{"gene":"CCDC38","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2014,"finding":"CCDC38 localizes to the centrosome in cultured mammalian cells, identified as a centrosome-associated protein by mass spectrometry of sperm centrioles followed by localization assessment.","method":"Mass spectrometry of sperm centrioles + localization assessment in cultured cells","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization experiment with MS discovery, single study","pmids":["25074808"],"is_preprint":false},{"year":2016,"finding":"CCDC38 interacts with ubiquitinated histone H2A in mouse testes, as demonstrated by immunofluorescence co-localization and co-immunoprecipitation assays.","method":"Co-immunoprecipitation and immunofluorescence in mouse testes","journal":"Molecular medicine reports","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP/immunofluorescence, single study, limited functional follow-up","pmids":["27278724"],"is_preprint":false},{"year":2022,"finding":"CCDC38 interacts with CCDC42 and localizes on the manchette and sperm tail during spermiogenesis; knockout of Ccdc38 in male mice causes distorted manchette, multiple morphological abnormalities of the flagella (MMAF), and male sterility.","method":"Co-immunoprecipitation, immunofluorescence, and Ccdc38 knockout mouse model with phenotypic analysis","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus clean KO with defined cellular and organismal phenotype","pmids":["35587122"],"is_preprint":false},{"year":2022,"finding":"CCDC38 interacts with intraflagellar transport protein IFT88 and outer dense fiber protein ODF2; knockout of Ccdc38 reduces transport/delivery of ODF2 to the sperm flagellum, implicating CCDC38 in IFT-mediated flagellar cargo transport.","method":"Co-immunoprecipitation and protein level analysis in Ccdc38 knockout mice","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 — Co-IP combined with KO model showing reduced ODF2 transport, single rigorous study","pmids":["35587122"],"is_preprint":false},{"year":2023,"finding":"CCDC146 interacts with CCDC38 (validated by Co-IP and atomic-level interaction modeling); the CCDC38–CCDC42–CCDC146 complex cooperates in IFT-mediated flagellum biogenesis, with CCDC146 knockout reducing IFT88 and IFT20 but not CCDC38 levels.","method":"Co-immunoprecipitation, structural interaction modeling, and Ccdc146 knockout mouse analysis","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP with structural modeling, single study focused on CCDC146 but directly implicates CCDC38 complex","pmids":["38038747"],"is_preprint":false},{"year":2023,"finding":"CCDC38 is required for acrosome biogenesis and fibrous sheath assembly in mice; Ccdc38 knockout causes acrosomal hypoplasia with loosely anchored acrosomal membrane, disorganized fibrous sheaths, and decreased/aberrant distribution of TEKT3 (a protein associated with acrosome biogenesis) in testes and sperm.","method":"Base-editing-induced Ccdc38 knockout mouse model with ultrastructural and immunofluorescence analysis; ICSI rescue experiment","journal":"Journal of genetics and genomics","confidence":"High","confidence_rationale":"Tier 2 — clean KO with multiple orthogonal phenotypic readouts and molecular marker analysis, functional rescue by ICSI","pmids":["37709195"],"is_preprint":false}],"current_model":"CCDC38 is a testis-enriched, centrosome- and manchette-associated protein that forms complexes with CCDC42, CCDC146, and IFT88 to facilitate intraflagellar transport of structural cargo (including ODF2) to the growing sperm flagellum, and additionally interacts with TEKT3 and ubiquitinated histone H2A to support acrosome biogenesis and fibrous sheath assembly during spermiogenesis; its loss causes distorted manchette, multiple morphological abnormalities of the flagella (MMAF), acrosomal hypoplasia, and complete male infertility in mice."