{"gene":"CCDC42","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2016,"finding":"Loss-of-function of Ccdc42 in male mice causes defects in the number and location of the head-tail coupling apparatus (HTCA), absence of flagellated sperm, and complete male sterility, establishing CCDC42 as necessary for sperm flagellum formation and HTCA development.","method":"Loss-of-function knockout mouse model with histological and phenotypic analysis of sperm","journal":"Developmental biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype (HTCA defects, lack of flagellated sperm, sterility), replicated across multiple observations in same study","pmids":["26945718"],"is_preprint":false},{"year":2016,"finding":"Ccdc42 expression is restricted to the brain and developing sperm (testes-enriched), establishing tissue-specific expression consistent with its role in spermiogenesis.","method":"Expression analysis in loss-of-function mouse model","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — expression pattern established in KO study, single lab but consistent with functional phenotype","pmids":["26945718"],"is_preprint":false},{"year":2019,"finding":"CCDC42 localizes to the manchette, the connecting piece (HTCA), and the sperm tail during spermatid differentiation, and also localizes to the centrosome in somatic cells.","method":"Immunofluorescence localization in mouse spermatids and somatic cells","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment in spermatids and somatic cells, single lab, multiple cell types examined","pmids":["31475146"],"is_preprint":false},{"year":2019,"finding":"CCDC42 physically interacts with ODF1 (outer dense fiber protein 1) and ODF2 in male germ cells, placing it within the protein network governing sperm-specific cytoskeletal structure formation.","method":"Co-immunoprecipitation / pulldown interaction assays in spermatids","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP interaction demonstrated, single lab, functional context supported by localization data","pmids":["31475146"],"is_preprint":false},{"year":2022,"finding":"CCDC42 interacts with CCDC38, a testis-specific protein that localizes to the manchette and sperm tail; CCDC38 and CCDC42 cooperate in sperm flagellum biogenesis.","method":"Co-immunoprecipitation in mouse testis; CCDC38 knockout mouse model","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction confirmed by Co-IP and supported by KO phenotype, single lab","pmids":["35587122"],"is_preprint":false},{"year":2023,"finding":"CCDC146 interacts with CCDC42 (as well as CCDC38) and participates in the same sperm flagellum biogenesis pathway; knockout of Ccdc146 does not affect CCDC42 protein expression levels, indicating CCDC42 is upstream or independent of CCDC146 in this network.","method":"Co-immunoprecipitation, protein interaction modeling, and Ccdc146 knockout mouse with western blot analysis","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus KO epistasis with protein-level readout, single lab, two orthogonal methods","pmids":["38038747"],"is_preprint":false},{"year":2024,"finding":"CFAP58 physically interacts with CCDC42 and may act as a cargo-stabilizing protein in the intra-manchette transport/intraflagellar transport (IMT/IFT) pathway, potentially stabilizing CCDC42 during transport.","method":"Co-immunoprecipitation and Cfap58 knockout mouse with assessment of CCDC42 localization/stability","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP interaction and functional inference from KO, single lab, pathway placement proposed with experimental support","pmids":["38602507"],"is_preprint":false}],"current_model":"CCDC42 is a coiled-coil domain-containing structural protein expressed in developing spermatids and somatic cell centrosomes that localizes to the manchette, HTCA/connecting piece, and sperm tail; it is essential for sperm flagellum biogenesis and HTCA integrity in mice, and functions within a protein complex involving ODF1, ODF2, CCDC38, CCDC146, and CFAP58 to coordinate intra-manchette transport and cytoskeletal assembly during spermiogenesis."},"narrative":{"mechanistic_narrative":"CCDC42 is a coiled-coil structural protein essential for sperm flagellum biogenesis and head-tail coupling apparatus (HTCA) integrity during spermiogenesis [PMID:26945718]. Its expression is restricted to brain and developing testes, consistent with a dedicated role in spermatid differentiation [PMID:26945718]. In spermatids CCDC42 localizes to the manchette, the connecting piece (HTCA), and the sperm tail, and it also marks the centrosome in somatic cells [PMID:31475146]. Mechanistically, CCDC42 operates within a sperm-specific cytoskeletal protein network: it physically interacts with the outer dense fiber proteins ODF1 and ODF2 [PMID:31475146], with the manchette/tail protein CCDC38 [PMID:35587122], and with CCDC146 [PMID:38038747]; loss of Ccdc146 does not alter CCDC42 protein levels, placing CCDC42 upstream of or independent from CCDC146 in this pathway [PMID:38038747]. CFAP58 also binds CCDC42 and acts to stabilize it during intra-manchette/intraflagellar transport [PMID:38602507], integrating CCDC42 into the transport machinery that builds the sperm flagellum and connecting piece.","teleology":[{"year":2016,"claim":"Established whether CCDC42 has a non-redundant function in male reproduction by testing its requirement for sperm formation in vivo.","evidence":"Loss-of-function knockout mouse with histological and phenotypic sperm