{"gene":"CEP295NL","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2009,"finding":"CEP295NL (DDC8) was identified as a binding partner of the testis-specific protein Trs4 (IQUB homolog/related) in mouse testes; the interaction was confirmed by yeast two-hybrid, in vivo co-immunoprecipitation, and in vitro binding assays. CEP295NL protein co-localizes with Trs4 and Rshl-2 to the tails of mature spermatozoa and displays a similar testicular expression pattern to Trs4.","method":"Yeast two-hybrid screening, co-immunoprecipitation (in vivo), in vitro binding assay, co-localization by immunofluorescence","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal/orthogonal binding assays (Y2H + CoIP + in vitro), single lab","pmids":["19706271"],"is_preprint":false},{"year":2023,"finding":"CEP295NL (DDC8) interacts with IQUB, RSPH3, GSTM1, and ODF1 in the yeast two-hybrid system, placing CEP295NL in a sperm axoneme/radial spoke protein complex relevant to sperm motility.","method":"Yeast two-hybrid protein interaction assay","journal":"Human reproduction (Oxford, England)","confidence":"Low","confidence_rationale":"Tier 3 — single method (yeast two-hybrid only), interaction not independently validated by biochemical pulldown for CEP295NL specifically","pmids":["36355624"],"is_preprint":false}],"current_model":"CEP295NL (DDC8) is a testis/spermatogenesis-expressed protein that localizes to the tails of mature spermatozoa and participates in a multi-protein complex at the sperm axoneme, physically interacting with IQUB (Trs4), RSPH3, GSTM1, and ODF1, suggesting a role in radial spoke assembly and sperm motility."},"narrative":{"teleology":[{"year":2009,"claim":"The first functional link for CEP295NL was established by showing it directly binds the testis-specific protein Trs4 (IQUB homolog) and co-localizes with Trs4 and Rshl-2 on sperm tails, placing this otherwise uncharacterized protein in a flagellar context.","evidence":"Yeast two-hybrid, co-immunoprecipitation, in vitro binding, and immunofluorescence co-localization in mouse testes and spermatozoa","pmids":["19706271"],"confidence":"Medium","gaps":["No loss-of-function data to determine whether CEP295NL is required for sperm motility or fertility","Interaction validated only in mouse; human relevance not directly tested","Precise sub-structural localization within the axoneme (e.g., radial spoke head vs. stalk) not resolved"]},{"year":2023,"claim":"CEP295NL was placed in a broader protein interaction network by demonstrating yeast two-hybrid interactions with RSPH3, ODF1, and GSTM1 in addition to IQUB, linking it to the radial spoke complex and outer dense fibers of the sperm axoneme.","evidence":"Yeast two-hybrid interaction assay","pmids":["36355624"],"confidence":"Low","gaps":["Interactions with RSPH3, ODF1, and GSTM1 detected by yeast two-hybrid only; no reciprocal co-immunoprecipitation or pulldown validation","Functional consequence of these interactions on sperm motility or flagellar structure not tested","No structural or stoichiometric characterization of the putative complex"]},{"year":null,"claim":"It remains unknown whether CEP295NL is essential for spermatogenesis, sperm motility, or male fertility, and no knockout or patient mutation data exist to define its physiological requirement.","evidence":"","pmids":[],"confidence":"Low","gaps":["No gene knockout or knockdown phenotype reported","No association with human male infertility or ciliopathy established","Mechanism by which CEP295NL contributes to radial spoke or outer dense fiber function is entirely uncharacterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["IQUB","RSPH3","ODF1"],"other_free_text":[]},"mechanistic_narrative":"CEP295NL (also known as DDC8) is a testis-expressed protein that localizes to the tails of mature spermatozoa, where it physically interacts with the axonemal/radial spoke proteins IQUB (Trs4), RSPH3, ODF1, and GSTM1, implicating it in sperm flagellar assembly or motility [PMID:19706271, PMID:36355624]. Its interaction with IQUB was confirmed by yeast two-hybrid, co-immunoprecipitation, and in vitro binding assays in mouse testis, and the two proteins co-localize along the sperm tail [PMID:19706271]."},"prefetch_data":{"uniprot":{"accession":"Q96MC4","full_name":"CEP295 N-terminal-like protein","aliases":["KIAA1731 N-terminal like protein"],"length_aa":621,"mass_kda":69.8,"function":"","subcellular_location":"Cell projection, cilium","url":"https://www.uniprot.org/uniprotkb/Q96MC4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP295NL","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/CEP295NL","total_profiled":1310},"omim":[{"mim_id":"620557","title":"IQ MOTIF- AND UBIQUITIN DOMAIN-CONTAINING PROTEIN; IQUB","url":"https://www.omim.org/entry/620557"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":26.1}],"url":"https://www.proteinatlas.org/search/CEP295NL"},"hgnc":{"alias_symbol":["DDC8"],"prev_symbol":["KIAA1731NL"]},"alphafold":{"accession":"Q96MC4","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MC4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MC4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MC4-F1-predicted_aligned_error_v6.png","plddt_mean":57.