},"narrative":{"teleology":[{"year":2014,"claim":"Identification of CCDC38 as a centrosome-associated protein established its connection to the microtubule-organizing center, providing the first subcellular context for its function.","evidence":"Mass spectrometry of bovine sperm centrioles followed by localization assessment in cultured mammalian cells","pmids":["25074808"],"confidence":"Medium","gaps":["No functional assay performed; centrosomal role inferred solely from localization","Relevance to spermatogenesis versus general centrosome biology was unclear"]},{"year":2016,"claim":"Discovery of an interaction between CCDC38 and ubiquitinated histone H2A in mouse testes raised the possibility that CCDC38 participates in chromatin-related processes during spermiogenesis, though the functional significance was not resolved.","evidence":"Co-immunoprecipitation and immunofluorescence co-localization in mouse testes","pmids":["27278724"],"confidence":"Low","gaps":["Single Co-IP without reciprocal validation or functional follow-up","Biological consequence of the H2A interaction remains unknown","No loss-of-function experiment to test requirement"]},{"year":2022,"claim":"Knockout studies and interaction mapping established CCDC38 as a manchette- and flagellum-localized protein that complexes with CCDC42 and the IFT component IFT88 to transport ODF2 to the sperm tail, with its loss causing MMAF and male sterility — answering the central question of its physiological function.","evidence":"Reciprocal Co-IP identifying CCDC42, IFT88, and ODF2 interactions; Ccdc38 knockout mouse showing distorted manchette, MMAF, reduced ODF2 delivery, and complete infertility","pmids":["35587122"],"confidence":"High","gaps":["Direct biochemical reconstitution of the CCDC38–IFT88 transport complex has not been performed","Whether CCDC38 is a cargo adaptor versus a structural scaffold for IFT remains unresolved","Human genetic validation (MMAF patient mutations in CCDC38) not yet reported"]},{"year":2023,"claim":"Demonstration that CCDC146 is a third core member of the CCDC38–CCDC42 complex and that CCDC146 loss reduces IFT88/IFT20 levels without affecting CCDC38 refined the hierarchical assembly of this flagellum-biogenesis module.","evidence":"Co-IP and atomic-level interaction modeling of CCDC146–CCDC38; Ccdc146 knockout mouse with IFT protein quantification","pmids":["38038747"],"confidence":"Medium","gaps":["Stoichiometry and assembly order of the trimeric complex are unknown","Whether CCDC38 recruits CCDC146 or vice versa has not been tested by sequential depletion"]},{"year":2023,"claim":"An independent knockout confirmed the flagellar phenotype and extended CCDC38's role to acrosome biogenesis and fibrous sheath assembly, showing acrosomal hypoplasia and aberrant TEKT3 distribution, thereby broadening the functional scope beyond IFT-mediated tail formation.","evidence":"Base-editing Ccdc38 knockout mouse with TEM ultrastructure, immunofluorescence for TEKT3, and ICSI fertility rescue","pmids":["37709195"],"confidence":"High","gaps":["Mechanism linking CCDC38 to acrosomal membrane anchoring is undefined","Whether TEKT3 is a direct physical partner or a downstream marker has not been distinguished","Relationship between the IFT-transport function and acrosome biogenesis function is unclear"]},{"year":null,"claim":"Key unresolved questions include whether CCDC38 mutations cause human male infertility, how CCDC38 coordinates its dual roles in flagellar IFT and acrosome biogenesis, and the structural basis of the CCDC38–CCDC42–CCDC146 complex.","evidence":"","pmids":[],"confidence":"Low","gaps":["No human genetic studies linking CCDC38 variants to MMAF or infertility","No structural or cryo-EM data for the trimeric complex","Mechanism coupling manchette-based transport to acrosomal vesicle formation is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2,3,4]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[2,5]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2,3]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[2,3,4,5]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[2,5]}],"complexes":["CCDC38–CCDC42–CCDC146 complex"],"partners":["CCDC42","CCDC146","IFT88","ODF2","TEKT3"],"other_free_text":[]},"mechanistic_narrative":"CCDC38 is a centrosome- and manchette-associated coiled-coil protein essential for sperm flagellum biogenesis, acrosome formation, and male fertility. During spermiogenesis, CCDC38 forms a complex with CCDC42 and CCDC146 on the manchette and sperm tail, where it interacts with the intraflagellar transport protein IFT88 to facilitate delivery of structural cargo such as ODF2 to the growing flagellum; loss of CCDC38 in mice causes distorted manchette morphology, multiple morphological abnormalities of the flagella (MMAF), acrosomal hypoplasia with disorganized fibrous sheaths, and complete male sterility [PMID:35587122, PMID:38038747, PMID:37709195]. CCDC38 additionally localizes to centrosomes in mammalian cells and interacts with ubiquitinated histone H2A and the structural protein TEKT3 in the testis, linking it to both cytoskeletal organization and chromatin-associated processes during sperm development [PMID:25074808, PMID:27278724, PMID:37709195]."