{"gene":"CCDC102B","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2018,"finding":"CCDC102B is a centrosome linker protein required for centrosome cohesion. It is recruited to the centrosome by C-Nap1 (CEP250), interacts with centrosome linker components rootletin and LRRC45, decorates and facilitates the formation of rootletin filaments, and is phosphorylated by Nek2A leading to its disassociation from the centrosome at the onset of mitosis.","method":"Co-immunoprecipitation, immunofluorescence localization, in vitro interaction assays, phosphorylation assays, loss-of-function with centrosome cohesion phenotype readout","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, direct localization experiments, multiple orthogonal methods (binding partner identification, PTM identification, functional KD phenotype) in a single focused study","pmids":["30404835"],"is_preprint":false},{"year":2022,"finding":"CCDC102B promotes breast cancer metastasis via activation of the NF-κB pathway. RACK1 promotes CCDC102B lysosomal degradation through chaperone-mediated autophagy (CMA). Loss of RACK1 stabilizes CCDC102B, and overexpressed CCDC102B reduces interaction between RACK1 and IKKα, thereby positively regulating NF-κB pathway activation. CCDC102B and RACK1 interact physically as shown by co-immunoprecipitation and mass spectrometry.","method":"Co-immunoprecipitation, mass spectrometry, CRISPR/Cas9 in vivo screening, RNA sequencing, nuclear protein extraction, immunofluorescence, tail vein metastasis model, subcutaneous xenograft model, wound healing/migration/invasion assays","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with MS confirmation, in vivo models, multiple functional assays, single lab","pmids":["35957886"],"is_preprint":false}],"current_model":"CCDC102B is a centrosome linker protein recruited by C-Nap1 that interacts with rootletin and LRRC45 to facilitate rootletin filament formation and centrosome cohesion during interphase, and is displaced from the centrosome at mitosis onset via Nek2A-mediated phosphorylation; additionally, CCDC102B promotes cancer cell metastasis by interacting with RACK1 to activate the NF-κB pathway, and is itself subject to RACK1-mediated chaperone-mediated autophagy degradation."},"narrative":{"mechanistic_narrative":"CCDC102B is a centrosome linker protein required for centrosome cohesion during interphase [PMID:30404835]. It is recruited to the centrosome by C-Nap1 (CEP250) and interacts with the centrosome linker components rootletin and LRRC45, decorating and facilitating the formation of rootletin filaments; Nek2A-mediated phosphorylation drives its dissociation from the centrosome at the onset of mitosis [PMID:30404835]. Independently, CCDC102B promotes breast cancer metastasis by activating the NF-κB pathway: it physically interacts with RACK1 and reduces the RACK1–IKKα association to potentiate NF-κB activation, while RACK1 in turn targets CCDC102B for lysosomal degradation through chaperone-mediated autophagy [PMID:35957886].","teleology":[{"year":2018,"claim":"Established CCDC102B as a bona fide centrosome linker protein and placed it within the C-Nap1/rootletin cohesion machinery and the Nek2A mitotic disengagement switch, defining its interphase cellular role.","evidence":"Co-IP, immunofluorescence localization, in vitro interaction and phosphorylation assays, and loss-of-function with a centrosome cohesion phenotype readout in cultured cells","pmids":["30404835"],"confidence":"High","gaps":["Structural basis of CCDC102B binding to rootletin/LRRC45 not resolved","Specific Nek2A phosphosite(s) and their direct role in displacement not mapped","Whether CCDC102B is required for rootletin filament nucleation versus stabilization not distinguished"]},{"year":2022,"claim":"Connected CCDC102B to cancer cell behavior by showing it activates NF-κB through RACK1/IKKα modulation and is reciprocally controlled by RACK1-driven chaperone-mediated autophagy, linking its protein stability to a metastatic signaling output.","evidence":"Reciprocal Co-IP with mass spectrometry, CRISPR/Cas9 in vivo screening, RNA-seq, migration/invasion assays, and tail-vein and xenograft mouse models","pmids":["35957886"],"confidence":"Medium","gaps":["Single-lab study; reciprocal validation of the NF-κB axis in independent models pending","Mechanistic link, if any, between the centrosome cohesion role and NF-κB/metastasis function unknown","CMA targeting motif on CCDC102B not defined"]},{"year":null,"claim":"Whether CCDC102B's centrosome-linker function and its RACK1/NF-κB metastatic function are mechanistically coupled remains unresolved.","evidence":"No discovery in the corpus bridges the two functional contexts","pmids":[],"confidence":"Low","gaps":["No experiment tests whether centrosome localization influences NF-κB signaling","No structural or domain-level dissection separating the two activities"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":["centrosome linker"],"partners":["CEP250","ROOTLETIN","LRRC45","NEK2","RACK1","IKKΑ"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q68D86","full_name":"Coiled-coil domain-containing protein 