{"gene":"CCDC42","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2016,"finding":"Loss-of-function mutation in Ccdc42 in male mice causes defects in the number and location of the head-tail coupling apparatus (HTCA) and absence of flagellated sperm, establishing CCDC42 as necessary for HTCA formation and sperm flagella development. Ccdc42 expression is restricted to the brain and developing sperm.","method":"Knockout mouse model (loss-of-function allele), histological and morphological analysis of testes and sperm","journal":"Developmental biology","confidence":"High","confidence_rationale":"Tier 2 — clean KO mouse with defined cellular phenotypes (HTCA malformation, absence of flagellated sperm, male sterility)","pmids":["26945718"],"is_preprint":false},{"year":2019,"finding":"CCDC42 localizes to the manchette, connecting piece (HTCA), and sperm tail during spermiogenesis, and also localizes to the centrosome in somatic cells. CCDC42 physically interacts with ODF1 (outer dense fiber protein 1) and ODF2, implicating it in the protein network forming spermatid-specific cytoskeletal structures.","method":"Immunofluorescence localization in spermatids and somatic cells; co-immunoprecipitation/pulldown with ODF1 and ODF2","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 3 — subcellular localization plus single Co-IP/pulldown interactions with ODF1 and ODF2 in one study","pmids":["31475146"],"is_preprint":false},{"year":2022,"finding":"CCDC42 physically interacts with CCDC38, and CCDC38 localizes to the manchette and sperm tail. Loss of CCDC38 causes manchette distortion and MMAF (multiple morphological abnormalities of the flagella), and reduces ODF2 transport to the flagellum; CCDC38 also interacts with IFT88 and ODF2, placing CCDC42 in an intraflagellar/intra-manchette transport complex.","method":"Co-immunoprecipitation (CCDC42–CCDC38 interaction), Ccdc38 knockout mice, immunofluorescence, western blot","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 3 — reciprocal interaction demonstrated by Co-IP in a single study; functional context supported by KO phenotype","pmids":["35587122"],"is_preprint":false},{"year":2023,"finding":"CCDC42 physically interacts with CCDC146, which also interacts with CCDC38 and IFT complexes (IFT88, IFT20). Knockout of Ccdc146 does not affect CCDC42 or CCDC38 expression, but leads to flagellum and manchette defects, suggesting CCDC42 functions within a CCDC38–CCDC146–IFT network for sperm flagellum biogenesis. Atomic-level interaction models between CCDC146 and CCDC42 were built and validated.","method":"Co-immunoprecipitation, Ccdc146 knockout mice, computational interaction modeling with experimental validation, western blot","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP plus structural modeling and KO phenotype in a single study; interaction validated by multiple methods","pmids":["38038747"],"is_preprint":false},{"year":2024,"finding":"CFAP58 interacts with CCDC42 and may act as a stabilizing protein for CCDC42 in the intra-manchette transport/intraflagellar transport (IMT/IFT) pathway. Loss of Cfap58 causes reduction in CCDC42 protein levels at the manchette.","method":"Co-immunoprecipitation (CFAP58–CCDC42), Cfap58 knockout mice, immunofluorescence, western blot","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 3 — single Co-IP plus KO functional consequence on CCDC42 levels; single laboratory","pmids":["38602507"],"is_preprint":false}],"current_model":"CCDC42 is a coiled-coil domain-containing structural protein that localizes to the manchette, head-tail coupling apparatus (HTCA), and sperm tail during spermiogenesis (and to the centrosome in somatic cells), where it interacts with ODF1, ODF2, CCDC38, CCDC146, and CFAP58 as part of an intra-manchette/intraflagellar transport complex required for sperm head shaping and flagellum biogenesis; loss of CCDC42 in mice disrupts HTCA formation and abolishes flagellated sperm, causing male sterility."},"narrative":{"teleology":[{"year":2016,"claim":"The first loss-of-function study established that CCDC42 is required for head-tail coupling apparatus formation and sperm flagellum development, resolving the question of whether this uncharacterized coiled-coil protein has an essential developmental role.","evidence":"Ccdc42 knockout mouse with histological/morphological analysis of testes and sperm showing absent flagella and HTCA defects","pmids":["26945718"],"confidence":"High","gaps":["Subcellular localization of CCDC42 during spermiogenesis was not defined","No interacting partners identified","Mechanism by which CCDC42 loss disrupts HTCA was unknown"]},{"year":2019,"claim":"Subcellular mapping placed CCDC42 at