},"prefetch_data":{"uniprot":{"accession":"Q502W7","full_name":"Coiled-coil domain-containing protein 38","aliases":[],"length_aa":563,"mass_kda":65.3,"function":"Essential for male fertility. Required for sperm flagellum biogenesis. Also required for acrosome biogenesis. Required for the attachment of developing acrosomes to the nucleus during spermiogenesis and may be involved in the transport of fibrous sheath components","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, perinuclear region; Cell projection, cilium, flagellum; Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q502W7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CCDC38","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CCDC38","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":15.7}],"url":"https://www.proteinatlas.org/search/CCDC38"},"hgnc":{"alias_symbol":["FLJ40089"],"prev_symbol":[]},"alphafold":{"accession":"Q502W7","domains":[{"cath_id":"1.20.5","chopping":"337-418","consensus_level":"medium","plddt":93.9362,"start":337,"end":418},{"cath_id":"4.10.290","chopping":"449-519","consensus_level":"medium","plddt":86.2776,"start":449,"end":519}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q502W7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q502W7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q502W7-F1-predicted_aligned_error_v6.png","plddt_mean":73.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CCDC38","jax_strain_url":"https://www.jax.org/strain/search?query=CCDC38"},"sequence":{"accession":"Q502W7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q502W7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q502W7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q502W7"}},"corpus_meta":[{"pmid":"25074808","id":"PMC_25074808","title":"Proteomic analysis of mammalian sperm cells identifies new components of the centrosome.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/25074808","citation_count":93,"is_preprint":false},{"pmid":"31255637","id":"PMC_31255637","title":"Proteomics and single-cell RNA analysis of Akap4-knockout mice model confirm indispensable role of Akap4 in spermatogenesis.","date":"2019","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/31255637","citation_count":59,"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":"24786987","id":"PMC_24786987","title":"Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction.","date":"2014","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24786987","citation_count":30,"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":"27278724","id":"PMC_27278724","title":"Identification and characteristics of the testes-specific gene, Ccdc38, in mice.","date":"2016","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/27278724","citation_count":7,"is_preprint":false},{"pmid":"37709195","id":"PMC_37709195","title":"Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice.","date":"2023","source":"Journal of genetics and genomics = Yi chuan xue bao","url":"https://pubmed.ncbi.nlm.nih.gov/37709195","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4538,"output_tokens":1347,"usd":0.01691},"stage2":{"model":"claude-opus-4-6","input_tokens":4588,"output_tokens":1885,"usd":0.105097},"total_usd":0.122007,"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\": 2014,\n      \"finding\": \"CCDC38 localizes to the centrosome in cultured mammalian cells, identified as a centrosome-associated protein by mass spectrometry of sperm centrioles followed by localization assessment.\",\n      \"method\": \"Mass spectrometry of sperm centrioles + localization assessment in cultured cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiment with MS discovery, single study\",\n      \"pmids\": [\"25074808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CCDC38 interacts with ubiquitinated histone H2A in mouse testes, as demonstrated by immunofluorescence co-localization and co-immunoprecipitation assays.\",\n      \"method\": \"Co-immunoprecipitation and immunofluorescence in mouse testes\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP/immunofluorescence, single study, limited functional follow-up\",\n      \"pmids\": [\"27278724\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCDC38 interacts with CCDC42 and localizes on the manchette and sperm tail during spermiogenesis; knockout of Ccdc38 in male mice causes distorted manchette, multiple morphological abnormalities of the flagella (MMAF), and male sterility.