analysis","pmids":["26945718"],"confidence":"High","gaps":["Did not define the molecular activity of CCDC42 at the HTCA","Did not identify interacting partners","Mechanism linking CCDC42 loss to absent flagella unresolved"]},{"year":2016,"claim":"Mapped where CCDC42 is expressed to confirm tissue specificity consistent with its spermiogenesis phenotype.","evidence":"Expression analysis in loss-of-function mouse model","pmids":["26945718"],"confidence":"Medium","gaps":["Brain expression not connected to any function","Subcellular localization not addressed at this stage"]},{"year":2019,"claim":"Determined the subcellular sites at which CCDC42 acts, linking it to the manchette, HTCA, sperm tail, and the somatic centrosome.","evidence":"Immunofluorescence localization in mouse spermatids and somatic cells","pmids":["31475146"],"confidence":"Medium","gaps":["Single-lab localization without orthogonal validation","Functional significance of centrosomal localization in somatic cells not tested"]},{"year":2019,"claim":"Identified the first direct binding partners, placing CCDC42 in the outer dense fiber/cytoskeletal protein network.","evidence":"Co-immunoprecipitation/pulldown in spermatids","pmids":["31475146"],"confidence":"Medium","gaps":["Interaction interface and stoichiometry undefined","Functional consequence of ODF1/ODF2 binding not tested by mutation"]},{"year":2022,"claim":"Extended the network to CCDC38 and showed cooperative function in flagellum biogenesis.","evidence":"Reciprocal Co-IP in mouse testis plus CCDC38 knockout","pmids":["35587122"],"confidence":"Medium","gaps":["Direct versus indirect nature of the interaction not resolved","Order of assembly within the complex unknown"]},{"year":2023,"claim":"Resolved epistatic placement by showing CCDC42 protein is unaffected by Ccdc146 loss, positioning CCDC42 upstream of or independent from CCDC146.","evidence":"Co-IP, interaction modeling, and Ccdc146 knockout with western blot","pmids":["38038747"],"confidence":"Medium","gaps":["Reciprocal test (effect of Ccdc42 loss on CCDC146) not reported here","Mechanism of co-functioning not defined"]},{"year":2024,"claim":"Implicated CCDC42 in intra-manchette/intraflagellar transport by identifying CFAP58 as a binding and stabilizing partner.","evidence":"Co-IP and Cfap58 knockout with assessment of CCDC42 localization/stability","pmids":["38602507"],"confidence":"Medium","gaps":["Cargo-stabilization role inferred from KO, not directly reconstituted","Transport mechanism and motor coupling unresolved"]},{"year":null,"claim":"The biochemical activity of CCDC42 and the architecture/assembly order of its manchette-HTCA complex remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of CCDC42 or its complex","No defined enzymatic or transport activity","Human disease relevance not established in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,6]}],"complexes":[],"partners":["ODF1","ODF2","CCDC38","CCDC146","CFAP58"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96M95","full_name":"Coiled-coil domain-containing protein 42","aliases":[],"length_aa":316,"mass_kda":38.0,"function":"Essential for male fertility. Required for sperm development","subcellular_location":"Cytoplasm, perinuclear region; Cytoplasm, cytoskeleton; Cell projection, cilium, flagellum; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q96M95/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCDC42","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/CCDC42","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":90.2}],"url":"https://www.proteinatlas.org/search/CCDC42"},"hgnc":{"alias_symbol":["FLJ32734","CCDC42A"],"prev_symbol":[]},"alphafold":{"accession":"Q96M95","domains":[{"cath_id":"1.20.5","chopping":"127-172","consensus_level":"medium","plddt":95.1846,"start":127,"end":172}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96M95","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96M95-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96M95-F1-predicted_aligned_error_v6.png","plddt_mean":87.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCDC42","jax_strain_url":"https://www.jax.org/strain/search?query=CCDC42"},"sequence":{"accession":"Q96M95","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96M95.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96M95/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96M95"}},"corpus_meta":[{"pmid":"26945718","id":"PMC_26945718","title":"Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse.","date":"2016","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/26945718","citation_count":59,"is_preprint":false},{"pmid":"31475146","id":"PMC_31475146","title":"CCDC42 Localizes to Manchette, HTCA and Tail and Interacts With ODF1 and ODF2 in the Formation of the Male Germ Cell Cytoskeleton.","date":"2019","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/31475146","citation_count":50,"is_preprint":false},{"pmid":"35587122","id":"PMC_35587122","title":"CCDC38 is required for sperm flagellum biogenesis and male fertility in mice.","date":"2022","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/35587122","citation_count":38,"is_preprint":false},{"pmid":"27936112","id":"PMC_27936112","title":"Genome-Wide Association of Heroin Dependence in Han Chinese.