{"gene":"FBXL13","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2018,"finding":"FBXL13 functions as the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex, localizes to centrosomes, and directly targets CEP192 for proteasomal degradation. FBXL13 also interacts with centrosomal proteins Centrin-2, Centrin-3, and CEP152. Induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays; conversely, depletion of FBXL13 causes elevated CEP192 and γ-tubulin at centrosomes and defects in cell motility.","method":"Co-immunoprecipitation, proteasomal degradation assays, overexpression and knockdown with centrosomal marker quantification (γ-tubulin, CEP192), cell motility assays","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, functional rescue experiments, multiple orthogonal readouts (protein levels, microtubule arrays, cell migration) in a single focused study","pmids":["29348145"],"is_preprint":false},{"year":2020,"finding":"In mice, FBXL13 (DRC6) is a component of the Nexin-Dynein Regulatory Complex (N-DRC) in sperm flagella, interacting with TCTE1 (DRC5) and DRC7. However, Fbxl13 knockout mice show no obvious phenotype, demonstrating that FBXL13 is dispensable for N-DRC assembly and male fertility in mice under normal conditions.","method":"Genetic knockout (Fbxl13 KO mice), fertility assays, electron microscopy of axoneme ultrastructure","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined phenotypic readout (fertility, axoneme structure); finding is explicitly negative for FBXL13 function but establishes its N-DRC localization context","pmids":["31961863"],"is_preprint":false},{"year":2024,"finding":"Immunofluorescence in situ staining in mouse spermatozoa confirmed FBXL13 (DRC6) protein localizes to the sperm flagellum as part of the N-DRC complex, co-localizing with TCTE1 (DRC5), DRC7, and EPS8L1 (DRC3). In Tcte1 knockout mice, FBXL13 protein fails to be transported to the sperm flagella, indicating FBXL13 flagellar localization depends on TCTE1.","method":"Immunofluorescence in situ staining of N-DRC proteins (Tcte1, Drc7, Fbxl13, Eps8l1) in mouse spermatozoa from WT and Tcte1 KO mice","journal":"Human reproduction open","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment with functional context; single lab but corroborates prior N-DRC interaction data from PMID:31961863","pmids":["38650655"],"is_preprint":false}],"current_model":"FBXL13 is a centrosome-enriched F-box protein that acts as the substrate-recognition subunit of an SCF E3 ubiquitin ligase to drive proteasomal degradation of CEP192, thereby controlling centrosomal γ-tubulin levels, microtubule nucleation capacity, and cell motility; it is also a structural component of the Nexin-Dynein Regulatory Complex (N-DRC) in sperm flagella, where its localization depends on TCTE1 (DRC5), though it is dispensable for N-DRC assembly and male fertility in mice."},"narrative":{"mechanistic_narrative":"FBXL13 is a centrosome-enriched F-box protein that serves as the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase, coupling substrate selection to proteasomal degradation in the control of centrosome biology [PMID:29348145]. It directly targets CEP192 for degradation and associates with the centrosomal proteins Centrin-2, Centrin-3, and CEP152; induced FBXL13 expression lowers centrosomal γ-tubulin and disrupts microtubule arrays, whereas its depletion elevates CEP192 and γ-tubulin at centrosomes and impairs cell motility, establishing FBXL13 as a negative regulator of centrosomal microtubule nucleation capacity and migration [PMID:29348145]. In a distinct context, FBXL13 (DRC6) is a component of the Nexin-Dynein Regulatory Complex (N-DRC) of sperm flagella, where its flagellar localization depends on TCTE1 (DRC5) [PMID:38650655]; however, Fbxl13 knockout mice are fertile with normal axoneme ultrastructure, indicating it is dispensable for N-DRC assembly and male fertility under normal conditions [PMID:31961863].","teleology":[{"year":2018,"claim":"Established FBXL13 as a functional SCF E3 ligase substrate receptor and identified CEP192 as its degradation target, defining how FBXL13 restrains centrosomal microtubule nucleation and cell motility.","evidence":"Co-IP, proteasomal degradation assays, and overexpression/knockdown with γ-tubulin and CEP192 quantification plus motility assays in cultured cells","pmids":["29348145"],"confidence":"High","gaps":["Degron/recognition motif on CEP192 not mapped","Functional roles of Centrin-2/Centrin-3/CEP152 interactions not resolved","In vivo requirement for centrosomal function not tested in animals"]},{"year":2020,"claim":"Placed FBXL13 (DRC6) within the flagellar