{"gene":"TEKT1","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2000,"finding":"Mouse Tekt1 protein localizes transiently to the centrosome in round spermatids (co-localizing with the ANA centrosome marker), then extends to the caudal end of elongating spermatids before disappearing, indicating a role in nucleating the flagellar axoneme/basal body during spermiogenesis.","method":"In situ hybridization (temporal RNA expression) and immunofluorescence microscopy with anti-Tekt1 and anti-ANA antibodies in mouse testis sections","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with co-localization to centrosome, single lab, two orthogonal methods (ISH + IF), functional inference from localization pattern","pmids":["11089920"],"is_preprint":false},{"year":2018,"finding":"TEKT1 (tektin-1) localizes to the centrosome in cycling cells, to basal bodies of both primary and motile cilia, and along the axoneme of motile cilia in airway cells; patient-derived biallelic TEKT1 mutations impaired these localizations and caused severe motile cilia motility defects without major ultrastructural changes; knockdown of tekt1 in zebrafish produced phenotypes consistent with defective ciliary motility, confirmed by live imaging; genetic interaction with WDR19 (IFT-A subunit) was demonstrated, with synergistic phenotypic effects.","method":"Immunofluorescence localization in patient airway cells and cycling cells; tekt1 morpholino knockdown in zebrafish with live imaging of ciliary motility; genetic epistasis (tekt1/wdr19 double knockdown in zebrafish); patient-derived biallelic mutation analysis","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (immunolocalization, loss-of-function in two systems, epistasis), functional consequence (motility defect) directly tied to localization, patient mutations corroborated by zebrafish model","pmids":["29121203"],"is_preprint":false},{"year":2022,"finding":"miR-199-5p directly targets the 3′ UTR of Tekt1 mRNA (validated by luciferase reporter assay); elevated miR-199-5p inhibits Tekt1 expression and causes sperm flagellar assembly defects and spermatid apoptosis in vivo, demonstrating that Tekt1 is required for sperm flagella formation during spermiogenesis.","method":"Luciferase reporter assay for direct miR-199-5p/Tekt1 3′UTR interaction; qRT-PCR for expression; intraperitoneal injection of miR-199-5p antagomir/agomir in diploid crucian carp for in vivo functional validation","journal":"Journal of animal science and biotechnology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct target validation by luciferase assay plus in vivo gain/loss-of-function, single lab, orthologous fish model","pmids":["35418106"],"is_preprint":false},{"year":2024,"finding":"TBC1D21 physically interacts with TEKT1 (identified by proteomic analysis of Tbc1d21-null sperm and confirmed by co-immunoprecipitation); loss of TBC1D21 causes abnormal accumulation of TEKT1 in the sperm midpiece region accompanied by disrupted axonemal structures, indicating TBC1D21 modulates TEKT1 protein localization within the axonemal transport system during sperm tail formation.","method":"Comparative sperm proteomics (wild-type vs. Tbc1d21-null mice); co-immunoprecipitation (TBC1D21–TEKT1 interaction); co-localization of TEKT1 with RAB10 by immunofluorescence; Tbc1d21-null mouse model with ultrastructural analysis","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus proteomics plus KO mouse, single lab, two orthogonal methods","pmids":["38822685"],"is_preprint":false},{"year":2026,"finding":"Germline knockout of Tekt1 in mice causes male infertility characterized by impaired sperm motility and loss of the tektin bundle within the doublet microtubule (DMT) of the flagella; TEKT1 is shared by sperm flagella and motile cilia, and its loss phenocopies a specific subtype of asthenozoospermia, demonstrating it is required for flagellar structural integrity and motility.","method":"Tekt1 gene-knockout mice generated from high-resolution DMT structural targeting; fertility assays; sperm motility analysis; structural analysis of tektin bundle; phosphoproteomics; comparison with Tekt5-KO (which is fertile), establishing functional divergence within the tektin family","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — clean KO mouse with defined infertility phenotype, ultrastructural analysis of tektin bundle loss, replicated in context of multiple KO comparisons with orthogonal methods","pmids":["41764189"],"is_preprint":false},{"year":2023,"finding":"TEKT1-expressing