{"gene":"TEKT1","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2000,"finding":"Mouse Tekt1 protein is transiently associated with the centrosome in round spermatids, co-localizing with the centrosome marker ANA, and subsequently distributes along elongating spermatid caudal ends before disappearing, indicating a role in nucleation of the flagellar axoneme basal body during spermiogenesis.","method":"In situ hybridization and immunofluorescence microscopy with anti-Tekt1 antibodies and co-localization with anti-ANA (centrosome marker) in mouse testis sections","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization with functional consequence (axoneme nucleation), single lab, two orthogonal methods","pmids":["11089920"],"is_preprint":false},{"year":2018,"finding":"Tektin-1 (TEKT1) localizes to the centrosome in cycling cells, to basal bodies of both primary and motile cilia, and to the axoneme of motile cilia in airway cells; patient-derived biallelic mutations in TEKT1 impaired these localizations and caused severe motility defects in airway cilia without major ultrastructural changes; knockdown of tekt1 in zebrafish confirmed a function in ciliary motility, and genetic interaction with wdr19 was demonstrated by a synergistic phenotype.","method":"Immunofluorescence localization in patient airway cells and cycling cells; zebrafish tekt1 morpholino knockdown with live imaging; patient-derived mutation analysis; genetic epistasis with wdr19","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (localization, functional motility assay, in vivo knockdown, genetic epistasis), moderate evidence","pmids":["29121203"],"is_preprint":false},{"year":2022,"finding":"miR-199-5p directly targets Tekt1 mRNA (validated by luciferase reporter assay) and negatively regulates its expression; elevated miR-199-5p in vivo inhibits sperm flagella formation during spermiogenesis, causing spermatid apoptosis and abnormal spermatozoa structure, demonstrating that Tekt1 is required for sperm flagellar assembly.","method":"Luciferase reporter assay for miR-199-5p/Tekt1 3'UTR interaction; in vivo intraperitoneal injection of miR-199-5p antagomir/agomir in diploid red crucian carp; qRT-PCR expression analysis","journal":"Journal of animal science and biotechnology","confidence":"Medium","confidence_rationale":"Tier 2 — direct target validation by luciferase assay plus in vivo gain/loss-of-function with defined phenotype, single lab","pmids":["35418106"],"is_preprint":false},{"year":2024,"finding":"TBC1D21 physically interacts with TEKT1 (co-immunoprecipitation), and loss of TBC1D21 causes abnormal accumulation of TEKT1 in the midpiece region of sperm tails accompanied by disrupted axonemal structures, indicating that TBC1D21 modulates TEKT1 protein localization in the axonemal transport system during sperm tail formation.","method":"Comparative proteomics of wild-type vs. Tbc1d21-null mouse sperm; co-immunoprecipitation of TBC1D21 and TEKT1; immunofluorescence co-localization of TEKT1 with RAB10 during sperm tail formation","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP plus proteomic and localization data in KO model, single lab","pmids":["38822685"],"is_preprint":false},{"year":2026,"finding":"TEKT1 knockout mice are male-infertile due to impaired sperm motility and loss of the tektin bundle within the doublet microtubule of the sperm flagellum/motile cilia axoneme; TEKT1 is shared by sperm flagella and motile cilia, and its depletion defines a distinct subtype of asthenozoospermia, demonstrating that TEKT1 is an essential structural component of the axonemal tektin filament.","method":"Gene knockout mouse model; sperm motility analysis; high-resolution structural analysis of doublet microtubules; phenotypic comparison with other tektin/enzyme KO mice","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 — clean KO with defined infertility phenotype, structural validation of tektin bundle loss, multiple orthogonal readouts","pmids":["41764189"],"is_preprint":false},{"year":2025,"finding":"TEKT1 binds to the AMPK-γ subunit (co-immunoprecipitation) in endometrial cancer cells and promotes fatty acid synthesis associated with downregulation of ACC and FASN; TEKT1 overexpression promotes proliferation, migration, and invasion while inhibiting apoptosis in endometrial cancer cells.","method":"Co-immunoprecipitation; Western blot; cell proliferation, clone formation, migration, invasion, cycle, and apoptosis assays in endometrial cancer cell lines","journal":"Taiwanese journal of obstetrics & gynecology","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP with cellular phenotype in cancer context, single lab, no mechanistic follow-up","pmids":["39794059"],"is_preprint":false},{"year":2023,"finding":"In spontaneously differentiating cynomolgus monkey ES cells, TEKT1 promoter-driven Venus expression marks multiciliated epithelial-like