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, and Ccdc38 knockout mouse model with phenotypic analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus clean KO with defined cellular and organismal phenotype\",\n      \"pmids\": [\"35587122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCDC38 interacts with intraflagellar transport protein IFT88 and outer dense fiber protein ODF2; knockout of Ccdc38 reduces transport/delivery of ODF2 to the sperm flagellum, implicating CCDC38 in IFT-mediated flagellar cargo transport.\",\n      \"method\": \"Co-immunoprecipitation and protein level analysis in Ccdc38 knockout mice\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP combined with KO model showing reduced ODF2 transport, single rigorous study\",\n      \"pmids\": [\"35587122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CCDC146 interacts with CCDC38 (validated by Co-IP and atomic-level interaction modeling); the CCDC38–CCDC42–CCDC146 complex cooperates in IFT-mediated flagellum biogenesis, with CCDC146 knockout reducing IFT88 and IFT20 but not CCDC38 levels.\",\n      \"method\": \"Co-immunoprecipitation, structural interaction modeling, and Ccdc146 knockout mouse analysis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with structural modeling, single study focused on CCDC146 but directly implicates CCDC38 complex\",\n      \"pmids\": [\"38038747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CCDC38 is required for acrosome biogenesis and fibrous sheath assembly in mice; Ccdc38 knockout causes acrosomal hypoplasia with loosely anchored acrosomal membrane, disorganized fibrous sheaths, and decreased/aberrant distribution of TEKT3 (a protein associated with acrosome biogenesis) in testes and sperm.\",\n      \"method\": \"Base-editing-induced Ccdc38 knockout mouse model with ultrastructural and immunofluorescence analysis; ICSI rescue experiment\",\n      \"journal\": \"Journal of genetics and genomics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with multiple orthogonal phenotypic readouts and molecular marker analysis, functional rescue by ICSI\",\n      \"pmids\": [\"37709195\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CCDC38 is a testis-enriched, centrosome- and manchette-associated protein that forms complexes with CCDC42, CCDC146, and IFT88 to facilitate intraflagellar transport of structural cargo (including ODF2) to the growing sperm flagellum, and additionally interacts with TEKT3 and ubiquitinated histone H2A to support acrosome biogenesis and fibrous sheath assembly during spermiogenesis; its loss causes distorted manchette, multiple morphological abnormalities of the flagella (MMAF), acrosomal hypoplasia, and complete male infertility in mice.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CCDC38 is a centrosome- and manchette-associated coiled-coil protein essential for sperm flagellum biogenesis, acrosome formation, and male fertility. During spermiogenesis, CCDC38 forms a complex with CCDC42 and CCDC146 on the manchette and sperm tail, where it interacts with the intraflagellar transport protein IFT88 to facilitate delivery of structural cargo such as ODF2 to the growing flagellum; loss of CCDC38 in mice causes distorted manchette morphology, multiple morphological abnormalities of the flagella (MMAF), acrosomal hypoplasia with disorganized fibrous sheaths, and complete male sterility [PMID:35587122, PMID:38038747, PMID:37709195]. CCDC38 additionally localizes to centrosomes in mammalian cells and interacts with ubiquitinated histone H2A and the structural protein TEKT3 in the testis, linking it to both cytoskeletal organization and chromatin-associated processes during sperm development [PMID:25074808, PMID:27278724, PMID:37709195].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Identification of CCDC38 as a centrosome-associated protein established its connection to the microtubule-organizing center, providing the first subcellular context for its function.\",\n      \"evidence\": \"Mass spectrometry of bovine sperm centrioles followed by localization assessment in cultured mammalian cells\",\n      \"pmids\": [\"25074808\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional assay performed; centrosomal role inferred solely from localization\",\n        \"Relevance to spermatogenesis versus general centrosome biology was unclear\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Discovery of an interaction between CCDC38 and ubiquitinated histone H2A in mouse testes raised the possibility that CCDC38 participates in chromatin-related processes during spermiogenesis, though the functional significance was not resolved.