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27936112","citation_count":26,"is_preprint":false},{"pmid":"38038747","id":"PMC_38038747","title":"CCDC146 is required for sperm flagellum biogenesis and male fertility in mice.","date":"2023","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/38038747","citation_count":18,"is_preprint":false},{"pmid":"39744838","id":"PMC_39744838","title":"Single-Cell Transcriptomics Identifies Selective Lineage-Specific Regulation of Genes in Aortic Smooth Muscle Cells in Mice.","date":"2025","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/39744838","citation_count":11,"is_preprint":false},{"pmid":"28918577","id":"PMC_28918577","title":"Microarray-based SNP genotyping to identify genetic risk factors of triple-negative breast cancer (TNBC) in South Indian population.","date":"2017","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28918577","citation_count":10,"is_preprint":false},{"pmid":"38602507","id":"PMC_38602507","title":"CFAP58 is involved in the sperm head shaping and flagellogenesis of cattle and mice.","date":"2024","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/38602507","citation_count":8,"is_preprint":false},{"pmid":"41224710","id":"PMC_41224710","title":"Distinct Co-methylation Patterns in African and European Populations and Their Genetic Associations.","date":"2025","source":"Genomics, proteomics & bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/41224710","citation_count":1,"is_preprint":false},{"pmid":"40503472","id":"PMC_40503472","title":"Identification of Novel Genetic Loci for Parkinson's Disease Using Whole-Exome and Whole-Genome Sequencing.","date":"2025","source":"Psychiatry and clinical psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/40503472","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7293,"output_tokens":1447,"usd":0.021792,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8174,"output_tokens":2203,"usd":0.047973,"stage2_stop_reason":"end_turn"},"total_usd":0.069765,"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\": 2016,\n      \"finding\": \"Loss-of-function of Ccdc42 in male mice causes defects in the number and location of the head-tail coupling apparatus (HTCA), absence of flagellated sperm, and complete male sterility, establishing CCDC42 as necessary for sperm flagellum formation and HTCA development.\",\n      \"method\": \"Loss-of-function knockout mouse model with histological and phenotypic analysis of sperm\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype (HTCA defects, lack of flagellated sperm, sterility), replicated across multiple observations in same study\",\n      \"pmids\": [\"26945718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Ccdc42 expression is restricted to the brain and developing sperm (testes-enriched), establishing tissue-specific expression consistent with its role in spermiogenesis.\",\n      \"method\": \"Expression analysis in loss-of-function mouse model\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — expression pattern established in KO study, single lab but consistent with functional phenotype\",\n      \"pmids\": [\"26945718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CCDC42 localizes to the manchette, the connecting piece (HTCA), and the sperm tail during spermatid differentiation, and also localizes to the centrosome in somatic cells.\",\n      \"method\": \"Immunofluorescence localization in mouse spermatids and somatic cells\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment in spermatids and somatic cells, single lab, multiple cell types examined\",\n      \"pmids\": [\"31475146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CCDC42 physically interacts with ODF1 (outer dense fiber protein 1) and ODF2 in male germ cells, placing it within the protein network governing sperm-specific cytoskeletal structure formation.\",\n      \"method\": \"Co-immunoprecipitation / pulldown interaction assays in spermatids\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP interaction demonstrated, single lab, functional context supported by localization data\",\n      \"pmids\": [\"31475146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCDC42 interacts with CCDC38, a testis-specific protein that localizes to the manchette and sperm tail; CCDC38 and CCDC42 cooperate in sperm flagellum biogenesis.\",\n      \"method\": \"Co-immunoprecipitation in mouse testis; CCDC38 knockout mouse model\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction confirmed by Co-IP and supported by KO phenotype, single lab\",\n      \"pmids\": [\"35587122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CCDC146 interacts with CCDC42 (as well as CCDC38) and participates in the same sperm flagellum biogenesis pathway; knockout of Ccdc146 does not affect CCDC42 protein expression levels, indicating CCDC42 is upstream or independent of CCDC146 in this network.\",\n      \"method\": \"Co-immunoprecipitation, protein interaction modeling, and Ccdc146 knockout mouse with western blot analysis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus KO epistasis with protein-level readout, single lab, two orthogonal methods\",\n      \"pmids\": [\"38038747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CFAP58 physically interacts with CCDC42 and may act as a cargo-stabilizing protein in the intra-manchette transport/intraflagellar transport (IMT/IFT) pathway, potentially stabilizing CCDC42 during transport.