the manchette, HTCA, sperm tail, and somatic centrosome, and identified ODF1 and ODF2 as direct physical partners, situating CCDC42 within the cytoskeletal scaffold of spermatid-specific structures.","evidence":"Immunofluorescence in spermatids and somatic cells; co-immunoprecipitation/pulldown with ODF1 and ODF2","pmids":["31475146"],"confidence":"Medium","gaps":["ODF1 and ODF2 interactions shown by single Co-IP/pulldown without independent reciprocal validation in a second laboratory","Functional consequence of CCDC42–ODF interactions not tested","Whether CCDC42 acts in transport versus as a structural anchor was unresolved"]},{"year":2022,"claim":"Identification of CCDC38 as a CCDC42 interactor, combined with the CCDC38 knockout phenotype (manchette distortion, MMAF, reduced ODF2 transport), placed CCDC42 within an intra-manchette/intraflagellar transport complex required for cargo delivery to the flagellum.","evidence":"Co-immunoprecipitation of CCDC42–CCDC38; Ccdc38 knockout mice with immunofluorescence and western blot","pmids":["35587122"],"confidence":"Medium","gaps":["Direct transport function of CCDC42 itself (versus scaffolding) not distinguished","Stoichiometry and order of assembly of the CCDC42–CCDC38–IFT complex unknown","Whether CCDC42 loss phenocopies CCDC38 loss at the molecular cargo level was untested"]},{"year":2023,"claim":"CCDC146 was added to the CCDC42-containing network, and structural modeling of the CCDC146–CCDC42 interface together with the Ccdc146 knockout phenotype refined the picture of a modular CCDC38–CCDC42–CCDC146–IFT complex for flagellum biogenesis.","evidence":"Co-immunoprecipitation, computational interaction modeling with experimental validation, Ccdc146 knockout mice","pmids":["38038747"],"confidence":"Medium","gaps":["No high-resolution experimental structure of the complex exists","Whether CCDC42 directly contacts IFT particles or only through CCDC38/CCDC146 is unresolved","Functional redundancy among coiled-coil subunits not tested"]},{"year":2024,"claim":"CFAP58 was identified as another CCDC42 interactor that stabilizes CCDC42 protein levels at the manchette, indicating upstream regulation of CCDC42 within the IMT/IFT pathway.","evidence":"Co-immunoprecipitation of CFAP58–CCDC42; Cfap58 knockout mice showing reduced manchette CCDC42 levels","pmids":["38602507"],"confidence":"Medium","gaps":["Single Co-IP in one laboratory; independent confirmation pending","Mechanism of CFAP58-mediated stabilization (e.g., protecting from degradation vs. promoting localization) is unknown","Whether CFAP58 loss fully recapitulates CCDC42 loss phenotype not shown"]},{"year":null,"claim":"Key open questions include the precise cargo-binding mechanism of CCDC42, the atomic structure of the full manchette transport complex, whether CCDC42's centrosomal localization in somatic cells reflects a non-reproductive function, and whether human CCDC42 mutations cause male infertility.","evidence":"","pmids":[],"confidence":"Low","gaps":["No human genetic data linking CCDC42 variants to infertility","No reconstituted biochemistry of the CCDC42-containing transport complex","Somatic (centrosomal) function of CCDC42 entirely unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,2,3]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0,1,2,3,4]}],"complexes":[],"partners":["ODF1","ODF2","CCDC38","CCDC146","CFAP58"],"other_free_text":[]},"mechanistic_narrative":"CCDC42 is a coiled-coil domain-containing protein that localizes to the manchette, head-tail coupling apparatus (HTCA), and sperm tail during spermiogenesis, and to the centrosome in somatic cells [PMID:31475146]. It physically interacts with ODF1, ODF2, CCDC38, CCDC146, and CFAP58, forming part of an intra-manchette/intraflagellar transport complex that delivers structural cargoes such as ODF2 to the assembling flagellum [PMID:31475146, PMID:35587122, PMID:38038747, PMID:38602507]. Loss of CCDC42 in mice disrupts HTCA formation, abolishes flagellated sperm production, and causes male sterility, establishing it as essential for sperm head shaping and flagellum biogenesis [PMID:26945718]."},"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":49,"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":33,"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":"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":"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":9,"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":5,"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":6528,"output_tokens":1370,"usd":0.020067},"stage2":{"model":"claude-opus-4-6","input_tokens":4601,"output_tokens":1788,"usd":0.101557},"total_usd":0.121624,"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\": 2016,\n      \"finding\": \"Loss-of-function mutation in Ccdc42 in male mice causes defects in the number and location of the head-tail coupling apparatus (HTCA) and absence of flagellated sperm, establishing CCDC42 as necessary for HTCA formation and sperm flagella development. Ccdc42 expression is restricted to the brain and developing sperm.