{"gene":"EFCAB5","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2025,"finding":"EFCAB5 was identified as a sperm-specific CFAP91-proximal component via proximity labeling (BioID2) in mature spermatozoa, and Efcab5 knockout males exhibit reduced sperm motility and fertility, establishing EFCAB5 as a sperm-specialized movement regulator within the axonemal/radial spoke framework.","method":"Proximity labeling (BioID2-tagged CFAP91 in transgenic mice), Efcab5 knockout mouse model with sperm motility and fertility readouts","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity labeling plus KO phenotype with defined functional readout (motility, fertility), single lab, two orthogonal methods","pmids":["40931011"],"is_preprint":false}],"current_model":"EFCAB5 is a sperm-specific axonemal component that localizes in proximity to the radial spoke 3 protein CFAP91 and is required for normal sperm motility and male fertility in mice, as demonstrated by proximity labeling and knockout studies."},"narrative":{"mechanistic_narrative":"EFCAB5 is a sperm-specialized axonemal component required for normal sperm motility and male fertility [PMID:40931011]. It was identified as a CFAP91-proximal protein in mature spermatozoa, placing it within the radial spoke/axonemal framework, and loss of EFCAB5 in mice reduces sperm motility and fertility [PMID:40931011]. Beyond this proximity relationship and knockout phenotype [PMID:40931011], no further mechanistic detail—including direct binding partners, molecular activity, or the structural basis of its role in flagellar movement—has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether EFCAB5 has a defined role in sperm function was unknown; proximity labeling and knockout established it as an axonemal motility regulator near the radial spoke protein CFAP91.","evidence":"BioID2 proximity labeling with CFAP91 in transgenic mice plus Efcab5 knockout mouse with sperm motility and fertility readouts","pmids":["40931011"],"confidence":"Medium","gaps":["Direct physical interaction with CFAP91 not demonstrated (proximity labeling only, no reciprocal Co-IP or reconstitution)","Molecular activity of EFCAB5 and its structural placement within the radial spoke unresolved","Mechanism by which loss reduces motility (specific flagellar defect) not defined"]},{"year":null,"claim":"The biochemical function of EFCAB5 and its direct molecular partners within the axoneme remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct binding partner confirmed","No structural or biochemical activity characterized","Human fertility relevance not established"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[0]}],"complexes":[],"partners":["CFAP91"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A4FU69","full_name":"EF-hand calcium-binding domain-containing protein 5","aliases":[],"length_aa":1503,"mass_kda":173.4,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/A4FU69/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EFCAB5","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/EFCAB5","total_profiled":1310},"omim":[{"mim_id":"602463","title":"DIHYDROPYRIMIDINASE-LIKE 2; DPYSL2","url":"https://www.omim.org/entry/602463"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear bodies","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":8.0}],"url":"https://www.proteinatlas.org/search/EFCAB5"},"hgnc":{"alias_symbol":["FLJ46247"],"prev_symbol":[]},"alphafold":{"accession":"A4FU69","domains":[{"cath_id":"-","chopping":"168-197_208-244","consensus_level":"medium","plddt":71.4436,"start":168,"end":244},{"cath_id":"-","chopping":"772-805_851-882_885-965","consensus_level":"medium","plddt":82.8235,"start":772,"end":965},{"cath_id":"3.30.450.40","chopping":"970-1158","consensus_level":"medium","plddt":89.7979,"start":970,"end":1158},{"cath_id":"1.20.920","chopping":"1311-1358_1368-1503","consensus_level":"medium","plddt":75.4052,"start":1311,"end":1503}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A4FU69","model_url":"https://alphafold.ebi.ac.uk/files/AF-A4FU69-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A4FU69-F1-predicted_aligned_error_v6.png","plddt_mean":67.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EFCAB5","jax_strain_url":"https://www.jax.org/strain/search?query=EFCAB5"},"sequence":{"accession":"A4FU69","fasta_url":"https://rest.uniprot.org/uniprotkb/A4FU69.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A4FU69/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A4FU69"}},"corpus_meta":[{"pmid":"28516910","id":"PMC_28516910","title":"Genetic architecture of epigenetic and neuronal ageing rates in human brain regions.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28516910","citation_count":84,"is_preprint":false},{"pmid":"35049806","id":"PMC_35049806","title":"Gene-Set Enrichment Analysis for Identifying Genes and Biological Activities Associated with Growth Traits in Dromedaries.","date":"2022","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/35049806","citation_count":4,"is_preprint":false},{"pmid":"38967597","id":"PMC_38967597","title":"Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis.","date":"2024","source":"Hepatology communications","url":"https://pubmed.ncbi.nlm.nih.gov/38967597","citation_count":4,"is_preprint":false},{"pmid":"40931011","id":"PMC_40931011","title":"Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40931011","citation_count":1,"is_preprint":false},{"pmid":"39987414","id":"PMC_39987414","title":"Clinical implications and molecular mechanism of long noncoding RNA LINC00518 and protein-coding genes in skin cutaneous melanoma by genome‑wide investigation.","date":"2025","source":"Archives of dermatological research","url":"https://pubmed.ncbi.nlm.nih.gov/39987414","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4836,"output_tokens":323,"usd":0.009676,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6544,"output_tokens":822,"usd":0.026635,"stage2_stop_reason":"end_turn"},"total_usd":0.036311,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"EFCAB5 was identified as a sperm-specific CFAP91-proximal component via proximity labeling (BioID2) in mature spermatozoa, and Efcab5 knockout males exhibit reduced sperm motility and fertility, establishing EFCAB5 as a sperm-specialized movement regulator within the axonemal/radial spoke framework.\",\n      \"method\": \"Proximity labeling (BioID2-tagged CFAP91 in transgenic mice), Efcab5 knockout mouse model with sperm motility and fertility readouts\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labeling plus KO phenotype with defined functional readout (motility, fertility), single lab, two orthogonal methods\",\n      \"pmids\": [\"40931011\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EFCAB5 is a sperm-specific axonemal component that localizes in proximity to the radial spoke 3 protein CFAP91 and is required for normal sperm motility and male fertility in mice, as demonstrated by proximity labeling and knockout studies.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EFCAB5 is a sperm-specialized axonemal component required for normal sperm motility and male fertility [#0]. It was identified as a CFAP91-proximal protein in mature spermatozoa, placing it within the radial spoke/axonemal framework, and loss of EFCAB5 in mice reduces sperm motility and fertility [#0]. Beyond this proximity relationship and knockout phenotype [#0], no further mechanistic detail—including direct binding partners, molecular activity, or the structural basis of its role in flagellar movement—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether EFCAB5 has a defined role in sperm function was unknown; proximity labeling and knockout established it as an axonemal motility regulator near the radial spoke protein CFAP91.\",\n      \"evidence\": \"BioID2 proximity labeling with CFAP91 in transgenic mice plus Efcab5 knockout mouse with sperm motility and fertility readouts\",\n      \"pmids\": [\"40931011\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct physical interaction with CFAP91 not demonstrated (proximity labeling only, no reciprocal Co-IP or reconstitution)\",\n        \"Molecular activity of EFCAB5 and its structural placement within the radial spoke unresolved\",\n        \"Mechanism by which loss reduces motility (specific flagellar defect) not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical function of EFCAB5 and its direct molecular partners within the axoneme remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct binding partner confirmed\",\n        \"No structural or biochemical activity characterized\",\n        \"Human fertility relevance not established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005930\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CFAP91\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}