cells during spontaneous differentiation of cynomolgus monkey ES cells are multiciliated epithelial-like cells (not germ cells), forming a leash-like structure at the embryoid body periphery with 9+2 axonemal microtubule structures and motile cilia; TEKT1 is expressed in these multiciliated cells alongside TEKT2–5.","method":"TEKT1-promoter::Venus reporter ES cell line in cynomolgus monkey; live fluorescence imaging of EB differentiation; immunofluorescence and transmission electron microscopy for 9+2 axoneme; expression analysis of cilia markers","journal":"Genes to cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter gene directly driven by TEKT1 promoter, TEM structural validation, single lab with multiple orthogonal methods","pmids":["37186436"],"is_preprint":false},{"year":2025,"finding":"TEKT1 binds AMPK-γ (detected by co-immunoprecipitation) and its overexpression in endometrial cancer cells promotes proliferation, migration, and invasion while inhibiting apoptosis; knockdown reverses these effects; the TEKT1–AMPK-γ interaction is proposed to promote fatty acid synthesis via ACC and FASN downregulation.","method":"Co-immunoprecipitation and Western blot (TEKT1–AMPK-γ interaction); cell proliferation, clone formation, migration, invasion, cell cycle, and apoptosis assays with TEKT1 knockdown/overexpression in endometrial cancer cells","journal":"Taiwanese journal of obstetrics & gynecology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP for binding partner, cellular phenotype established but pathway placement (AMPK-γ/ACC/FASN) is not fully validated beyond binding; single lab, no mutagenesis or in vitro reconstitution","pmids":["39794059"],"is_preprint":false}],"current_model":"TEKT1 (tektin-1) is a filament-forming microtubule-stabilizing protein that assembles into the tektin bundle within doublet microtubules of sperm flagella and motile cilia; it transiently associates with the centrosome/basal body during spermiogenesis to nucleate the flagellar axoneme, is required for ciliary motility (loss causing primary ciliary dyskinesia-like defects and male infertility with asthenozoospermia), interacts physically with TBC1D21 (which regulates its axonemal localization), and is post-transcriptionally repressed by miR-199-5p to control sperm flagella assembly."},"narrative":{"mechanistic_narrative":"TEKT1 (tektin-1) is a filament-forming structural protein of the tektin bundle within the doublet microtubules of sperm flagella and motile cilia, where it is required for axonemal structural integrity and ciliary/flagellar motility [PMID:41764189, PMID:29121203]. During spermiogenesis it localizes transiently to the centrosome of round spermatids and then extends to the caudal end of elongating spermatids, consistent with a role in nucleating and building the flagellar axoneme [PMID:11089920], and in cycling cells and airway epithelium it marks centrosomes, basal bodies of primary and motile cilia, and the motile-cilium axoneme [PMID:29121203]. Loss of function establishes its structural role: germline Tekt1 knockout in mice abolishes the tektin bundle within the doublet microtubule and causes asthenozoospermia-like male infertility, a phenotype not shared by Tekt5 knockout and thus reflecting functional divergence within the tektin family [PMID:41764189], while biallelic patient mutations impair its ciliary localization and produce severe motile-cilia motility defects, with a genetic interaction with the IFT-A subunit WDR19 [PMID:29121203]. Its abundance and localization are controlled at two levels: post-transcriptional repression by miR-199-5p, which directly targets the Tekt1 3′UTR to restrain flagellar assembly [PMID:35418106], and physical interaction with TBC1D21, whose loss causes aberrant TEKT1 accumulation in the sperm midpiece, implicating TBC1D21 in directing TEKT1 within the axonemal transport system [PMID:38822685].","teleology":[{"year":2000,"claim":"Established when and where TEKT1 acts during sperm tail formation, linking it to early axoneme/basal body assembly rather than to a mature flagellar component alone.","evidence":"In situ hybridization and immunofluorescence with anti-Tekt1 and anti-centrosome (ANA) antibodies in mouse testis sections","pmids":["11089920"],"confidence":"Medium","gaps":["Localization pattern alone does not demonstrate a nucleation function","No loss-of-function test of the proposed axoneme-nucleating role in this study"]},{"year":2018,"claim":"Extended TEKT1 beyond sperm to motile and primary