{"gene":"DRC7","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2011,"finding":"CG34110/Ccdc135/FAP50 (DRC7 ortholog) localizes along the sperm flagellum in Drosophila and is tightly associated with outer doublet microtubules of the axoneme; it does not appear to be a component of the central pair, radial spokes, dynein arms, or structures defined by mbo waveform mutants. Loss-of-function of the Drosophila ortholog (lobo mutation) specifically impairs sperm movement into the female storage receptacle, and genetic analyses place it in the same pathway as Pkd2 (polycystin-2 calcium channel).","method":"Genetic screen (EMS mutagenesis), loss-of-function phenotypic analysis, subcellular localization by immunofluorescence, axonemal fractionation/biochemical association studies in Chlamydomonas (FAP50)","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by fractionation and immunofluorescence plus genetic epistasis with Pkd2 in a single lab, but ortholog-based (Drosophila/Chlamydomonas), not direct study of mammalian DRC7","pmids":["21289096"],"is_preprint":false},{"year":2020,"finding":"DRC7 is required for correct assembly of the Nexin-Dynein Regulatory Complex (N-DRC) and for flagellum formation in mice. Drc7 knockout males are infertile due to short, immotile spermatozoa. In Drc7 KO spermatids, the axoneme is disorganized and the '9+2' microtubule arrangement is disrupted. Critically, other N-DRC components fail to incorporate into the flagellum in the absence of DRC7, establishing DRC7 as essential for N-DRC assembly.","method":"Knockout mouse model (Drc7 KO), transmission electron microscopy of axoneme ultrastructure, immunofluorescence of N-DRC components in flagella of KO vs. WT spermatids","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with defined ultrastructural and assembly phenotype, multiple N-DRC components assessed, replicated across multiple analyses in a single rigorous study","pmids":["31961863"],"is_preprint":false},{"year":2020,"finding":"DRC7 interacts with TCTE1 (DRC5) and FBXL13 (DRC6) within the N-DRC; FBXL13 knockout mice show no obvious phenotype, indicating FBXL13 is dispensable, whereas DRC7 is essential, placing DRC7 as a core structural component of the N-DRC required for flagellar axoneme integrity.","method":"Knockout mouse models (Fbxl13 KO and Drc7 KO), phenotypic comparison, previously reported protein interaction data cited in the paper","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via KO comparison establishes DRC7 as essential and FBXL13 as dispensable; interaction with TCTE1/FBXL13 is cited from prior work rather than demonstrated here directly","pmids":["31961863"],"is_preprint":false},{"year":2024,"finding":"In Tcte1 (Drc5) knockout mice, DRC7 protein (along with other N-DRC components Fbxl13/DRC6 and Eps8l1/DRC3) fails to be transported to the sperm flagella, demonstrating that DRC5/TCTE1 is required upstream of DRC7 for proper N-DRC assembly and localization in the flagellum.","method":"Immunofluorescence in situ staining of N-DRC proteins (including DRC7) in spermatozoa from Tcte1 KO vs. WT mice","journal":"Human reproduction open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct immunofluorescence localization experiment with clear loss-of-function readout in a single lab study; establishes epistatic relationship between DRC5 and DRC7 localization","pmids":["38650655"],"is_preprint":false},{"year":2025,"finding":"Drc7 knockout mice on a purebred genetic background show that DRC7 is crucial for survival and, in mixed-background mice, for the motility of ependymal cilia, respiratory cilia, and the stability of sperm flagellar axonemes. DRC7 is identified as a core N-DRC component required for N-DRC assembly, consistent with prior findings. Additionally, in the context of N-DRC defects, AKAP3 was found to play a novel role in regulating sperm phosphorylation.","method":"Drc7 knockout mice (alongside Drc1-4 KOs), motility assays of cilia/flagella, axoneme ultrastructure analysis","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic KO study with defined phenotypic readouts across multiple ciliated tissues; single lab, replicates and extends prior DRC7 KO findings","pmids":["40089458"],"is_preprint":false}],"current_model":"DRC7 (CCDC135/FAP50/CFAP50) is a core structural component of the Nexin-Dynein Regulatory Complex (N-DRC) that associates with outer doublet microtubules of the axoneme; it is required for N-DRC assembly (other N-DRC subunits fail to incorporate into flagella without it), for the stability of the 9+2 axonemal microtubule arrangement in sperm, and for motility of sperm flagella and airway/ependymal cilia, with its own flagellar localization depending on upstream DRC5/TCTE1."