\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the CEP128-ODF2 interaction not determined\",\n        \"How CEP128 mechanically stabilizes centriolar microtubules not established\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated an in vivo, tissue-specific requirement for CEP128 in sperm flagella formation and spermatogenesis, distinguishing its testis role from general ciliogenesis.\",\n      \"evidence\": \"Knock-in (R222Q) and knockout mouse models with sperm morphology/motility analysis and gene expression/phosphorylation profiling\",\n      \"pmids\": [\"35296684\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Why flagellar defects occur while cilia in other organs remain normal is unexplained\",\n        \"Direct targets linking CEP128 to spermatogenesis gene expression not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP128 mechanistically couples appendage architecture to RAB11-dependent vesicle trafficking and TGF-\\u03b2/BMP signal transduction remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of CEP128 or its appendage interactions\",\n        \"No defined direct binding partner mediating RAB11 ciliary recruitment\",\n        \"Relationship between SDA assembly defects and signaling defects not causally dissected\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"subdistal appendage\"],\n    \"partners\": [\"ODF2\", \"RAB11\", \"CEP170\", \"NIN\", \"NDEL1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}