{"gene":"CCDC116","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2014,"finding":"CCDC116 was identified as a centrosome-associated protein in cultured mammalian cells, localized to the centrosome by mass spectrometry of sperm centrioles followed by assessment of localization in cultured cells.","method":"Mass spectrometry of sperm centrioles; localization assessment in cultured cells (immunofluorescence)","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single localization experiment in one lab, no functional follow-up for CCDC116 specifically","pmids":["25074808"],"is_preprint":false},{"year":2025,"finding":"CCDC116 is recruited to the centrosome downstream of a PLK1-CEP20 signaling axis: PLK1-dependent phosphorylation of CEP20 at Ser46 enables high-affinity CCDC116 binding and centrosomal recruitment, driving centriole overduplication. CCDC116 knockdown abolished centrosomal localization and centrosome amplification.","method":"Phosphorylation site mutagenesis (CEP20-S46A), CCDC116 knockdown, centrosome amplification quantification in human hepatocytes (THLE2/THLE3)","journal":"Journal of agricultural and food chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function (knockdown and phospho-mutant) with defined cellular phenotype (centrosome amplification), single lab, two orthogonal perturbations","pmids":["41401801"],"is_preprint":false},{"year":2025,"finding":"CCDC116 knockdown abolished centrosomal localization (of the CEP20-CCDC116 complex) and prevented centriole overduplication induced by CML (Nε-carboxymethyl-lysine), establishing CCDC116 as a required downstream effector for centrosome amplification in this pathway.","method":"siRNA/shRNA knockdown of CCDC116 in human hepatocytes; centrosome amplification assay","journal":"Journal of agricultural and food chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined KD phenotype (loss of CA), consistent with mutagenesis data in same study, single lab","pmids":["41401801"],"is_preprint":false}],"current_model":"CCDC116 is a centrosome-associated protein that is recruited to the centrosome via direct binding to PLK1-phosphorylated CEP20 (phospho-Ser46), where it promotes centriole overduplication; its knockdown abolishes centrosomal localization and prevents centrosome amplification."},"narrative":{"mechanistic_narrative":"CCDC116 is a centrosome-associated protein that functions as a downstream effector promoting centriole overduplication [PMID:25074808, PMID:41401801]. It is recruited to the centrosome through a PLK1–CEP20 signaling axis: PLK1-dependent phosphorylation of CEP20 at Ser46 generates a high-affinity binding site for CCDC116, and a phospho-deficient CEP20-S46A mutant fails to support this recruitment [PMID:41401801]. Knockdown of CCDC116 abolishes centrosomal localization of the CEP20–CCDC116 complex and prevents centrosome amplification, including the overduplication driven by Nε-carboxymethyl-lysine (CML) exposure in human hepatocytes, establishing CCDC116 as a required effector for centriole overduplication in this pathway [PMID:41401801]. Beyond its recruitment by phospho-CEP20 and its requirement for centrosome amplification, no biochemical activity or structural detail for CCDC116 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Established CCDC116 as a centrosome-associated protein, placing an otherwise uncharacterized protein at a defined subcellular structure and motivating a centriole-related function.","evidence":"Mass spectrometry of sperm centrioles with immunofluorescence localization in cultured mammalian cells","pmids":["25074808"],"confidence":"Medium","gaps":["Single localization experiment with no functional follow-up","No interacting partners or recruitment mechanism identified","No molecular activity assigned"]},{"year":2025,"claim":"Defined how CCDC116 reaches the centrosome and what it does there, showing PLK1-phosphorylated CEP20 (phospho-Ser46) recruits CCDC116 to drive centriole overduplication.","evidence":"CEP20-S46A phospho-mutant and CCDC116 knockdown with centrosome amplification quantification in human hepatocytes (THLE2/THLE3)","pmids":["41401801"],"confidence":"Medium","gaps":["Direct CCDC116–CEP20 binding affinity and stoichiometry not structurally resolved","Biochemical activity of CCDC116 itself unknown","Findings from a single lab"]},{"year":2025,"claim":"Showed CCDC116 is a required downstream effector by demonstrating its loss blocks CML-induced centrosome amplification, linking the recruitment axis to a defined upstream stimulus.","evidence":"siRNA/shRNA knockdown of CCDC116 in human hepatocytes with centrosome amplification assay under CML treatment","pmids":["41401801"],"confidence":"Medium","gaps":["Molecular mechanism by which CCDC116 promotes overduplication is undefined","Whether the requirement generalizes beyond the CML/hepatocyte context is untested","No reciprocal validation of complex composition in an independent system"]},{"year":null,"claim":"The