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP295NL","jax_strain_url":"https://www.jax.org/strain/search?query=CEP295NL"},"sequence":{"accession":"Q96MC4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96MC4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96MC4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MC4"}},"corpus_meta":[{"pmid":"16985004","id":"PMC_16985004","title":"Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2.","date":"2006","source":"Physiological genomics","url":"https://pubmed.ncbi.nlm.nih.gov/16985004","citation_count":19,"is_preprint":false},{"pmid":"9237247","id":"PMC_9237247","title":"Differential display to identify and isolate novel genes expressed during spermatogenesis.","date":"1997","source":"Molecular human reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/9237247","citation_count":14,"is_preprint":false},{"pmid":"36355624","id":"PMC_36355624","title":"IQUB deficiency causes male infertility by affecting the activity of p-ERK1/2/RSPH3.","date":"2023","source":"Human reproduction (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/36355624","citation_count":8,"is_preprint":false},{"pmid":"19706271","id":"PMC_19706271","title":"Male germ cell-specific protein Trs4 binds to multiple proteins.","date":"2009","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/19706271","citation_count":7,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3744,"output_tokens":586,"usd":0.010011},"stage2":{"model":"claude-opus-4-6","input_tokens":3750,"output_tokens":965,"usd":0.064312},"total_usd":0.074323,"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\": 2009,\n      \"finding\": \"CEP295NL (DDC8) was identified as a binding partner of the testis-specific protein Trs4 (IQUB homolog/related) in mouse testes; the interaction was confirmed by yeast two-hybrid, in vivo co-immunoprecipitation, and in vitro binding assays. CEP295NL protein co-localizes with Trs4 and Rshl-2 to the tails of mature spermatozoa and displays a similar testicular expression pattern to Trs4.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation (in vivo), in vitro binding assay, co-localization by immunofluorescence\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal/orthogonal binding assays (Y2H + CoIP + in vitro), single lab\",\n      \"pmids\": [\"19706271\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CEP295NL (DDC8) interacts with IQUB, RSPH3, GSTM1, and ODF1 in the yeast two-hybrid system, placing CEP295NL in a sperm axoneme/radial spoke protein complex relevant to sperm motility.\",\n      \"method\": \"Yeast two-hybrid protein interaction assay\",\n      \"journal\": \"Human reproduction (Oxford, England)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single method (yeast two-hybrid only), interaction not independently validated by biochemical pulldown for CEP295NL specifically\",\n      \"pmids\": [\"36355624\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CEP295NL (DDC8) is a testis/spermatogenesis-expressed protein that localizes to the tails of mature spermatozoa and participates in a multi-protein complex at the sperm axoneme, physically interacting with IQUB (Trs4), RSPH3, GSTM1, and ODF1, suggesting a role in radial spoke assembly and sperm motility.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CEP295NL (also known as DDC8) is a testis-expressed protein that localizes to the tails of mature spermatozoa, where it physically interacts with the axonemal/radial spoke proteins IQUB (Trs4), RSPH3, ODF1, and GSTM1, implicating it in sperm flagellar assembly or motility [PMID:19706271, PMID:36355624]. Its interaction with IQUB was confirmed by yeast two-hybrid, co-immunoprecipitation, and in vitro binding assays in mouse testis, and the two proteins co-localize along the sperm tail [PMID:19706271].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"The first functional link for CEP295NL was established by showing it directly binds the testis-specific protein Trs4 (IQUB homolog) and co-localizes with Trs4 and Rshl-2 on sperm tails, placing this otherwise uncharacterized protein in a flagellar context.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, in vitro binding, and immunofluorescence co-localization in mouse testes and spermatozoa\",\n      \"pmids\": [\"19706271\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No loss-of-function data to determine whether CEP295NL is required for sperm motility or fertility\",\n        \"Interaction validated only in mouse; human relevance not directly tested\",\n        \"Precise sub-structural localization within the axoneme (e.g., radial spoke head vs. stalk) not resolved\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"CEP295NL was placed in a broader protein interaction network by demonstrating yeast two-hybrid interactions with RSPH3, ODF1, and GSTM1 in addition to IQUB, linking it to the radial spoke complex and outer dense fibers of the sperm axoneme.\",\n      \"evidence\": \"Yeast two-hybrid interaction assay\",\n      \"pmids\": [\"36355624\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Interactions with RSPH3, ODF1, and GSTM1 detected by yeast two-hybrid only; no reciprocal co-immunoprecipitation or pulldown validation\",\n        \"Functional consequence of these interactions on sperm motility or flagellar structure not tested\",\n        \"No structural or stoichiometric characterization of the putative complex\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether CEP295NL is essential for spermatogenesis, sperm motility, or male fertility, and no knockout or patient mutation data exist to define its physiological requirement.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No gene knockout or knockdown phenotype reported\",\n        \"No association with human male infertility or ciliopathy established\",\n        \"Mechanism by which CEP295NL contributes to radial spoke or outer dense fiber function is entirely uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005929\",\n        \"supporting_discovery_ids\": [0, 1]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1474165\",\n        \"supporting_discovery_ids\": [0, 1]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\"IQUB\", \"RSPH3\", \"ODF1\"],\n    \"other_free_text\": []\n  }\n}\n```"}