cilia and tied human disease mutations to ciliary motility defects, defining it as a broadly required ciliary protein.","evidence":"Immunolocalization in patient airway and cycling cells, biallelic mutation analysis, zebrafish tekt1 morpholino knockdown with live ciliary-motility imaging, and tekt1/wdr19 genetic epistasis","pmids":["29121203"],"confidence":"High","gaps":["Mechanism of the WDR19/IFT-A genetic interaction not resolved at the molecular level","No ultrastructural defect identified despite motility loss"]},{"year":2022,"claim":"Identified a post-transcriptional control circuit, showing TEKT1 levels are tuned by miR-199-5p and that this dosage matters for flagellar assembly.","evidence":"Luciferase reporter validation of direct miR-199-5p/Tekt1 3′UTR targeting plus in vivo antagomir/agomir manipulation in diploid crucian carp","pmids":["35418106"],"confidence":"Medium","gaps":["Performed in fish model; conservation of regulation in mammals not shown","Apoptosis phenotype may be indirect rather than a direct TEKT1 function"]},{"year":2024,"claim":"Provided a physical regulator of TEKT1 localization, showing TBC1D21 binds TEKT1 and controls its proper axonemal deposition during tail formation.","evidence":"Comparative sperm proteomics and reciprocal co-immunoprecipitation in Tbc1d21-null mice, with TEKT1/RAB10 co-localization and ultrastructural analysis","pmids":["38822685"],"confidence":"Medium","gaps":["Direct vs. indirect nature of the TBC1D21–TEKT1 interaction not dissected by mapping","Role of RAB10/transport machinery in TEKT1 delivery inferred from co-localization"]},{"year":2026,"claim":"Definitively assigned TEKT1 a structural role as a tektin-bundle component required for doublet-microtubule integrity and motility, distinguishing it functionally from paralog TEKT5.","evidence":"Germline Tekt1-knockout mice with fertility and sperm-motility assays, structural analysis of the tektin bundle, phosphoproteomics, and comparison with fertile Tekt5-KO","pmids":["41764189"],"confidence":"High","gaps":["Molecular basis of functional divergence from other tektins not defined","How tektin-bundle loss mechanistically impairs motility not fully resolved"]},{"year":2025,"claim":"Raised a candidate non-ciliary, cancer-associated function via an AMPK-γ interaction, though this remains the least-substantiated activity.","evidence":"Single co-immunoprecipitation plus proliferation/migration/invasion/apoptosis assays with TEKT1 knockdown/overexpression in endometrial cancer cells","pmids":["39794059"],"confidence":"Low","gaps":["Single Co-IP without reciprocal validation or interaction mapping","AMPK-γ/ACC/FASN pathway placement not validated by mutagenesis or reconstitution","Relationship to the established ciliary/flagellar structural role unclear"]},{"year":null,"claim":"How TEKT1 filaments assemble into and stabilize the tektin bundle within doublet microtubules, and what governs its switch between centrosome/basal-body association and axonemal incorporation, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No high-resolution structure of TEKT1 within the assembled tektin bundle reported in the corpus","Recruitment/handoff mechanism from basal body to axoneme not defined","Whether the cancer-associated AMPK-γ activity is mechanistically distinct from the structural role is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[4,1]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,5]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[4,1]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,4]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[4,0]}],"complexes":["tektin bundle"],"partners":["TBC1D21","WDR19","RAB10","PRKAG (AMPK-Γ)"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q969V4","full_name":"Tektin-1","aliases":[],"length_aa":418,"mass_kda":48.3,"function":"Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules","subcellular_location":"Cytoplasm, cytoskeleton, cilium axoneme; Cytoplasm, cytoskeleton, flagellum axoneme","url":"https://www.uniprot.org/uniprotkb/Q969V4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TEKT1","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/TEKT1","total_profiled":1310},"omim":[{"mim_id":"612683","title":"TEKTIN 3; TEKT3","url":"https://www.omim.org/entry/612683"},{"mim_id":"609002","title":"TEKTIN 1; TEKT1","url":"https://www.omim.org/entry/609002"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"choroid plexus","ntpm":41.7},{"tissue":"fallopian tube","ntpm":47.4}],"url":"https://www.proteinatlas.org/search/TEKT1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q969V4","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q969V4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q969V4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q969V4-F1-predicted_aligned_error_v6.png","plddt_mean":92.