102B","aliases":[],"length_aa":513,"mass_kda":60.4,"function":"During interphase, forms fibers at the proximal ends of centrioles to maintain centrosome cohesion (PubMed:30404835). During mitosis, dissociates from the centrosome following phosphorylation to allow centrosome separation (PubMed:30404835). Contributes to CROCC/rootletin filament formation (PubMed:30404835)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","url":"https://www.uniprot.org/uniprotkb/Q68D86/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCDC102B","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/CCDC102B","total_profiled":1310},"omim":[{"mim_id":"621147","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 102B; CCDC102B","url":"https://www.omim.org/entry/621147"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"placenta","ntpm":26.6}],"url":"https://www.proteinatlas.org/search/CCDC102B"},"hgnc":{"alias_symbol":["FLJ23594","HsT1731","AN"],"prev_symbol":["C18orf14","ACY1L"]},"alphafold":{"accession":"Q68D86","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q68D86","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q68D86-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q68D86-F1-predicted_aligned_error_v6.png","plddt_mean":75.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCDC102B","jax_strain_url":"https://www.jax.org/strain/search?query=CCDC102B"},"sequence":{"accession":"Q68D86","fasta_url":"https://rest.uniprot.org/uniprotkb/Q68D86.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q68D86/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q68D86"}},"corpus_meta":[{"pmid":"27337627","id":"PMC_27337627","title":"Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system.","date":"2016","source":"Forensic science international. 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Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32006895","citation_count":37,"is_preprint":false},{"pmid":"29968770","id":"PMC_29968770","title":"Estimation of chimpanzee age based on DNA methylation.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29968770","citation_count":31,"is_preprint":false},{"pmid":"20358601","id":"PMC_20358601","title":"A maternally inherited chromosome 18q22.1 deletion in a male with late-presenting diaphragmatic hernia and microphthalmia-evaluation of DSEL as a candidate gene for the diaphragmatic defect.","date":"2010","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/20358601","citation_count":30,"is_preprint":false},{"pmid":"31648151","id":"PMC_31648151","title":"Novel multiplex strategy for DNA methylation-based age prediction from small amounts of DNA via Pyrosequencing.","date":"2019","source":"Forensic science international. Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31648151","citation_count":22,"is_preprint":false},{"pmid":"30404835","id":"PMC_30404835","title":"CCDC102B functions in centrosome linker assembly and centrosome cohesion.","date":"2018","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/30404835","citation_count":21,"is_preprint":false},{"pmid":"12118382","id":"PMC_12118382","title":"Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma.","date":"2002","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/12118382","citation_count":19,"is_preprint":false},{"pmid":"33978960","id":"PMC_33978960","title":"Genome-wide identification of age-related CpG sites for age estimation from blood DNA of Han Chinese individuals.","date":"2021","source":"Electrophoresis","url":"https://pubmed.ncbi.nlm.nih.gov/33978960","citation_count":17,"is_preprint":false},{"pmid":"35819508","id":"PMC_35819508","title":"Accurate age estimation from blood samples of Han Chinese individuals using eight high-performance age-related CpG sites.","date":"2022","source":"International journal of legal medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35819508","citation_count":17,"is_preprint":false},{"pmid":"35957886","id":"PMC_35957886","title":"Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35957886","citation_count":11,"is_preprint":false},{"pmid":"37923589","id":"PMC_37923589","title":"DNA methylation-based age estimation and quantification of the degradation levels of bisulfite-converted DNA.","date":"2023","source":"Legal medicine (Tokyo, Japan)","url":"https://pubmed.ncbi.nlm.nih.gov/37923589","citation_count":8,"is_preprint":false},{"pmid":"32730261","id":"PMC_32730261","title":"Genetic and environmental factors related to the development of myopic maculopathy in Spanish patients.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32730261","citation_count":7,"is_preprint":false},{"pmid":"39839508","id":"PMC_39839508","title":"Development and validation of a biomarker-based prediction model for metastasis in patients with colorectal cancer: Application of machine learning algorithms.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/39839508","citation_count":4,"is_preprint":false},{"pmid":"39243524","id":"PMC_39243524","title":"Exploring legal age estimation using DNA methylation.","date":"2024","source":"Forensic science international. 