{"gene":"CCDC73","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2018,"finding":"Ccdc73 knockout mice generated by CRISPR/Cas9 are fertile with no detectable difference in testis/body weight ratios, epididymal sperm counts, or testicular and epididymal histology compared to wild-type mice, indicating Ccdc73 is dispensable for spermatogenesis and male fertility in mice under laboratory conditions.","method":"CRISPR/Cas9 knockout mouse, histology, sperm count analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype, single lab","pmids":["29563520"],"is_preprint":false},{"year":2025,"finding":"CCDC73 physically interacts with DNAH10, CFAP57, and DYNLL1, contributing to the assembly of the double-headed inner dynein arm f (IDAf) complex in cilia; loss of DNAH10 leads to reduced expression of CCDC73 and improper IDAf complex assembly and ciliary dysfunction.","method":"Co-immunoprecipitation (Co-IP), immunostaining, proteomic analysis, Dnah10 knockout mouse model","journal":"Orphanet journal of rare diseases","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP confirming interaction, supported by KO mouse phenotype and proteomics, single lab","pmids":["40898283"],"is_preprint":false}],"current_model":"CCDC73 is a component of the inner dynein arm f (IDAf) complex in cilia, where it physically interacts with DNAH10, CFAP57, and DYNLL1 to support proper ciliary assembly and motility, while being dispensable for spermatogenesis and male fertility in mice under standard laboratory conditions."},"narrative":{"teleology":[{"year":2018,"claim":"Whether CCDC73 is required for spermatogenesis was unknown; CRISPR/Cas9 knockout in mice revealed that Ccdc73 is dispensable for sperm production and male fertility, narrowing the search for its essential function to other tissues or contexts.","evidence":"CRISPR/Cas9 knockout mouse with histological, sperm count, and fertility analyses","pmids":["29563520"],"confidence":"Medium","gaps":["Single-lab study; independent replication in other mouse strains not reported","Ciliary motility and respiratory phenotypes were not assessed in these knockout mice","Compensatory mechanisms by paralogous proteins were not investigated"]},{"year":2025,"claim":"The molecular context of CCDC73 was resolved by showing it physically associates with DNAH10, CFAP57, and DYNLL1 within the IDAf complex, and that DNAH10 loss destabilizes CCDC73 expression and disrupts IDAf assembly, establishing CCDC73 as a structural component of this ciliary dynein arm.","evidence":"Reciprocal co-immunoprecipitation, immunostaining, proteomics, and Dnah10 knockout mouse model","pmids":["40898283"],"confidence":"Medium","gaps":["Direct Ccdc73 knockout ciliary motility phenotype has not been characterized","No structural model of CCDC73 within the IDAf complex exists","Whether CCDC73 loss alone is sufficient to disrupt IDAf assembly remains untested"]},{"year":null,"claim":"It remains unknown whether CCDC73 loss in ciliated epithelia (e.g., airway) causes primary ciliary dyskinesia-like phenotypes, and the precise structural role of CCDC73 within the IDAf complex is unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No human genetic studies linking CCDC73 mutations to disease","No in vitro reconstitution or cryo-EM structure of CCDC73-containing IDAf complex","Tissue-specific and conditional knockout phenotypes not explored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1]}],"complexes":["IDAf (inner dynein arm f)"],"partners":["DNAH10","CFAP57","DYNLL1"],"other_free_text":[]},"mechanistic_narrative":"CCDC73 is a component of the double-headed inner dynein arm f (IDAf) complex in cilia, where it physically interacts with DNAH10, CFAP57, and DYNLL1 to support proper IDAf assembly and ciliary motility; loss of DNAH10 leads to reduced CCDC73 expression and defective IDAf complex formation [PMID:40898283]. Ccdc73 knockout mice show no detectable defects in spermatogenesis or male fertility under laboratory conditions, indicating that CCDC73 is dispensable for these processes [PMID:29563520]."},"prefetch_data":{"uniprot":{"accession":"Q6ZRK6","full_name":"Coiled-coil domain-containing protein 73","aliases":["Sarcoma antigen NY-SAR-79"],"length_aa":1079,"mass_kda":124.2,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q6ZRK6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCDC73","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CCDC73","total_profiled":1310},"omim":[{"mim_id":"619676","title":"SPERM MICROTUBULE INNER PROTEIN 9; SPMIP9","url":"https://www.omim.org/entry/619676"},{"mim_id":"612328","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 73: CCDC73","url":"https://www.omim.org/entry/612328"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"testis","ntpm":3.5}],"url":"https://www.proteinatlas.org/search/CCDC73"},"hgnc":{"alias_symbol":["NY-SAR-79"],"prev_symbol":[]},"alphafold":{"accession":"Q6ZRK6","domains":[{"cath_id":"1.20.5","chopping":"274-317","consensus_level":"medium","plddt":87.6007,"start":274,"end":317},{"cath_id":"1.20.5","chopping":"330-376","consensus_level":"medium","plddt":76.9085,"start":330,"end":376}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRK6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRK6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRK6-F1-predicted_aligned_error_v6.png","plddt_mean":53.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCDC73","jax_strain_url":"https://www.jax.org/strain/search?query=CCDC73"},"sequence":{"accession":"Q6ZRK6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZRK6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZRK6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRK6"}},"corpus_meta":[{"pmid":"29563520","id":"PMC_29563520","title":"The evolutionarily conserved genes: Tex37, Ccdc73, Prss55 and Nxt2 are dispensable for fertility in mice.