{"gene":"CCDC73","run_date":"2026-06-09T22:57:17","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 model with phenotypic analysis (testis/body weight ratio, sperm counts, histology)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular/organismal phenotype (negative result), single lab, multiple readouts","pmids":["29563520"],"is_preprint":false},{"year":2025,"finding":"CCDC73 interacts with DNAH10, CFAP57, and DYNLL1 as part of the inner dynein arm f (IDAf) complex in cilia; loss of DNAH10 leads to reduced expression of CCDC73 (along with CFAP57 and DYNLL1), indicating CCDC73 is a component required for proper IDAf complex assembly.","method":"Co-immunoprecipitation (Co-IP), immunostaining, proteomic analysis, and Dnah10 knockout mouse model","journal":"Orphanet journal of rare diseases","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP confirming interaction, supported by KO model with expression readout, 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 interacts with DNAH10, CFAP57, and DYNLL1 and is required for proper IDAf assembly; despite its evolutionary conservation and testis-enriched expression, individual knockout of Ccdc73 in mice does not impair male fertility under laboratory conditions."},"narrative":{"mechanistic_narrative":"CCDC73 is a component of the inner dynein arm f (IDAf) complex in motile cilia, where it associates with DNAH10, CFAP57, and DYNLL1 and is required for proper IDAf complex assembly [PMID:40898283]. Loss of DNAH10 reduces CCDC73 levels alongside CFAP57 and DYNLL1, placing CCDC73 within an interdependent IDAf assembly module [PMID:40898283]. Despite this ciliary role and its conservation, individual knockout of Ccdc73 in mice is dispensable for spermatogenesis and male fertility under laboratory conditions [PMID:29563520]. Beyond these observations, no further mechanistic detail—including molecular activity or direct structural role within the dynein arm—has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"To test whether CCDC73 is required for male reproduction, its loss-of-function consequence in vivo was needed; the result established that single-gene loss is dispensable for fertility.","evidence":"CRISPR/Cas9 Ccdc73 knockout mouse with testis weight, sperm count, and histology readouts","pmids":["29563520"],"confidence":"Medium","gaps":["Does not address function in non-reproductive ciliated tissues","Possible functional redundancy with paralogs not tested","No molecular or biochemical role assigned"]},{"year":2025,"claim":"To define CCDC73's molecular context, its protein partners and assembly role were determined, establishing it as an IDAf complex component dependent on DNAH10.","evidence":"Co-IP, immunostaining, proteomics, and Dnah10 knockout mouse with expression readouts","pmids":["40898283"],"confidence":"Medium","gaps":["Direct binding partner versus indirect complex member not fully resolved","No molecular/enzymatic activity assigned to CCDC73","Ciliary motility phenotype of CCDC73 loss not measured"]},{"year":null,"claim":"The molecular function of CCDC73 within the IDAf complex and the physiological consequence of its loss in motile-cilia-dependent processes remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of CCDC73 within the dynein arm","No measurement of ciliary beat or axonemal defects upon CCDC73 loss","Mechanism of recruitment into the IDAf complex unknown"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1]}],"pathway":[],"complexes":["inner dynein arm f (IDAf) complex"],"partners":["DNAH10","CFAP57","DYNLL1"],"other_free_text":[]}},"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":42,"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":18,"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},{"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4158,"output_tokens":569,"usd":0.010504,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6898,"output_tokens":1144,"usd":0.031545,"stage2_stop_reason":"end_turn"},"total_usd":0.042049,"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\": \"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 model with phenotypic analysis (testis/body weight ratio, sperm counts, histology)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular/organismal phenotype (negative result), single lab, multiple readouts\",\n      \"pmids\": [\"29563520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CCDC73 interacts with DNAH10, CFAP57, and DYNLL1 as part of the inner dynein arm f (IDAf) complex in cilia; loss of DNAH10 leads to reduced expression of CCDC73 (along with CFAP57 and DYNLL1), indicating CCDC73 is a component required for proper IDAf complex assembly.\",\n      \"method\": \"Co-immunoprecipitation (Co-IP), immunostaining, proteomic analysis, and Dnah10 knockout mouse model\",\n      \"journal\": \"Orphanet journal of rare diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP confirming interaction, supported by KO model with expression readout, 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 interacts with DNAH10, CFAP57, and DYNLL1 and is required for proper IDAf assembly; despite its evolutionary conservation and testis-enriched expression, individual knockout of Ccdc73 in mice does not impair male fertility under laboratory conditions.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCDC73 is a component of the inner dynein arm f (IDAf) complex in motile cilia, where it associates with DNAH10, CFAP57, and DYNLL1 and is required for proper IDAf complex assembly [#1]. Loss of DNAH10 reduces CCDC73 levels alongside CFAP57 and DYNLL1, placing CCDC73 within an interdependent IDAf assembly module [#1]. Despite this ciliary role and its conservation, individual knockout of Ccdc73 in mice is dispensable for spermatogenesis and male fertility under laboratory conditions [#0]. Beyond these observations, no further mechanistic detail—including molecular activity or direct structural role within the dynein arm—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"To test whether CCDC73 is required for male reproduction, its loss-of-function consequence in vivo was needed; the result established that single-gene loss is dispensable for fertility.\",\n      \"evidence\": \"CRISPR/Cas9 Ccdc73 knockout mouse with testis weight, sperm count, and histology readouts\",\n      \"pmids\": [\"29563520\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"negative result, single lab\",\n      \"gaps\": [\n        \"Does not address function in non-reproductive ciliated tissues\",\n        \"Possible functional redundancy with paralogs not tested\",\n        \"No molecular or biochemical role assigned\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To define CCDC73's molecular context, its protein partners and assembly role were determined, establishing it as an IDAf complex component dependent on DNAH10.\",\n      \"evidence\": \"Co-IP, immunostaining, proteomics, and Dnah10 knockout mouse with expression readouts\",\n      \"pmids\": [\"40898283\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"reciprocal Co-IP plus KO expression readout, single lab\",\n      \"gaps\": [\n        \"Direct binding partner versus indirect complex member not fully resolved\",\n        \"No molecular/enzymatic activity assigned to CCDC73\",\n        \"Ciliary motility phenotype of CCDC73 loss not measured\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of CCDC73 within the IDAf complex and the physiological consequence of its loss in motile-cilia-dependent processes remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of CCDC73 within the dynein arm\",\n        \"No measurement of ciliary beat or axonemal defects upon CCDC73 loss\",\n        \"Mechanism of recruitment into the IDAf complex unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"inner dynein arm f (IDAf) complex\"],\n    \"partners\": [\"DNAH10\", \"CFAP57\", \"DYNLL1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}