},"narrative":{"mechanistic_narrative":"DRC7 (CCDC135/FAP50/CFAP50) is a core structural subunit of the Nexin-Dynein Regulatory Complex (N-DRC) that associates with the outer doublet microtubules of the motile axoneme and is essential for ciliary and flagellar motility [PMID:21289096, PMID:31961863]. It serves as an organizing component of the N-DRC: in its absence other N-DRC subunits fail to incorporate into the flagellum, and the 9+2 axonemal microtubule arrangement becomes disorganized, producing short, immotile sperm and male infertility in knockout mice [PMID:31961863]. Within the complex DRC7 functions alongside TCTE1 (DRC5) and FBXL13 (DRC6), and unlike the dispensable FBXL13, DRC7 is required for axonemal integrity; its own flagellar delivery depends on DRC5/TCTE1 acting upstream [PMID:31961863, PMID:38650655]. Beyond sperm, DRC7 is required for the motility of ependymal and respiratory cilia and for organismal survival on a purebred background, establishing a broad role across motile ciliated tissues [PMID:40089458]. The molecular basis by which DRC7 nucleates N-DRC assembly and contacts individual subunits has not been structurally characterized in the available corpus.","teleology":[{"year":2011,"claim":"Established that the DRC7 ortholog is an axonemal protein physically tied to outer doublet microtubules and required for sperm motility, distinguishing it from central pair, radial spoke, and dynein arm structures.","evidence":"EMS genetic screen, immunofluorescence localization, and axonemal fractionation in Drosophila and Chlamydomonas orthologs (FAP50), with genetic epistasis to Pkd2","pmids":["21289096"],"confidence":"Medium","gaps":["Ortholog-based, not direct study of mammalian DRC7","Molecular function within the axoneme undefined","Mechanistic link to Pkd2 calcium signaling not resolved"]},{"year":2020,"claim":"Demonstrated in mammals that DRC7 is essential for N-DRC assembly itself, since other N-DRC subunits fail to incorporate into the flagellum without it, explaining the disrupted 9+2 axoneme and infertility phenotype.","evidence":"Drc7 knockout mouse, transmission electron microscopy of axoneme ultrastructure, immunofluorescence of N-DRC components in KO vs WT spermatids","pmids":["31961863"],"confidence":"High","gaps":["Direct binding interfaces between DRC7 and other subunits not mapped","No structural model of DRC7 within the N-DRC","Whether assembly defect is nucleation vs stabilization unresolved"]},{"year":2020,"claim":"Placed DRC7 as a core, indispensable subunit relative to other N-DRC members by showing FBXL13 (DRC6) is dispensable while DRC7 is essential, and situating DRC7's interactions with TCTE1 and FBXL13.","evidence":"Comparative phenotyping of Fbxl13 KO and Drc7 KO mice; interaction with TCTE1/FBXL13 cited from prior work","pmids":["31961863"],"confidence":"Medium","gaps":["Direct DRC7-TCTE1/FBXL13 interactions cited rather than demonstrated here","Stoichiometry within the complex unknown"]},{"year":2024,"claim":"Resolved the order of N-DRC assembly by showing DRC5/TCTE1 acts upstream of DRC7, controlling its transport into the flagellum.","evidence":"In situ immunofluorescence of N-DRC proteins including DRC7 in Tcte1 KO vs WT spermatozoa","pmids":["38650655"],"confidence":"Medium","gaps":["Mechanism of DRC7 transport/recruitment not defined","Single-lab localization readout","Whether dependence is direct or indirect unresolved"]},{"year":2025,"claim":"Extended DRC7's role beyond sperm to motile cilia generally, showing it is required for ependymal and respiratory ciliary motility, axoneme stability, and survival, with phosphoregulatory consequences via AKAP3.","evidence":"Drc7 knockout mice on purebred and mixed backgrounds, motility assays across ciliated tissues, axoneme ultrastructure analysis","pmids":["40089458"],"confidence":"Medium","gaps":["Role of AKAP3 phosphoregulation in N-DRC defects not fully mechanistic","Cause of lethality on purebred background unspecified","Tissue-specific requirements not dissected"]},{"year":null,"claim":"How DRC7 structurally nucleates the N-DRC and physically engages each subunit, and the molecular basis of its dependence on DRC5/TCTE1 for flagellar delivery, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No high-resolution structure of DRC7 in the N-DRC","Direct binding partners not biochemically mapped in mammals","Transport machinery delivering DRC7 to the axoneme unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[4]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,4]}],"complexes":["Nexin-Dynein