\",\n      \"evidence\": \"Co-immunoprecipitation and immunofluorescence co-localization in mouse testes\",\n      \"pmids\": [\"27278724\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation or functional follow-up\",\n        \"Biological consequence of the H2A interaction remains unknown\",\n        \"No loss-of-function experiment to test requirement\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Knockout studies and interaction mapping established CCDC38 as a manchette- and flagellum-localized protein that complexes with CCDC42 and the IFT component IFT88 to transport ODF2 to the sperm tail, with its loss causing MMAF and male sterility — answering the central question of its physiological function.\",\n      \"evidence\": \"Reciprocal Co-IP identifying CCDC42, IFT88, and ODF2 interactions; Ccdc38 knockout mouse showing distorted manchette, MMAF, reduced ODF2 delivery, and complete infertility\",\n      \"pmids\": [\"35587122\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct biochemical reconstitution of the CCDC38–IFT88 transport complex has not been performed\",\n        \"Whether CCDC38 is a cargo adaptor versus a structural scaffold for IFT remains unresolved\",\n        \"Human genetic validation (MMAF patient mutations in CCDC38) not yet reported\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstration that CCDC146 is a third core member of the CCDC38–CCDC42 complex and that CCDC146 loss reduces IFT88/IFT20 levels without affecting CCDC38 refined the hierarchical assembly of this flagellum-biogenesis module.\",\n      \"evidence\": \"Co-IP and atomic-level interaction modeling of CCDC146–CCDC38; Ccdc146 knockout mouse with IFT protein quantification\",\n      \"pmids\": [\"38038747\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Stoichiometry and assembly order of the trimeric complex are unknown\",\n        \"Whether CCDC38 recruits CCDC146 or vice versa has not been tested by sequential depletion\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"An independent knockout confirmed the flagellar phenotype and extended CCDC38's role to acrosome biogenesis and fibrous sheath assembly, showing acrosomal hypoplasia and aberrant TEKT3 distribution, thereby broadening the functional scope beyond IFT-mediated tail formation.\",\n      \"evidence\": \"Base-editing Ccdc38 knockout mouse with TEM ultrastructure, immunofluorescence for TEKT3, and ICSI fertility rescue\",\n      \"pmids\": [\"37709195\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism linking CCDC38 to acrosomal membrane anchoring is undefined\",\n        \"Whether TEKT3 is a direct physical partner or a downstream marker has not been distinguished\",\n        \"Relationship between the IFT-transport function and acrosome biogenesis function is unclear\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include whether CCDC38 mutations cause human male infertility, how CCDC38 coordinates its dual roles in flagellar IFT and acrosome biogenesis, and the structural basis of the CCDC38–CCDC42–CCDC146 complex.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No human genetic studies linking CCDC38 variants to MMAF or infertility\",\n        \"No structural or cryo-EM data for the trimeric complex\",\n        \"Mechanism coupling manchette-based transport to acrosomal vesicle formation is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0008092\",\n        \"supporting_discovery_ids\": [2, 3, 4]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005815\",\n        \"supporting_discovery_ids\": [0]\n      },\n      {\n        \"term_id\": \"GO:0005856\",\n        \"supporting_discovery_ids\": [2, 5]\n      },\n      {\n        \"term_id\": \"GO:0005929\",\n        \"supporting_discovery_ids\": [2, 3]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1852241\",\n        \"supporting_discovery_ids\": [2, 3, 4, 5]\n      },\n      {\n        \"term_id\": \"R-HSA-1474165\",\n        \"supporting_discovery_ids\": [2, 5]\n      }\n    ],\n    \"complexes\": [\n      \"CCDC38–CCDC42–CCDC146 complex\"\n    ],\n    \"partners\": [\n      \"CCDC42\",\n      \"CCDC146\",\n      \"IFT88\",\n      \"ODF2\",\n      \"TEKT3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}