\",\n      \"method\": \"Knockout mouse model (loss-of-function allele), histological and morphological analysis of testes and sperm\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO mouse with defined cellular phenotypes (HTCA malformation, absence of flagellated sperm, male sterility)\",\n      \"pmids\": [\"26945718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CCDC42 localizes to the manchette, connecting piece (HTCA), and sperm tail during spermiogenesis, and also localizes to the centrosome in somatic cells. CCDC42 physically interacts with ODF1 (outer dense fiber protein 1) and ODF2, implicating it in the protein network forming spermatid-specific cytoskeletal structures.\",\n      \"method\": \"Immunofluorescence localization in spermatids and somatic cells; co-immunoprecipitation/pulldown with ODF1 and ODF2\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — subcellular localization plus single Co-IP/pulldown interactions with ODF1 and ODF2 in one study\",\n      \"pmids\": [\"31475146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCDC42 physically interacts with CCDC38, and CCDC38 localizes to the manchette and sperm tail. Loss of CCDC38 causes manchette distortion and MMAF (multiple morphological abnormalities of the flagella), and reduces ODF2 transport to the flagellum; CCDC38 also interacts with IFT88 and ODF2, placing CCDC42 in an intraflagellar/intra-manchette transport complex.\",\n      \"method\": \"Co-immunoprecipitation (CCDC42–CCDC38 interaction), Ccdc38 knockout mice, immunofluorescence, western blot\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — reciprocal interaction demonstrated by Co-IP in a single study; functional context supported by KO phenotype\",\n      \"pmids\": [\"35587122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CCDC42 physically interacts with CCDC146, which also interacts with CCDC38 and IFT complexes (IFT88, IFT20). Knockout of Ccdc146 does not affect CCDC42 or CCDC38 expression, but leads to flagellum and manchette defects, suggesting CCDC42 functions within a CCDC38–CCDC146–IFT network for sperm flagellum biogenesis. Atomic-level interaction models between CCDC146 and CCDC42 were built and validated.\",\n      \"method\": \"Co-immunoprecipitation, Ccdc146 knockout mice, computational interaction modeling with experimental validation, western blot\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP plus structural modeling and KO phenotype in a single study; interaction validated by multiple methods\",\n      \"pmids\": [\"38038747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CFAP58 interacts with CCDC42 and may act as a stabilizing protein for CCDC42 in the intra-manchette transport/intraflagellar transport (IMT/IFT) pathway. Loss of Cfap58 causes reduction in CCDC42 protein levels at the manchette.\",\n      \"method\": \"Co-immunoprecipitation (CFAP58–CCDC42), Cfap58 knockout mice, immunofluorescence, western blot\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP plus KO functional consequence on CCDC42 levels; single laboratory\",\n      \"pmids\": [\"38602507\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CCDC42 is a coiled-coil domain-containing structural protein that localizes to the manchette, head-tail coupling apparatus (HTCA), and sperm tail during spermiogenesis (and to the centrosome in somatic cells), where it interacts with ODF1, ODF2, CCDC38, CCDC146, and CFAP58 as part of an intra-manchette/intraflagellar transport complex required for sperm head shaping and flagellum biogenesis; loss of CCDC42 in mice disrupts HTCA formation and abolishes flagellated sperm, causing male sterility.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CCDC42 is a coiled-coil domain-containing protein that localizes to the manchette, head-tail coupling apparatus (HTCA), and sperm tail during spermiogenesis, and to the centrosome in somatic cells [PMID:31475146]. It physically interacts with ODF1, ODF2, CCDC38, CCDC146, and CFAP58, forming part of an intra-manchette/intraflagellar transport complex that delivers structural cargoes such as ODF2 to the assembling flagellum [PMID:31475146, PMID:35587122, PMID:38038747, PMID:38602507]. Loss of CCDC42 in mice disrupts HTCA formation, abolishes flagellated sperm production, and causes male sterility, establishing it as essential for sperm head shaping and flagellum biogenesis [PMID:26945718].