intrinsic biochemical activity of CCDC116 and how its centrosomal recruitment mechanistically triggers centriole overduplication remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No enzymatic or structural function assigned to CCDC116","Downstream effectors engaged by centrosomal CCDC116 unknown","No structural model of the phospho-CEP20–CCDC116 interface"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1,2]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["CEP20"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IYX3","full_name":"Coiled-coil domain-containing protein 116","aliases":[],"length_aa":613,"mass_kda":67.9,"function":"","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q8IYX3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCDC116","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CCDC116","total_profiled":1310},"omim":[{"mim_id":"616070","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 113; CCDC113","url":"https://www.omim.org/entry/616070"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":28.5}],"url":"https://www.proteinatlas.org/search/CCDC116"},"hgnc":{"alias_symbol":["FLJ36046"],"prev_symbol":[]},"alphafold":{"accession":"Q8IYX3","domains":[{"cath_id":"-","chopping":"430-516","consensus_level":"medium","plddt":71.5613,"start":430,"end":516}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IYX3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IYX3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IYX3-F1-predicted_aligned_error_v6.png","plddt_mean":49.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCDC116","jax_strain_url":"https://www.jax.org/strain/search?query=CCDC116"},"sequence":{"accession":"Q8IYX3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IYX3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IYX3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IYX3"}},"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":"29193083","id":"PMC_29193083","title":"Integrating expression-related SNPs into genome-wide gene- and pathway-based analyses identified novel lung cancer susceptibility genes.","date":"2017","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29193083","citation_count":16,"is_preprint":false},{"pmid":"23072936","id":"PMC_23072936","title":"Expression of the coiled coil domain containing protein 116 in the pancreatic islets and endocrine pancreatic tumors.","date":"2012","source":"Islets","url":"https://pubmed.ncbi.nlm.nih.gov/23072936","citation_count":8,"is_preprint":false},{"pmid":"28653172","id":"PMC_28653172","title":"A cis-eQTL genetic variant of the cancer-testis gene CCDC116 is associated with risk of multiple cancers.","date":"2017","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28653172","citation_count":7,"is_preprint":false},{"pmid":"41581221","id":"PMC_41581221","title":"Identifying expression and DNA methylation biomarkers for lung adenocarcinoma risk in East Asia.","date":"2026","source":"Journal of the National Cancer Institute","url":"https://pubmed.ncbi.nlm.nih.gov/41581221","citation_count":2,"is_preprint":false},{"pmid":"41401801","id":"PMC_41401801","title":"Nε-Carboxymethyl-Lysine Drives Centrosome Amplification and Hepatocarcinogenesis via Pathological Dysregulation of the PLK1-CEP20-CCDC116 Axis.","date":"2025","source":"Journal of agricultural and food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41401801","citation_count":0,"is_preprint":false},{"pmid":"41878161","id":"PMC_41878161","title":"Single-cell and multi-omics analyses identify CAMP-associated neutrophil remodeling during radiochemotherapy in cervical cancer.","date":"2026","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/41878161","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5953,"output_tokens":764,"usd":0.01466,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7162,"output_tokens":1520,"usd":0.036905,"stage2_stop_reason":"end_turn"},"total_usd":0.051565,"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\": \"CCDC116 was identified as a centrosome-associated protein in cultured mammalian cells, localized to the centrosome by mass spectrometry of sperm centrioles followed by assessment of localization in cultured cells.\",\n      \"method\": \"Mass spectrometry of sperm centrioles; localization assessment in cultured cells (immunofluorescence)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization experiment in one lab, no functional follow-up for CCDC116 specifically\",\n      \"pmids\": [\"25074808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CCDC116 is recruited to the centrosome downstream of a PLK1-CEP20 signaling axis: PLK1-dependent phosphorylation of CEP20 at Ser46 enables high-affinity CCDC116 binding and centrosomal recruitment, driving centriole overduplication. CCDC116 knockdown abolished centrosomal localization and centrosome amplification.