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TEKT1","jax_strain_url":"https://www.jax.org/strain/search?query=TEKT1"},"sequence":{"accession":"Q969V4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q969V4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q969V4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q969V4"}},"corpus_meta":[{"pmid":"14962983","id":"PMC_14962983","title":"Spontaneous 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and immunofluorescence microscopy with anti-Tekt1 and anti-ANA antibodies in mouse testis sections\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with co-localization to centrosome, single lab, two orthogonal methods (ISH + IF), functional inference from localization pattern\",\n      \"pmids\": [\"11089920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TEKT1 (tektin-1) localizes to the centrosome in cycling cells, to basal bodies of both primary and motile cilia, and along the axoneme of motile cilia in airway cells; patient-derived biallelic TEKT1 mutations impaired these localizations and caused severe motile cilia motility defects without major ultrastructural changes; knockdown of tekt1 in zebrafish produced phenotypes consistent with defective ciliary motility, confirmed by live imaging; genetic interaction with WDR19 (IFT-A subunit) was demonstrated, with synergistic phenotypic effects.\",\n      \"method\": \"Immunofluorescence localization in patient airway cells and cycling cells; tekt1 morpholino knockdown in zebrafish with live imaging of ciliary motility; genetic epistasis (tekt1/wdr19 double knockdown in zebrafish); patient-derived biallelic mutation analysis\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (immunolocalization, loss-of-function in two systems, epistasis), functional consequence (motility defect) directly tied to localization, patient mutations corroborated by zebrafish model\",\n      \"pmids\": [\"29121203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-199-5p directly targets the 3′ UTR of Tekt1 mRNA (validated by luciferase reporter assay); elevated miR-199-5p inhibits Tekt1 expression and causes sperm flagellar assembly defects and spermatid apoptosis in vivo, demonstrating that Tekt1 is required for sperm flagella formation during spermiogenesis.\",\n      \"method\": \"Luciferase reporter assay for direct miR-199-5p/Tekt1 3′UTR interaction; qRT-PCR for expression; intraperitoneal injection of miR-199-5p antagomir/agomir in diploid crucian carp for in vivo functional validation\",\n      \"journal\": \"Journal of animal science and biotechnology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct target validation by luciferase assay plus in vivo gain/loss-of-function, single lab, orthologous fish model\",\n      \"pmids\": [\"35418106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TBC1D21 physically interacts with TEKT1 (identified by proteomic analysis of Tbc1d21-null sperm and confirmed by co-immunoprecipitation); loss of TBC1D21 causes abnormal accumulation of TEKT1 in the sperm midpiece region accompanied by disrupted axonemal structures, indicating TBC1D21 modulates TEKT1 protein localization within the axonemal transport system during sperm tail formation.\",\n      \"method\": \"Comparative sperm proteomics (wild-type vs. Tbc1d21-null mice); co-immunoprecipitation (TBC1D21–TEKT1 interaction); co-localization of TEKT1 with RAB10 by immunofluorescence; Tbc1d21-null mouse model with ultrastructural analysis\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus proteomics plus KO mouse, single lab, two orthogonal methods\",\n      \"pmids\": [\"38822685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Germline knockout of Tekt1 in mice causes male infertility characterized by impaired sperm motility and loss of the tektin bundle within the doublet microtubule (DMT) of the flagella; TEKT1 is shared by sperm flagella and motile cilia, and its loss phenocopies a specific subtype of asthenozoospermia, demonstrating it is required for flagellar structural integrity and motility.