{"gene":"CCDC77","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2025,"finding":"CCDC77 localizes to the A-C linker structure of centrioles, positioned between microtubule triplets in the proximal region, where it forms a complex with WDR67 and MIIP. Depletion of CCDC77 (along with other A-C linker components) disrupts microtubule triplet cohesion, causing breakage at the proximal end of the centriole. Co-removal of the A-C linker and the inner scaffold reveals their joint role in maintaining centriole architecture. Additionally, the A-C linker (including CCDC77) plays an unexpected role in centriole duplication through torus regulation.","method":"Ultrastructure expansion microscopy (U-ExM), protein depletion (knockdown/knockout), co-localization and complex formation analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization by expansion microscopy with functional consequence (depletion phenotype), complex formation demonstrated, replicated across preprint and peer-reviewed publication from same lab with multiple orthogonal methods","pmids":["40707486"],"is_preprint":false},{"year":2024,"finding":"CCDC77 localizes to the A-C linker of centrioles between microtubule triplets, forming a complex with WDR67 and MIIP; depletion of A-C linker components disrupts triplet cohesion and centriole duplication via torus regulation (preprint version of the same study).","method":"Ultrastructure expansion microscopy, protein depletion, complex formation analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — same findings as published paper but preprint status; multiple orthogonal methods in single lab","pmids":["bio_10.1101_2024.10.04.616628"],"is_preprint":true}],"current_model":"CCDC77 is an A-C linker protein in centrioles that localizes between adjacent microtubule triplets in the proximal region, forms a complex with WDR67 and MIIP, and is required for microtubule triplet cohesion, centriole structural integrity, and centriole duplication through regulation of the torus."},"narrative":{"mechanistic_narrative":"CCDC77 is a structural component of the centriole A-C linker, a connector positioned between adjacent microtubule triplets in the proximal region of the organelle [PMID:40707486]. Within this structure CCDC77 assembles into a complex with WDR67 and MIIP, and its depletion disrupts microtubule triplet cohesion, causing breakage at the proximal end of the centriole; combined removal of the A-C linker and the inner scaffold demonstrates their joint requirement for maintaining overall centriole architecture [PMID:40707486]. Beyond its structural role, the A-C linker including CCDC77 contributes to centriole duplication through regulation of the torus [PMID:40707486]. Beyond these findings, no further mechanistic detail for CCDC77 has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Established where CCDC77 sits in centriole ultrastructure and what it binds, addressing whether this uncharacterized coiled-coil protein has a defined structural role at the centriole.","evidence":"Ultrastructure expansion microscopy, protein depletion, and complex-formation analysis (preprint)","pmids":["bio_10.1101_2024.10.04.616628"],"confidence":"Medium","gaps":["Preprint version, not yet peer reviewed","Stoichiometry and direct binding interfaces within the WDR67/MIIP complex not resolved","Molecular basis of torus regulation in duplication unexplained"]},{"year":2025,"claim":"Confirmed CCDC77 as an A-C linker protein between microtubule triplets that, in complex with WDR67 and MIIP, is required for triplet cohesion, centriole integrity, and duplication via the torus, establishing its function in maintaining centriole architecture.","evidence":"U-ExM, knockdown/knockout depletion with phenotyping, co-localization and complex formation analysis in cultured cells","pmids":["40707486"],"confidence":"High","gaps":["Mechanism by which the A-C linker regulates the torus during duplication unresolved","No structure of the CCDC77–WDR67–MIIP complex","Direct versus indirect contributions of CCDC77 to cohesion not separated from other A-C linker components"]},{"year":null,"claim":"How CCDC77 mechanistically couples A-C linker integrity to torus-dependent centriole duplication remains unknown.","evidence":"","pmids":[],"confidence":"High","gaps":["No biochemical reconstitution of the complex","No structural model of the A-C linker","Recruitment hierarchy among CCDC77, WDR67, and MIIP undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":["CCDC77-WDR67-MIIP A-C linker complex"],"partners":["WDR67","MIIP"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BR77","full_name":"Coiled-coil domain-containing protein 77","aliases":[],"length_aa":488,"mass_kda":57.5,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9BR77/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCDC77","classification":"Not Classified","n_dependent_lines":31,"n_total_lines":1208,"dependency_fraction":0.02566225165562914},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CCDC77","total_profiled":1310},"omim":[{"mim_id":"621444","title":"TBC1 DOMAIN FAMILY, MEMBER 31; TBC1D31","url":"https://www.omim.org/entry/621444"},{"mim_id":"608772","title":"MIGRATION AND INVASION INHIBITORY PROTEIN; MIIP","url":"https://www.omim.org/entry/608772"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear membrane","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CCDC77"},"hgnc":{"alias_symbol":["MGC13183"],"prev_symbol":[]},"alphafold":{"accession":"Q9BR77","domains":[{"cath_id":"-","chopping":"61-151_221-326_347-487","consensus_level":"medium","plddt":91.3735,"start":61,"end":487}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BR77","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BR77-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BR77-F1-predicted_aligned_error_v6.png","plddt_mean":79.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCDC77","jax_strain_url":"https://www.jax.org/strain/search?query=CCDC77"},"sequence":{"accession":"Q9BR77","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BR77.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BR77/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BR77"}},"corpus_meta":[{"pmid":"24613754","id":"PMC_24613754","title":"A 1.5Mb terminal deletion of 12p associated with autism spectrum disorder.","date":"2014","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/24613754","citation_count":20,"is_preprint":false},{"pmid":"38812741","id":"PMC_38812741","title":"Integration of Multi-Omics Data for the Classification of Glioma Types and Identification of Novel Biomarkers.","date":"2024","source":"Bioinformatics and biology insights","url":"https://pubmed.ncbi.nlm.nih.gov/38812741","citation_count":11,"is_preprint":false},{"pmid":"40707486","id":"PMC_40707486","title":"The A-C linker controls centriole structural integrity and duplication.