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It is recruited to the centrosome by C-Nap1 (CEP250), interacts with centrosome linker components rootletin and LRRC45, decorates and facilitates the formation of rootletin filaments, and is phosphorylated by Nek2A leading to its disassociation from the centrosome at the onset of mitosis.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence localization, in vitro interaction assays, phosphorylation assays, loss-of-function with centrosome cohesion phenotype readout\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, direct localization experiments, multiple orthogonal methods (binding partner identification, PTM identification, functional KD phenotype) in a single focused study\",\n      \"pmids\": [\"30404835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCDC102B promotes breast cancer metastasis via activation of the NF-κB pathway. RACK1 promotes CCDC102B lysosomal degradation through chaperone-mediated autophagy (CMA). Loss of RACK1 stabilizes CCDC102B, and overexpressed CCDC102B reduces interaction between RACK1 and IKKα, thereby positively regulating NF-κB pathway activation. CCDC102B and RACK1 interact physically as shown by co-immunoprecipitation and mass spectrometry.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, CRISPR/Cas9 in vivo screening, RNA sequencing, nuclear protein extraction, immunofluorescence, tail vein metastasis model, subcutaneous xenograft model, wound healing/migration/invasion assays\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with MS confirmation, in vivo models, multiple functional assays, single lab\",\n      \"pmids\": [\"35957886\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CCDC102B is a centrosome linker protein recruited by C-Nap1 that interacts with rootletin and LRRC45 to facilitate rootletin filament formation and centrosome cohesion during interphase, and is displaced from the centrosome at mitosis onset via Nek2A-mediated phosphorylation; additionally, CCDC102B promotes cancer cell metastasis by interacting with RACK1 to activate the NF-κB pathway, and is itself subject to RACK1-mediated chaperone-mediated autophagy degradation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCDC102B is a centrosome linker protein required for centrosome cohesion during interphase [#0]. It is recruited to the centrosome by C-Nap1 (CEP250) and interacts with the centrosome linker components rootletin and LRRC45, decorating and facilitating the formation of rootletin filaments; Nek2A-mediated phosphorylation drives its dissociation from the centrosome at the onset of mitosis [#0]. Independently, CCDC102B promotes breast cancer metastasis by activating the NF-\\u03baB pathway: it physically interacts with RACK1 and reduces the RACK1\\u2013IKK\\u03b1 association to potentiate NF-\\u03baB activation, while RACK1 in turn targets CCDC102B for lysosomal degradation through chaperone-mediated autophagy [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established CCDC102B as a bona fide centrosome linker protein and placed it within the C-Nap1/rootletin cohesion machinery and the Nek2A mitotic disengagement switch, defining its interphase cellular role.\",\n      \"evidence\": \"Co-IP, immunofluorescence localization, in vitro interaction and phosphorylation assays, and loss-of-function with a centrosome cohesion phenotype readout in cultured cells\",\n      \"pmids\": [\"30404835\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of CCDC102B binding to rootletin/LRRC45 not resolved\",\n        \"Specific Nek2A phosphosite(s) and their direct role in displacement not mapped\",\n        \"Whether CCDC102B is required for rootletin filament nucleation versus stabilization not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected CCDC102B to cancer cell behavior by showing it activates NF-\\u03baB through RACK1/IKK\\u03b1 modulation and is reciprocally controlled by RACK1-driven chaperone-mediated autophagy, linking its protein stability to a metastatic signaling output.\",\n      \"evidence\": \"Reciprocal Co-IP with mass spectrometry, CRISPR/Cas9 in vivo screening, RNA-seq, migration/invasion assays, and tail-vein and xenograft mouse models\",\n      \"pmids\": [\"35957886\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; reciprocal validation of the NF-\\u03baB axis in independent models pending\",\n        \"Mechanistic link, if any, between the centrosome cohesion role and NF-\\u03baB/metastasis function unknown\",\n        \"CMA targeting motif on CCDC102B not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether CCDC102B's centrosome-linker function and its RACK1/NF-\\u03baB metastatic function are mechanistically coupled remains unresolved.\",\n      \"evidence\": \"No discovery in the corpus bridges the two functional contexts\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experiment tests whether centrosome localization influences NF-\\u03baB signaling\",\n        \"No structural or domain-level dissection separating the two activities\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"centrosome linker\"],\n    \"partners\": [\"CEP250\", \"rootletin\", \"LRRC45\", \"NEK2\", \"RACK1\", \"IKK\\u03b1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}