Regulatory Complex (N-DRC)","axoneme"],"partners":["TCTE1","FBXL13"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IY82","full_name":"Dynein regulatory complex subunit 7","aliases":["Coiled-coil domain-containing protein 135","Coiled-coil domain-containing protein lobo homolog"],"length_aa":874,"mass_kda":103.5,"function":"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 (By similarity). Involved in the regulation of flagellar motility (By similarity). Essential for male fertility, sperm head morphogenesis and sperm flagellum formation (By similarity)","subcellular_location":"Cell projection, cilium, flagellum; Cytoplasm, cytoskeleton, cilium axoneme; Cytoplasm, cytoskeleton, flagellum axoneme","url":"https://www.uniprot.org/uniprotkb/Q8IY82/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DRC7","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DRC7","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":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"choroid plexus","ntpm":11.7},{"tissue":"fallopian tube","ntpm":19.8},{"tissue":"testis","ntpm":43.1}],"url":"https://www.proteinatlas.org/search/DRC7"},"hgnc":{"alias_symbol":["DKFZp434I099","FAP50","CFAP50"],"prev_symbol":["C16orf50","CCDC135"]},"alphafold":{"accession":"Q8IY82","domains":[{"cath_id":"3.10.620,3.10.620","chopping":"91-219_296-374","consensus_level":"medium","plddt":91.5026,"start":91,"end":374},{"cath_id":"-","chopping":"484-570_581-709","consensus_level":"medium","plddt":90.5947,"start":484,"end":709},{"cath_id":"-","chopping":"752-874","consensus_level":"high","plddt":82.5484,"start":752,"end":874}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY82","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY82-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY82-F1-predicted_aligned_error_v6.png","plddt_mean":82.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DRC7","jax_strain_url":"https://www.jax.org/strain/search?query=DRC7"},"sequence":{"accession":"Q8IY82","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IY82.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IY82/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY82"}},"corpus_meta":[{"pmid":"21289096","id":"PMC_21289096","title":"Regulation of flagellar motility by the conserved flagellar protein CG34110/Ccdc135/FAP50.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/21289096","citation_count":43,"is_preprint":false},{"pmid":"22983010","id":"PMC_22983010","title":"Novel transglutaminase-like peptidase and C2 domains elucidate the structure, biogenesis and evolution of the ciliary compartment.","date":"2012","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/22983010","citation_count":42,"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":"34239995","id":"PMC_34239995","title":"Mutations of METTL3 predict response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.","date":"2021","source":"Journal of clinical and translational research","url":"https://pubmed.ncbi.nlm.nih.gov/34239995","citation_count":8,"is_preprint":false},{"pmid":"37895049","id":"PMC_37895049","title":"A Comprehensive Genetic Study of Microtubule-Associated Gene Clusters for Male Infertility in a Taiwanese Cohort.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37895049","citation_count":5,"is_preprint":false},{"pmid":"40089458","id":"PMC_40089458","title":"Core N-DRC components play a crucial role in embryonic development and postnatal organ development.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40089458","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":"40783914","id":"PMC_40783914","title":"[Immunological mechanism of non-obstructive azoospermia: An exploration based on bioinformatics and machine learning].","date":"2024","source":"Zhonghua nan ke xue = National journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/40783914","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7789,"output_tokens":1640,"usd":0.023984,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8322,"output_tokens":2307,"usd":0.049642,"stage2_stop_reason":"end_turn"},"total_usd":0.073626,"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\": 2011,\n      \"finding\": \"CG34110/Ccdc135/FAP50 (DRC7 ortholog) localizes along the sperm flagellum in Drosophila and is tightly associated with outer doublet microtubules of the axoneme; it does not appear to be a component of the central pair, radial spokes, dynein arms, or structures defined by mbo waveform mutants. Loss-of-function of the Drosophila ortholog (lobo mutation) specifically impairs sperm movement into the female storage receptacle, and genetic analyses place it in the same pathway as Pkd2 (polycystin-2 calcium channel).