N-DRC and tested its physiological necessity, revealing it is dispensable for N-DRC assembly and male fertility in mice.","evidence":"Fbxl13 knockout mice with fertility assays and electron microscopy of axoneme ultrastructure","pmids":["31961863"],"confidence":"Medium","gaps":["Negative phenotype leaves FBXL13's specific N-DRC role undefined","Possible redundancy or conditional requirement not addressed","Relationship between centrosomal SCF function and flagellar role unexplored"]},{"year":2024,"claim":"Resolved the dependency of FBXL13 flagellar targeting, showing TCTE1 is required to transport FBXL13 into the sperm flagellum.","evidence":"Immunofluorescence in situ staining of N-DRC proteins in WT versus Tcte1 KO mouse spermatozoa","pmids":["38650655"],"confidence":"Medium","gaps":["Single-lab localization study without biochemical reconstitution","Mechanism of TCTE1-dependent transport not defined","Whether FBXL13 retains E3 ligase activity within the flagellum is unknown"]},{"year":null,"claim":"How FBXL13's two reported roles — SCF-mediated CEP192 degradation at the centrosome and structural participation in the flagellar N-DRC — relate mechanistically remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of FBXL13 or its SCF complex","Full substrate repertoire beyond CEP192 unknown","In vivo significance of centrosomal function in mammals untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":["SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase","Nexin-Dynein Regulatory Complex (N-DRC)"],"partners":["CEP192","CEP152","CETN2","CETN3","TCTE1","DRC7","EPS8L1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8NEE6","full_name":"F-box and leucine-rich repeat protein 13","aliases":["Dynein regulatory complex subunit 6","F-box/LRR-repeat protein 13"],"length_aa":735,"mass_kda":83.9,"function":"Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Specifically targets CEP192 isoform 3 for ubiquitin-mediated proteolysis and thereby acts as a regulator of microtubule nucleation activity (PubMed:29348145)","subcellular_location":"Cytoplasm, cytoskeleton, flagellum axoneme; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q8NEE6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FBXL13","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/FBXL13","total_profiled":1310},"omim":[{"mim_id":"618769","title":"DYNEIN REGULATORY COMPLEX SUBUNIT 7; DRC7","url":"https://www.omim.org/entry/618769"},{"mim_id":"609080","title":"F-BOX AND LEUCINE-RICH REPEAT PROTEIN 13; FBXL13","url":"https://www.omim.org/entry/609080"},{"mim_id":"186975","title":"T COMPLEX-ASSOCIATED TESTIS-EXPRESSED 1; TCTE1","url":"https://www.omim.org/entry/186975"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"stomach 1","ntpm":4.8},{"tissue":"testis","ntpm":3.7}],"url":"https://www.proteinatlas.org/search/FBXL13"},"hgnc":{"alias_symbol":["MGC21636","Fbl13","DRC6","CFAP169"],"prev_symbol":[]},"alphafold":{"accession":"Q8NEE6","domains":[{"cath_id":"3.80.10.10","chopping":"415-534","consensus_level":"medium","plddt":96.0658,"start":415,"end":534},{"cath_id":"3.80.10.10","chopping":"538-708","consensus_level":"medium","plddt":94.2906,"start":538,"end":708}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NEE6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NEE6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NEE6-F1-predicted_aligned_error_v6.png","plddt_mean":88.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FBXL13","jax_strain_url":"https://www.jax.org/strain/search?query=FBXL13"},"sequence":{"accession":"Q8NEE6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8NEE6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8NEE6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NEE6"}},"corpus_meta":[{"pmid":"15820312","id":"PMC_15820312","title":"Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22.","date":"2005","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/15820312","citation_count":41,"is_preprint":false},{"pmid":"31961863","id":"PMC_31961863","title":"Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice.","date":"2020","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31961863","citation_count":40,"is_preprint":false},{"pmid":"27889101","id":"PMC_27889101","title":"Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome sequencing and genome-wide arrays.","date":"2016","source":"Fertility and sterility","url":"https://pubmed.ncbi.nlm.nih.gov/27889101","citation_count":38,"is_preprint":false},{"pmid":"29348145","id":"PMC_29348145","title":"FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration.","date":"2018","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/29348145","citation_count":26,"is_preprint":false},{"pmid":"33428145","id":"PMC_33428145","title":"Identification