\",\n      \"method\": \"Co-immunoprecipitation and Cfap58 knockout mouse with assessment of CCDC42 localization/stability\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP interaction and functional inference from KO, single lab, pathway placement proposed with experimental support\",\n      \"pmids\": [\"38602507\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CCDC42 is a coiled-coil domain-containing structural protein expressed in developing spermatids and somatic cell centrosomes that localizes to the manchette, HTCA/connecting piece, and sperm tail; it is essential for sperm flagellum biogenesis and HTCA integrity in mice, and functions within a protein complex involving ODF1, ODF2, CCDC38, CCDC146, and CFAP58 to coordinate intra-manchette transport and cytoskeletal assembly during spermiogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCDC42 is a coiled-coil structural protein essential for sperm flagellum biogenesis and head-tail coupling apparatus (HTCA) integrity during spermiogenesis [#0]. Its expression is restricted to brain and developing testes, consistent with a dedicated role in spermatid differentiation [#1]. In spermatids CCDC42 localizes to the manchette, the connecting piece (HTCA), and the sperm tail, and it also marks the centrosome in somatic cells [#2]. Mechanistically, CCDC42 operates within a sperm-specific cytoskeletal protein network: it physically interacts with the outer dense fiber proteins ODF1 and ODF2 [#3], with the manchette/tail protein CCDC38 [#4], and with CCDC146 [#5]; loss of Ccdc146 does not alter CCDC42 protein levels, placing CCDC42 upstream of or independent from CCDC146 in this pathway [#5]. CFAP58 also binds CCDC42 and acts to stabilize it during intra-manchette/intraflagellar transport [#6], integrating CCDC42 into the transport machinery that builds the sperm flagellum and connecting piece.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established whether CCDC42 has a non-redundant function in male reproduction by testing its requirement for sperm formation in vivo.\",\n      \"evidence\": \"Loss-of-function knockout mouse with histological and phenotypic sperm analysis\",\n      \"pmids\": [\"26945718\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Did not define the molecular activity of CCDC42 at the HTCA\",\n        \"Did not identify interacting partners\",\n        \"Mechanism linking CCDC42 loss to absent flagella unresolved\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Mapped where CCDC42 is expressed to confirm tissue specificity consistent with its spermiogenesis phenotype.\",\n      \"evidence\": \"Expression analysis in loss-of-function mouse model\",\n      \"pmids\": [\"26945718\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Brain expression not connected to any function\",\n        \"Subcellular localization not addressed at this stage\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Determined the subcellular sites at which CCDC42 acts, linking it to the manchette, HTCA, sperm tail, and the somatic centrosome.\",\n      \"evidence\": \"Immunofluorescence localization in mouse spermatids and somatic cells\",\n      \"pmids\": [\"31475146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab localization without orthogonal validation\",\n        \"Functional significance of centrosomal localization in somatic cells not tested\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified the first direct binding partners, placing CCDC42 in the outer dense fiber/cytoskeletal protein network.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown in spermatids\",\n      \"pmids\": [\"31475146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction interface and stoichiometry undefined\",\n        \"Functional consequence of ODF1/ODF2 binding not tested by mutation\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended the network to CCDC38 and showed cooperative function in flagellum biogenesis.\",\n      \"evidence\": \"Reciprocal Co-IP in mouse testis plus CCDC38 knockout\",\n      \"pmids\": [\"35587122\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect nature of the interaction not resolved\",\n        \"Order of assembly within the complex unknown\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Resolved epistatic placement by showing CCDC42 protein is unaffected by Ccdc146 loss, positioning CCDC42 upstream of or independent from CCDC146.\",\n      \"evidence\": \"Co-IP, interaction modeling, and Ccdc146 knockout with western blot\",\n      \"pmids\": [\"38038747\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Reciprocal test (effect of Ccdc42 loss on CCDC146) not reported here\",\n        \"Mechanism of co-functioning not defined\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Implicated CCDC42 in intra-manchette/intraflagellar transport by identifying CFAP58 as a binding and stabilizing partner.\",\n      \"evidence\": \"Co-IP and Cfap58 knockout with assessment of CCDC42 localization/stability\",\n      \"pmids\": [\"38602507\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Cargo-stabilization role inferred from KO, not directly reconstituted\",\n        \"Transport mechanism and motor coupling unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of CCDC42 and the architecture/assembly order of its manchette-HTCA complex remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of CCDC42 or its complex\",\n        \"No defined enzymatic or transport activity\",\n        \"Human disease relevance not established in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ODF1\", \"ODF2\", \"CCDC38\", \"CCDC146\", \"CFAP58\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":5,"faith_total":5,"faith_pct":100.0}}