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"The first loss-of-function study established that CCDC42 is required for head-tail coupling apparatus formation and sperm flagellum development, resolving the question of whether this uncharacterized coiled-coil protein has an essential developmental role.\",\n      \"evidence\": \"Ccdc42 knockout mouse with histological/morphological analysis of testes and sperm showing absent flagella and HTCA defects\",\n      \"pmids\": [\"26945718\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Subcellular localization of CCDC42 during spermiogenesis was not defined\",\n        \"No interacting partners identified\",\n        \"Mechanism by which CCDC42 loss disrupts HTCA was unknown\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Subcellular mapping placed CCDC42 at the manchette, HTCA, sperm tail, and somatic centrosome, and identified ODF1 and ODF2 as direct physical partners, situating CCDC42 within the cytoskeletal scaffold of spermatid-specific structures.\",\n      \"evidence\": \"Immunofluorescence in spermatids and somatic cells; co-immunoprecipitation/pulldown with ODF1 and ODF2\",\n      \"pmids\": [\"31475146\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ODF1 and ODF2 interactions shown by single Co-IP/pulldown without independent reciprocal validation in a second laboratory\",\n        \"Functional consequence of CCDC42–ODF interactions not tested\",\n        \"Whether CCDC42 acts in transport versus as a structural anchor was unresolved\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identification of CCDC38 as a CCDC42 interactor, combined with the CCDC38 knockout phenotype (manchette distortion, MMAF, reduced ODF2 transport), placed CCDC42 within an intra-manchette/intraflagellar transport complex required for cargo delivery to the flagellum.\",\n      \"evidence\": \"Co-immunoprecipitation of CCDC42–CCDC38; Ccdc38 knockout mice with immunofluorescence and western blot\",\n      \"pmids\": [\"35587122\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct transport function of CCDC42 itself (versus scaffolding) not distinguished\",\n        \"Stoichiometry and order of assembly of the CCDC42–CCDC38–IFT complex unknown\",\n        \"Whether CCDC42 loss phenocopies CCDC38 loss at the molecular cargo level was untested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"CCDC146 was added to the CCDC42-containing network, and structural modeling of the CCDC146–CCDC42 interface together with the Ccdc146 knockout phenotype refined the picture of a modular CCDC38–CCDC42–CCDC146–IFT complex for flagellum biogenesis.\",\n      \"evidence\": \"Co-immunoprecipitation, computational interaction modeling with experimental validation, Ccdc146 knockout mice\",\n      \"pmids\": [\"38038747\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No high-resolution experimental structure of the complex exists\",\n        \"Whether CCDC42 directly contacts IFT particles or only through CCDC38/CCDC146 is unresolved\",\n        \"Functional redundancy among coiled-coil subunits not tested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"CFAP58 was identified as another CCDC42 interactor that stabilizes CCDC42 protein levels at the manchette, indicating upstream regulation of CCDC42 within the IMT/IFT pathway.\",\n      \"evidence\": \"Co-immunoprecipitation of CFAP58–CCDC42; Cfap58 knockout mice showing reduced manchette CCDC42 levels\",\n      \"pmids\": [\"38602507\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP in one laboratory; independent confirmation pending\",\n        \"Mechanism of CFAP58-mediated stabilization (e.g., protecting from degradation vs. promoting localization) is unknown\",\n        \"Whether CFAP58 loss fully recapitulates CCDC42 loss phenotype not shown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the precise cargo-binding mechanism of CCDC42, the atomic structure of the full manchette transport complex, whether CCDC42's centrosomal localization in somatic cells reflects a non-reproductive function, and whether human CCDC42 mutations cause male infertility.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human genetic data linking CCDC42 variants to infertility\",\n        \"No reconstituted biochemistry of the CCDC42-containing transport complex\",\n        \"Somatic (centrosomal) function of CCDC42 entirely unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0, 1, 2, 3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ODF1\", \"ODF2\", \"CCDC38\", \"CCDC146\", \"CFAP58\"],\n    \"other_free_text\": []\n  }\n}\n```"}