of Serum Exosomal MicroRNA Expression Profiling in Menopausal Females with Osteoporosis by High-throughput Sequencing.","date":"2021","source":"Current medical science","url":"https://pubmed.ncbi.nlm.nih.gov/33428145","citation_count":24,"is_preprint":false},{"pmid":"35023977","id":"PMC_35023977","title":"Genome-Wide Association Study and Genetic Correlation Scan Provide Insights into Its Genetic Architecture of Sleep Health Score in the UK Biobank Cohort.","date":"2022","source":"Nature and science of sleep","url":"https://pubmed.ncbi.nlm.nih.gov/35023977","citation_count":19,"is_preprint":false},{"pmid":"25649863","id":"PMC_25649863","title":"Identifying genetic interactions associated with late-onset Alzheimer's disease.","date":"2014","source":"BioData mining","url":"https://pubmed.ncbi.nlm.nih.gov/25649863","citation_count":17,"is_preprint":false},{"pmid":"29257106","id":"PMC_29257106","title":"A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder.","date":"2017","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29257106","citation_count":11,"is_preprint":false},{"pmid":"26456453","id":"PMC_26456453","title":"Quantification of African cassava mosaic virus (ACMV) and East African cassava mosaic virus (EACMV-UG) in single and mixed infected Cassava (Manihot esculenta Crantz) using quantitative PCR.","date":"2015","source":"Journal of virological methods","url":"https://pubmed.ncbi.nlm.nih.gov/26456453","citation_count":4,"is_preprint":false},{"pmid":"38650655","id":"PMC_38650655","title":"Effects of Tcte1 knockout on energy chain transportation and spermatogenesis: implications for male infertility.","date":"2024","source":"Human reproduction open","url":"https://pubmed.ncbi.nlm.nih.gov/38650655","citation_count":1,"is_preprint":false},{"pmid":"40341176","id":"PMC_40341176","title":"OTX2 expression contributes progression of gastric cancer in young adults.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40341176","citation_count":1,"is_preprint":false},{"pmid":"42256732","id":"PMC_42256732","title":"Genome-wide genetic characterization and selection signatures in Anatolian Merino sheep.","date":"2025","source":"Archives animal breeding","url":"https://pubmed.ncbi.nlm.nih.gov/42256732","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9531,"output_tokens":1068,"usd":0.022306,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7542,"output_tokens":1784,"usd":0.041155,"stage2_stop_reason":"end_turn"},"total_usd":0.063461,"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\": 2018,\n      \"finding\": \"FBXL13 functions as the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex, localizes to centrosomes, and directly targets CEP192 for proteasomal degradation. FBXL13 also interacts with centrosomal proteins Centrin-2, Centrin-3, and CEP152. Induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays; conversely, depletion of FBXL13 causes elevated CEP192 and γ-tubulin at centrosomes and defects in cell motility.\",\n      \"method\": \"Co-immunoprecipitation, proteasomal degradation assays, overexpression and knockdown with centrosomal marker quantification (γ-tubulin, CEP192), cell motility assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, functional rescue experiments, multiple orthogonal readouts (protein levels, microtubule arrays, cell migration) in a single focused study\",\n      \"pmids\": [\"29348145\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In mice, FBXL13 (DRC6) is a component of the Nexin-Dynein Regulatory Complex (N-DRC) in sperm flagella, interacting with TCTE1 (DRC5) and DRC7. However, Fbxl13 knockout mice show no obvious phenotype, demonstrating that FBXL13 is dispensable for N-DRC assembly and male fertility in mice under normal conditions.\",\n      \"method\": \"Genetic knockout (Fbxl13 KO mice), fertility assays, electron microscopy of axoneme ultrastructure\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined phenotypic readout (fertility, axoneme structure); finding is explicitly negative for FBXL13 function but establishes its N-DRC localization context\",\n      \"pmids\": [\"31961863\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Immunofluorescence in situ staining in mouse spermatozoa confirmed FBXL13 (DRC6) protein localizes to the sperm flagellum as part of the N-DRC complex, co-localizing with TCTE1 (DRC5), DRC7, and EPS8L1 (DRC3). In Tcte1 knockout mice, FBXL13 protein fails to be transported to the sperm flagella, indicating FBXL13 flagellar localization depends on TCTE1.