\",\n      \"method\": \"Phosphorylation site mutagenesis (CEP20-S46A), CCDC116 knockdown, centrosome amplification quantification in human hepatocytes (THLE2/THLE3)\",\n      \"journal\": \"Journal of agricultural and food chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function (knockdown and phospho-mutant) with defined cellular phenotype (centrosome amplification), single lab, two orthogonal perturbations\",\n      \"pmids\": [\"41401801\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CCDC116 knockdown abolished centrosomal localization (of the CEP20-CCDC116 complex) and prevented centriole overduplication induced by CML (Nε-carboxymethyl-lysine), establishing CCDC116 as a required downstream effector for centrosome amplification in this pathway.\",\n      \"method\": \"siRNA/shRNA knockdown of CCDC116 in human hepatocytes; centrosome amplification assay\",\n      \"journal\": \"Journal of agricultural and food chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined KD phenotype (loss of CA), consistent with mutagenesis data in same study, single lab\",\n      \"pmids\": [\"41401801\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CCDC116 is a centrosome-associated protein that is recruited to the centrosome via direct binding to PLK1-phosphorylated CEP20 (phospho-Ser46), where it promotes centriole overduplication; its knockdown abolishes centrosomal localization and prevents centrosome amplification.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCDC116 is a centrosome-associated protein that functions as a downstream effector promoting centriole overduplication [#0, #1]. It is recruited to the centrosome through a PLK1–CEP20 signaling axis: PLK1-dependent phosphorylation of CEP20 at Ser46 generates a high-affinity binding site for CCDC116, and a phospho-deficient CEP20-S46A mutant fails to support this recruitment [#1]. Knockdown of CCDC116 abolishes centrosomal localization of the CEP20–CCDC116 complex and prevents centrosome amplification, including the overduplication driven by Nε-carboxymethyl-lysine (CML) exposure in human hepatocytes, establishing CCDC116 as a required effector for centriole overduplication in this pathway [#1, #2]. Beyond its recruitment by phospho-CEP20 and its requirement for centrosome amplification, no biochemical activity or structural detail for CCDC116 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established CCDC116 as a centrosome-associated protein, placing an otherwise uncharacterized protein at a defined subcellular structure and motivating a centriole-related function.\",\n      \"evidence\": \"Mass spectrometry of sperm centrioles with immunofluorescence localization in cultured mammalian cells\",\n      \"pmids\": [\n        \"25074808\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single localization experiment with no functional follow-up\",\n        \"No interacting partners or recruitment mechanism identified\",\n        \"No molecular activity assigned\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined how CCDC116 reaches the centrosome and what it does there, showing PLK1-phosphorylated CEP20 (phospho-Ser46) recruits CCDC116 to drive centriole overduplication.\",\n      \"evidence\": \"CEP20-S46A phospho-mutant and CCDC116 knockdown with centrosome amplification quantification in human hepatocytes (THLE2/THLE3)\",\n      \"pmids\": [\n        \"41401801\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct CCDC116–CEP20 binding affinity and stoichiometry not structurally resolved\",\n        \"Biochemical activity of CCDC116 itself unknown\",\n        \"Findings from a single lab\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed CCDC116 is a required downstream effector by demonstrating its loss blocks CML-induced centrosome amplification, linking the recruitment axis to a defined upstream stimulus.\",\n      \"evidence\": \"siRNA/shRNA knockdown of CCDC116 in human hepatocytes with centrosome amplification assay under CML treatment\",\n      \"pmids\": [\n        \"41401801\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism by which CCDC116 promotes overduplication is undefined\",\n        \"Whether the requirement generalizes beyond the CML/hepatocyte context is untested\",\n        \"No reciprocal validation of complex composition in an independent system\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic biochemical activity of CCDC116 and how its centrosomal recruitment mechanistically triggers centriole overduplication remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No enzymatic or structural function assigned to CCDC116\",\n        \"Downstream effectors engaged by centrosomal CCDC116 unknown\",\n        \"No structural model of the phospho-CEP20–CCDC116 interface\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005815\",\n        \"supporting_discovery_ids\": [\n          0,\n          1,\n          2\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1640170\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"CEP20\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}