\",\n      \"method\": \"Tekt1 gene-knockout mice generated from high-resolution DMT structural targeting; fertility assays; sperm motility analysis; structural analysis of tektin bundle; phosphoproteomics; comparison with Tekt5-KO (which is fertile), establishing functional divergence within the tektin family\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — clean KO mouse with defined infertility phenotype, ultrastructural analysis of tektin bundle loss, replicated in context of multiple KO comparisons with orthogonal methods\",\n      \"pmids\": [\"41764189\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TEKT1-expressing cells during spontaneous differentiation of cynomolgus monkey ES cells are multiciliated epithelial-like cells (not germ cells), forming a leash-like structure at the embryoid body periphery with 9+2 axonemal microtubule structures and motile cilia; TEKT1 is expressed in these multiciliated cells alongside TEKT2–5.\",\n      \"method\": \"TEKT1-promoter::Venus reporter ES cell line in cynomolgus monkey; live fluorescence imaging of EB differentiation; immunofluorescence and transmission electron microscopy for 9+2 axoneme; expression analysis of cilia markers\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter gene directly driven by TEKT1 promoter, TEM structural validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"37186436\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEKT1 binds AMPK-γ (detected by co-immunoprecipitation) and its overexpression in endometrial cancer cells promotes proliferation, migration, and invasion while inhibiting apoptosis; knockdown reverses these effects; the TEKT1–AMPK-γ interaction is proposed to promote fatty acid synthesis via ACC and FASN downregulation.\",\n      \"method\": \"Co-immunoprecipitation and Western blot (TEKT1–AMPK-γ interaction); cell proliferation, clone formation, migration, invasion, cell cycle, and apoptosis assays with TEKT1 knockdown/overexpression in endometrial cancer cells\",\n      \"journal\": \"Taiwanese journal of obstetrics & gynecology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP for binding partner, cellular phenotype established but pathway placement (AMPK-γ/ACC/FASN) is not fully validated beyond binding; single lab, no mutagenesis or in vitro reconstitution\",\n      \"pmids\": [\"39794059\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEKT1 (tektin-1) is a filament-forming microtubule-stabilizing protein that assembles into the tektin bundle within doublet microtubules of sperm flagella and motile cilia; it transiently associates with the centrosome/basal body during spermiogenesis to nucleate the flagellar axoneme, is required for ciliary motility (loss causing primary ciliary dyskinesia-like defects and male infertility with asthenozoospermia), interacts physically with TBC1D21 (which regulates its axonemal localization), and is post-transcriptionally repressed by miR-199-5p to control sperm flagella assembly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TEKT1 (tektin-1) is a filament-forming structural protein of the tektin bundle within the doublet microtubules of sperm flagella and motile cilia, where it is required for axonemal structural integrity and ciliary/flagellar motility [#4, #1]. During spermiogenesis it localizes transiently to the centrosome of round spermatids and then extends to the caudal end of elongating spermatids, consistent with a role in nucleating and building the flagellar axoneme [#0], and in cycling cells and airway epithelium it marks centrosomes, basal bodies of primary and motile cilia, and the motile-cilium axoneme [#1]. Loss of function establishes its structural role: germline Tekt1 knockout in mice abolishes the tektin bundle within the doublet microtubule and causes asthenozoospermia-like male infertility, a phenotype not shared by Tekt5 knockout and thus reflecting functional divergence within the tektin family [#4], while biallelic patient mutations impair its ciliary localization and produce severe motile-cilia motility defects, with a genetic interaction with the IFT-A subunit WDR19 [#1]. Its abundance and localization are controlled at two levels: post-transcriptional repression by miR-199-5p, which directly targets the Tekt1 3′UTR to restrain flagellar assembly [#2], and physical interaction with TBC1D21, whose loss causes aberrant TEKT1 accumulation in the sperm midpiece, implicating TBC1D21 in directing TEKT1 within the axonemal transport system [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established when and where TEKT1 acts during sperm tail formation, linking it to early axoneme/basal body assembly rather than to a mature flagellar component alone.