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40707486","citation_count":10,"is_preprint":false},{"pmid":"42239780","id":"PMC_42239780","title":"Identification of novel candidate neural genes for diet-induced obesity in outbred heterogeneous stock rats.","date":"2026","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/42239780","citation_count":0,"is_preprint":false},{"pmid":"41074104","id":"PMC_41074104","title":"Saliva as a potential and non-invasive approach to identify upregulated genes associated with comorbidities of T1DM: a brief report.","date":"2025","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/41074104","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.10.04.616628","title":"The A-C Linker controls centriole cohesion and duplication","date":"2024-10-04","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.04.616628","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5356,"output_tokens":625,"usd":0.012722,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6936,"output_tokens":1277,"usd":0.033302,"stage2_stop_reason":"end_turn"},"total_usd":0.046024,"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\": 2025,\n      \"finding\": \"CCDC77 localizes to the A-C linker structure of centrioles, positioned between microtubule triplets in the proximal region, where it forms a complex with WDR67 and MIIP. Depletion of CCDC77 (along with other A-C linker components) disrupts microtubule triplet cohesion, causing breakage at the proximal end of the centriole. Co-removal of the A-C linker and the inner scaffold reveals their joint role in maintaining centriole architecture. Additionally, the A-C linker (including CCDC77) plays an unexpected role in centriole duplication through torus regulation.\",\n      \"method\": \"Ultrastructure expansion microscopy (U-ExM), protein depletion (knockdown/knockout), co-localization and complex formation analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization by expansion microscopy with functional consequence (depletion phenotype), complex formation demonstrated, replicated across preprint and peer-reviewed publication from same lab with multiple orthogonal methods\",\n      \"pmids\": [\"40707486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CCDC77 localizes to the A-C linker of centrioles between microtubule triplets, forming a complex with WDR67 and MIIP; depletion of A-C linker components disrupts triplet cohesion and centriole duplication via torus regulation (preprint version of the same study).\",\n      \"method\": \"Ultrastructure expansion microscopy, protein depletion, complex formation analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — same findings as published paper but preprint status; multiple orthogonal methods in single lab\",\n      \"pmids\": [\"bio_10.1101_2024.10.04.616628\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CCDC77 is an A-C linker protein in centrioles that localizes between adjacent microtubule triplets in the proximal region, forms a complex with WDR67 and MIIP, and is required for microtubule triplet cohesion, centriole structural integrity, and centriole duplication through regulation of the torus.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCDC77 is a structural component of the centriole A-C linker, a connector positioned between adjacent microtubule triplets in the proximal region of the organelle [#0]. Within this structure CCDC77 assembles into a complex with WDR67 and MIIP, and its depletion disrupts microtubule triplet cohesion, causing breakage at the proximal end of the centriole; combined removal of the A-C linker and the inner scaffold demonstrates their joint requirement for maintaining overall centriole architecture [#0]. Beyond its structural role, the A-C linker including CCDC77 contributes to centriole duplication through regulation of the torus [#0]. Beyond these findings, no further mechanistic detail for CCDC77 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Established where CCDC77 sits in centriole ultrastructure and what it binds, addressing whether this uncharacterized coiled-coil protein has a defined structural role at the centriole.\",\n      \"evidence\": \"Ultrastructure expansion microscopy, protein depletion, and complex-formation analysis (preprint)\",\n      \"pmids\": [\n        \"bio_10.1101_2024.10.04.616628\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint version, not yet peer reviewed\",\n        \"Stoichiometry and direct binding interfaces within the WDR67/MIIP complex not resolved\",\n        \"Molecular basis of torus regulation in duplication unexplained\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Confirmed CCDC77 as an A-C linker protein between microtubule triplets that, in complex with WDR67 and MIIP, is required for triplet cohesion, centriole integrity, and duplication via the torus, establishing its function in maintaining centriole architecture.\",\n      \"evidence\": \"U-ExM, knockdown/knockout depletion with phenotyping, co-localization and complex formation analysis in cultured cells\",\n      \"pmids\": [\n        \"40707486\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which the A-C linker regulates the torus during duplication unresolved\",\n        \"No structure of the CCDC77–WDR67–MIIP complex\",\n        \"Direct versus indirect contributions of CCDC77 to cohesion not separated from other A-C linker components\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CCDC77 mechanistically couples A-C linker integrity to torus-dependent centriole duplication remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No biochemical reconstitution of the complex\",\n        \"No structural model of the A-C linker\",\n        \"Recruitment hierarchy among CCDC77, WDR67, and MIIP undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0005198\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005815\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1852241\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"CCDC77-WDR67-MIIP A-C linker complex\"\n    ],\n    \"partners\": [\n      \"WDR67\",\n      \"MIIP\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}