\",\n      \"method\": \"Immunofluorescence in situ staining of N-DRC proteins (Tcte1, Drc7, Fbxl13, Eps8l1) in mouse spermatozoa from WT and Tcte1 KO mice\",\n      \"journal\": \"Human reproduction open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment with functional context; single lab but corroborates prior N-DRC interaction data from PMID:31961863\",\n      \"pmids\": [\"38650655\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FBXL13 is a centrosome-enriched F-box protein that acts as the substrate-recognition subunit of an SCF E3 ubiquitin ligase to drive proteasomal degradation of CEP192, thereby controlling centrosomal γ-tubulin levels, microtubule nucleation capacity, and cell motility; it is also a structural component of the Nexin-Dynein Regulatory Complex (N-DRC) in sperm flagella, where its localization depends on TCTE1 (DRC5), though it is dispensable for N-DRC assembly and male fertility in mice.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FBXL13 is a centrosome-enriched F-box protein that serves as the substrate-recognition subunit of an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase, coupling substrate selection to proteasomal degradation in the control of centrosome biology [#0]. It directly targets CEP192 for degradation and associates with the centrosomal proteins Centrin-2, Centrin-3, and CEP152; induced FBXL13 expression lowers centrosomal \\u03b3-tubulin and disrupts microtubule arrays, whereas its depletion elevates CEP192 and \\u03b3-tubulin at centrosomes and impairs cell motility, establishing FBXL13 as a negative regulator of centrosomal microtubule nucleation capacity and migration [#0]. In a distinct context, FBXL13 (DRC6) is a component of the Nexin-Dynein Regulatory Complex (N-DRC) of sperm flagella, where its flagellar localization depends on TCTE1 (DRC5) [#2]; however, Fbxl13 knockout mice are fertile with normal axoneme ultrastructure, indicating it is dispensable for N-DRC assembly and male fertility under normal conditions [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established FBXL13 as a functional SCF E3 ligase substrate receptor and identified CEP192 as its degradation target, defining how FBXL13 restrains centrosomal microtubule nucleation and cell motility.\",\n      \"evidence\": \"Co-IP, proteasomal degradation assays, and overexpression/knockdown with \\u03b3-tubulin and CEP192 quantification plus motility assays in cultured cells\",\n      \"pmids\": [\"29348145\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Degron/recognition motif on CEP192 not mapped\",\n        \"Functional roles of Centrin-2/Centrin-3/CEP152 interactions not resolved\",\n        \"In vivo requirement for centrosomal function not tested in animals\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placed FBXL13 (DRC6) within the flagellar N-DRC and tested its physiological necessity, revealing it is dispensable for N-DRC assembly and male fertility in mice.\",\n      \"evidence\": \"Fbxl13 knockout mice with fertility assays and electron microscopy of axoneme ultrastructure\",\n      \"pmids\": [\"31961863\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Negative phenotype leaves FBXL13's specific N-DRC role undefined\",\n        \"Possible redundancy or conditional requirement not addressed\",\n        \"Relationship between centrosomal SCF function and flagellar role unexplored\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolved the dependency of FBXL13 flagellar targeting, showing TCTE1 is required to transport FBXL13 into the sperm flagellum.\",\n      \"evidence\": \"Immunofluorescence in situ staining of N-DRC proteins in WT versus Tcte1 KO mouse spermatozoa\",\n      \"pmids\": [\"38650655\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab localization study without biochemical reconstitution\",\n        \"Mechanism of TCTE1-dependent transport not defined\",\n        \"Whether FBXL13 retains E3 ligase activity within the flagellum is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How FBXL13's two reported roles \\u2014 SCF-mediated CEP192 degradation at the centrosome and structural participation in the flagellar N-DRC \\u2014 relate mechanistically remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of FBXL13 or its SCF complex\",\n        \"Full substrate repertoire beyond CEP192 unknown\",\n        \"In vivo significance of centrosomal function in mammals untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase\", \"Nexin-Dynein Regulatory Complex (N-DRC)\"],\n    \"partners\": [\"CEP192\", \"CEP152\", \"CETN2\", \"CETN3\", \"TCTE1\", \"DRC7\", \"EPS8L1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}