\",\n      \"evidence\": \"In situ hybridization and immunofluorescence with anti-Tekt1 and anti-centrosome (ANA) antibodies in mouse testis sections\",\n      \"pmids\": [\"11089920\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization pattern alone does not demonstrate a nucleation function\", \"No loss-of-function test of the proposed axoneme-nucleating role in this study\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended TEKT1 beyond sperm to motile and primary cilia and tied human disease mutations to ciliary motility defects, defining it as a broadly required ciliary protein.\",\n      \"evidence\": \"Immunolocalization in patient airway and cycling cells, biallelic mutation analysis, zebrafish tekt1 morpholino knockdown with live ciliary-motility imaging, and tekt1/wdr19 genetic epistasis\",\n      \"pmids\": [\"29121203\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of the WDR19/IFT-A genetic interaction not resolved at the molecular level\", \"No ultrastructural defect identified despite motility loss\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified a post-transcriptional control circuit, showing TEKT1 levels are tuned by miR-199-5p and that this dosage matters for flagellar assembly.\",\n      \"evidence\": \"Luciferase reporter validation of direct miR-199-5p/Tekt1 3′UTR targeting plus in vivo antagomir/agomir manipulation in diploid crucian carp\",\n      \"pmids\": [\"35418106\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Performed in fish model; conservation of regulation in mammals not shown\", \"Apoptosis phenotype may be indirect rather than a direct TEKT1 function\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided a physical regulator of TEKT1 localization, showing TBC1D21 binds TEKT1 and controls its proper axonemal deposition during tail formation.\",\n      \"evidence\": \"Comparative sperm proteomics and reciprocal co-immunoprecipitation in Tbc1d21-null mice, with TEKT1/RAB10 co-localization and ultrastructural analysis\",\n      \"pmids\": [\"38822685\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. indirect nature of the TBC1D21–TEKT1 interaction not dissected by mapping\", \"Role of RAB10/transport machinery in TEKT1 delivery inferred from co-localization\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Definitively assigned TEKT1 a structural role as a tektin-bundle component required for doublet-microtubule integrity and motility, distinguishing it functionally from paralog TEKT5.\",\n      \"evidence\": \"Germline Tekt1-knockout mice with fertility and sperm-motility assays, structural analysis of the tektin bundle, phosphoproteomics, and comparison with fertile Tekt5-KO\",\n      \"pmids\": [\"41764189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of functional divergence from other tektins not defined\", \"How tektin-bundle loss mechanistically impairs motility not fully resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Raised a candidate non-ciliary, cancer-associated function via an AMPK-γ interaction, though this remains the least-substantiated activity.\",\n      \"evidence\": \"Single co-immunoprecipitation plus proliferation/migration/invasion/apoptosis assays with TEKT1 knockdown/overexpression in endometrial cancer cells\",\n      \"pmids\": [\"39794059\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation or interaction mapping\", \"AMPK-γ/ACC/FASN pathway placement not validated by mutagenesis or reconstitution\", \"Relationship to the established ciliary/flagellar structural role unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TEKT1 filaments assemble into and stabilize the tektin bundle within doublet microtubules, and what governs its switch between centrosome/basal-body association and axonemal incorporation, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution structure of TEKT1 within the assembled tektin bundle reported in the corpus\", \"Recruitment/handoff mechanism from basal body to axoneme not defined\", \"Whether the cancer-associated AMPK-γ activity is mechanistically distinct from the structural role is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [4, 1]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [4, 1]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [4, 0]}\n    ],\n    \"complexes\": [\"tektin bundle\"],\n    \"partners\": [\"TBC1D21\", \"WDR19\", \"RAB10\", \"PRKAG (AMPK-\\u03b3)\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}