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29563520","citation_count":41,"is_preprint":false},{"pmid":"24912414","id":"PMC_24912414","title":"A novel Alu-mediated microdeletion at 11p13 removes WT1 in a patient with cryptorchidism and azoospermia.","date":"2014","source":"Reproductive biomedicine online","url":"https://pubmed.ncbi.nlm.nih.gov/24912414","citation_count":17,"is_preprint":false},{"pmid":"40898283","id":"PMC_40898283","title":"DNAH10 mutation cause primary ciliary dyskinesia with defects of IDAf complex assembly and lung fibrosis manifestation.","date":"2025","source":"Orphanet journal of rare diseases","url":"https://pubmed.ncbi.nlm.nih.gov/40898283","citation_count":0,"is_preprint":false},{"pmid":"41645336","id":"PMC_41645336","title":"Genomic analysis reveals convergent signatures of selection for milk traits in sheep and goats.","date":"2026","source":"Journal of animal science and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/41645336","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3398,"output_tokens":518,"usd":0.008982},"stage2":{"model":"claude-opus-4-6","input_tokens":3681,"output_tokens":935,"usd":0.06267},"total_usd":0.071652,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Ccdc73 knockout mice generated by CRISPR/Cas9 are fertile with no detectable difference in testis/body weight ratios, epididymal sperm counts, or testicular and epididymal histology compared to wild-type mice, indicating Ccdc73 is dispensable for spermatogenesis and male fertility in mice under laboratory conditions.\",\n      \"method\": \"CRISPR/Cas9 knockout mouse, histology, sperm count analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype, single lab\",\n      \"pmids\": [\"29563520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CCDC73 physically interacts with DNAH10, CFAP57, and DYNLL1, contributing to the assembly of the double-headed inner dynein arm f (IDAf) complex in cilia; loss of DNAH10 leads to reduced expression of CCDC73 and improper IDAf complex assembly and ciliary dysfunction.\",\n      \"method\": \"Co-immunoprecipitation (Co-IP), immunostaining, proteomic analysis, Dnah10 knockout mouse model\",\n      \"journal\": \"Orphanet journal of rare diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP confirming interaction, supported by KO mouse phenotype and proteomics, single lab\",\n      \"pmids\": [\"40898283\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CCDC73 is a component of the inner dynein arm f (IDAf) complex in cilia, where it physically interacts with DNAH10, CFAP57, and DYNLL1 to support proper ciliary assembly and motility, while being dispensable for spermatogenesis and male fertility in mice under standard laboratory conditions.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CCDC73 is a component of the double-headed inner dynein arm f (IDAf) complex in cilia, where it physically interacts with DNAH10, CFAP57, and DYNLL1 to support proper IDAf assembly and ciliary motility; loss of DNAH10 leads to reduced CCDC73 expression and defective IDAf complex formation [PMID:40898283]. Ccdc73 knockout mice show no detectable defects in spermatogenesis or male fertility under laboratory conditions, indicating that CCDC73 is dispensable for these processes [PMID:29563520].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether CCDC73 is required for spermatogenesis was unknown; CRISPR/Cas9 knockout in mice revealed that Ccdc73 is dispensable for sperm production and male fertility, narrowing the search for its essential function to other tissues or contexts.\",\n      \"evidence\": \"CRISPR/Cas9 knockout mouse with histological, sperm count, and fertility analyses\",\n      \"pmids\": [\"29563520\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; independent replication in other mouse strains not reported\",\n        \"Ciliary motility and respiratory phenotypes were not assessed in these knockout mice\",\n        \"Compensatory mechanisms by paralogous proteins were not investigated\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The molecular context of CCDC73 was resolved by showing it physically associates with DNAH10, CFAP57, and DYNLL1 within the IDAf complex, and that DNAH10 loss destabilizes CCDC73 expression and disrupts IDAf assembly, establishing CCDC73 as a structural component of this ciliary dynein arm.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, immunostaining, proteomics, and Dnah10 knockout mouse model\",\n      \"pmids\": [\"40898283\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct Ccdc73 knockout ciliary motility phenotype has not been characterized\",\n        \"No structural model of CCDC73 within the IDAf complex exists\",\n        \"Whether CCDC73 loss alone is sufficient to disrupt IDAf assembly remains untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether CCDC73 loss in ciliated epithelia (e.g., airway) causes primary ciliary dyskinesia-like phenotypes, and the precise structural role of CCDC73 within the IDAf complex is unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human genetic studies linking CCDC73 mutations to disease\",\n        \"No in vitro reconstitution or cryo-EM structure of CCDC73-containing IDAf complex\",\n        \"Tissue-specific and conditional knockout phenotypes not explored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"IDAf (inner dynein arm f)\"],\n    \"partners\": [\"DNAH10\", \"CFAP57\", \"DYNLL1\"],\n    \"other_free_text\": []\n  }\n}\n```"}