\",\n      \"method\": \"Genetic screen (EMS mutagenesis), loss-of-function phenotypic analysis, subcellular localization by immunofluorescence, axonemal fractionation/biochemical association studies in Chlamydomonas (FAP50)\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by fractionation and immunofluorescence plus genetic epistasis with Pkd2 in a single lab, but ortholog-based (Drosophila/Chlamydomonas), not direct study of mammalian DRC7\",\n      \"pmids\": [\"21289096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DRC7 is required for correct assembly of the Nexin-Dynein Regulatory Complex (N-DRC) and for flagellum formation in mice. Drc7 knockout males are infertile due to short, immotile spermatozoa. In Drc7 KO spermatids, the axoneme is disorganized and the '9+2' microtubule arrangement is disrupted. Critically, other N-DRC components fail to incorporate into the flagellum in the absence of DRC7, establishing DRC7 as essential for N-DRC assembly.\",\n      \"method\": \"Knockout mouse model (Drc7 KO), transmission electron microscopy of axoneme ultrastructure, immunofluorescence of N-DRC components in flagella of KO vs. WT spermatids\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with defined ultrastructural and assembly phenotype, multiple N-DRC components assessed, replicated across multiple analyses in a single rigorous study\",\n      \"pmids\": [\"31961863\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DRC7 interacts with TCTE1 (DRC5) and FBXL13 (DRC6) within the N-DRC; FBXL13 knockout mice show no obvious phenotype, indicating FBXL13 is dispensable, whereas DRC7 is essential, placing DRC7 as a core structural component of the N-DRC required for flagellar axoneme integrity.\",\n      \"method\": \"Knockout mouse models (Fbxl13 KO and Drc7 KO), phenotypic comparison, previously reported protein interaction data cited in the paper\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via KO comparison establishes DRC7 as essential and FBXL13 as dispensable; interaction with TCTE1/FBXL13 is cited from prior work rather than demonstrated here directly\",\n      \"pmids\": [\"31961863\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In Tcte1 (Drc5) knockout mice, DRC7 protein (along with other N-DRC components Fbxl13/DRC6 and Eps8l1/DRC3) fails to be transported to the sperm flagella, demonstrating that DRC5/TCTE1 is required upstream of DRC7 for proper N-DRC assembly and localization in the flagellum.\",\n      \"method\": \"Immunofluorescence in situ staining of N-DRC proteins (including DRC7) in spermatozoa from Tcte1 KO vs. WT mice\",\n      \"journal\": \"Human reproduction open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct immunofluorescence localization experiment with clear loss-of-function readout in a single lab study; establishes epistatic relationship between DRC5 and DRC7 localization\",\n      \"pmids\": [\"38650655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Drc7 knockout mice on a purebred genetic background show that DRC7 is crucial for survival and, in mixed-background mice, for the motility of ependymal cilia, respiratory cilia, and the stability of sperm flagellar axonemes. DRC7 is identified as a core N-DRC component required for N-DRC assembly, consistent with prior findings. Additionally, in the context of N-DRC defects, AKAP3 was found to play a novel role in regulating sperm phosphorylation.\",\n      \"method\": \"Drc7 knockout mice (alongside Drc1-4 KOs), motility assays of cilia/flagella, axoneme ultrastructure analysis\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic KO study with defined phenotypic readouts across multiple ciliated tissues; single lab, replicates and extends prior DRC7 KO findings\",\n      \"pmids\": [\"40089458\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DRC7 (CCDC135/FAP50/CFAP50) is a core structural component of the Nexin-Dynein Regulatory Complex (N-DRC) that associates with outer doublet microtubules of the axoneme; it is required for N-DRC assembly (other N-DRC subunits fail to incorporate into flagella without it), for the stability of the 9+2 axonemal microtubule arrangement in sperm, and for motility of sperm flagella and airway/ependymal cilia, with its own flagellar localization depending on upstream DRC5/TCTE1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DRC7 (CCDC135/FAP50/CFAP50) is a core structural subunit of the Nexin-Dynein Regulatory Complex (N-DRC) that associates with the outer doublet microtubules of the motile axoneme and is essential for ciliary and flagellar motility [#0, #1]. It serves as an organizing component of the N-DRC: in its absence other N-DRC subunits fail to incorporate into the flagellum, and the 9+2 axonemal microtubule arrangement becomes disorganized, producing short, immotile sperm and male infertility in knockout mice [#1]. Within the complex DRC7 functions alongside TCTE1 (DRC5) and FBXL13 (DRC6), and unlike the dispensable FBXL13, DRC7 is required for axonemal integrity; its own flagellar delivery depends on DRC5/TCTE1 acting upstream [#2, #3]. Beyond sperm, DRC7 is required for the motility of ependymal and respiratory cilia and for organismal survival on a purebred background, establishing a broad role across motile ciliated tissues [#4]. The molecular basis by which DRC7 nucleates N-DRC assembly and contacts individual subunits has not been structurally characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established that the DRC7 ortholog is an axonemal protein physically tied to outer doublet microtubules and required for sperm motility, distinguishing it from central pair, radial spoke, and dynein arm structures.\",\n      \"evidence\": \"EMS genetic screen, immunofluorescence localization, and axonemal fractionation in Drosophila and Chlamydomonas orthologs (FAP50), with genetic epistasis to Pkd2\",\n      \"pmids\": [\"21289096\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ortholog-based, not direct study of mammalian DRC7\", \"Molecular function within the axoneme undefined\", \"Mechanistic link to Pkd2 calcium signaling not resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated in mammals that DRC7 is essential for N-DRC assembly itself, since other N-DRC subunits fail to incorporate into the flagellum without it, explaining the disrupted 9+2 axoneme and infertility phenotype.\",\n      \"evidence\": \"Drc7 knockout mouse, transmission electron microscopy of axoneme ultrastructure, immunofluorescence of N-DRC components in KO vs WT spermatids\",\n      \"pmids\": [\"31961863\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding interfaces between DRC7 and other subunits not mapped\", \"No structural model of DRC7 within the N-DRC\", \"Whether assembly defect is nucleation vs stabilization unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placed DRC7 as a core, indispensable subunit relative to other N-DRC members by showing FBXL13 (DRC6) is dispensable while DRC7 is essential, and situating DRC7's interactions with TCTE1 and FBXL13.\",\n      \"evidence\": \"Comparative phenotyping of Fbxl13 KO and Drc7 KO mice; interaction with TCTE1/FBXL13 cited from prior work\",\n      \"pmids\": [\"31961863\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct DRC7-TCTE1/FBXL13 interactions cited rather than demonstrated here\", \"Stoichiometry within the complex unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolved the order of N-DRC assembly by showing DRC5/TCTE1 acts upstream of DRC7, controlling its transport into the flagellum.\",\n      \"evidence\": \"In situ immunofluorescence of N-DRC proteins including DRC7 in Tcte1 KO vs WT spermatozoa\",\n      \"pmids\": [\"38650655\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of DRC7 transport/recruitment not defined\", \"Single-lab localization readout\", \"Whether dependence is direct or indirect unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended DRC7's role beyond sperm to motile cilia generally, showing it is required for ependymal and respiratory ciliary motility, axoneme stability, and survival, with phosphoregulatory consequences via AKAP3.\",\n      \"evidence\": \"Drc7 knockout mice on purebred and mixed backgrounds, motility assays across ciliated tissues, axoneme ultrastructure analysis\",\n      \"pmids\": [\"40089458\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Role of AKAP3 phosphoregulation in N-DRC defects not fully mechanistic\", \"Cause of lethality on purebred background unspecified\", \"Tissue-specific requirements not dissected\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DRC7 structurally nucleates the N-DRC and physically engages each subunit, and the molecular basis of its dependence on DRC5/TCTE1 for flagellar delivery, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution structure of DRC7 in the N-DRC\", \"Direct binding partners not biochemically mapped in mammals\", \"Transport machinery delivering DRC7 to the axoneme unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005930\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"complexes\": [\"Nexin-Dynein Regulatory Complex (N-DRC)\", \"axoneme\"],\n    \"partners\": [\"TCTE1\", \"FBXL13\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}