cells that form leash-like structures bearing motile cilia with 9+2 microtubule architecture, demonstrating that TEKT1 is a marker and component of multiciliated cells—not only sperm—during ES cell differentiation.","method":"Reporter ES cell line (Venus under TEKT1 promoter); live imaging; immunofluorescence for cilia markers; transmission electron microscopy for 9+2 structure","journal":"Genes to cells","confidence":"Medium","confidence_rationale":"Tier 2 — reporter line with structural validation (TEM) and multiple cilia markers, single lab","pmids":["37186436"],"is_preprint":false}],"current_model":"TEKT1 encodes an intermediate filament-like tektin protein that is an essential structural component of the axonemal tektin bundle in sperm flagella and motile cilia; it is transiently associated with the centrosome/basal body during flagellar nucleation, its localization in the axoneme is regulated by TBC1D21-mediated transport, its mRNA is post-transcriptionally regulated by miR-199-5p, and its loss causes male infertility through impaired sperm motility and tektin bundle disassembly, while also being required for motile cilia function in airway epithelial cells."},"narrative":{"teleology":[{"year":2000,"claim":"The first subcellular localization of TEKT1 revealed its transient association with the centrosome of round spermatids, establishing that it participates early in flagellar axoneme nucleation rather than acting solely as a late structural component.","evidence":"Immunofluorescence co-localization with centrosome marker ANA and in situ hybridization in mouse testis sections","pmids":["11089920"],"confidence":"Medium","gaps":["No loss-of-function data to confirm a functional requirement at the centrosome","Mechanism of TEKT1 recruitment to and departure from the centrosome unknown"]},{"year":2018,"claim":"Patient-derived biallelic TEKT1 mutations and zebrafish knockdown demonstrated that TEKT1 is required for motile cilia beat function—not only sperm flagella—and showed genetic interaction with the intraflagellar transport component WDR19, placing TEKT1 in a broader ciliary assembly pathway.","evidence":"Immunofluorescence in patient airway cells and cycling cells; zebrafish tekt1 morpholino knockdown with live motility imaging; genetic epistasis with wdr19","pmids":["29121203"],"confidence":"High","gaps":["Structural basis of motility defect without ultrastructural changes is unexplained","Nature of TEKT1–WDR19 functional relationship (direct or indirect) not resolved"]},{"year":2022,"claim":"Identification of miR-199-5p as a direct post-transcriptional regulator of TEKT1 mRNA revealed that TEKT1 expression levels must be tightly controlled for normal flagellar assembly, as its suppression causes spermatid apoptosis and flagellar defects.","evidence":"Luciferase reporter assay for miR-199-5p/Tekt1 3′UTR; in vivo agomir/antagomir injection in diploid red crucian carp","pmids":["35418106"],"confidence":"Medium","gaps":["Relevance of miR-199-5p regulation to mammalian spermatogenesis not tested","Whether other miRNAs also regulate TEKT1 is unknown"]},{"year":2023,"claim":"TEKT1 promoter-driven reporter expression in primate ES cells marked multiciliated epithelial-like cells bearing 9+2 motile cilia, confirming TEKT1 as a conserved marker of multiciliated cell identity beyond the germline.","evidence":"Venus reporter under TEKT1 promoter in cynomolgus monkey ES cells; transmission electron microscopy confirming 9+2 architecture","pmids":["37186436"],"confidence":"Medium","gaps":["Functional requirement of TEKT1 in ES-derived multiciliated cells not tested by loss-of-function","Whether TEKT1 contributes to multiciliogenesis or is only a late differentiation marker is unclear"]},{"year":2024,"claim":"Physical interaction between TBC1D21 and TEKT1, combined with mislocalization of TEKT1 in Tbc1d21-null sperm, established that axonemal TEKT1 distribution is actively regulated by a Rab-associated transport mechanism during sperm tail assembly.","evidence":"Co-immunoprecipitation; comparative proteomics of WT vs. Tbc1d21-KO mouse sperm; immunofluorescence co-localization with RAB10","pmids":["38822685"],"confidence":"Medium","gaps":["Whether TBC1D21 GAP activity toward a specific Rab is the operative mechanism remains untested","Whether this transport pathway operates in motile cilia of non-sperm cells is unknown"]},{"year":2025,"claim":"A reported interaction between TEKT1 and AMPK-γ in endometrial cancer cells linked TEKT1 to fatty acid synthesis and cancer cell proliferation, but this finding stands outside the established ciliary/flagellar context and lacks mechanistic follow-up.","evidence":"Co-immunoprecipitation and Western blot in endometrial cancer cell lines with overexpression phenotypes","pmids":["39794059"],"confidence":"Low","gaps":["Single Co-IP without reciprocal validation or domain mapping","No evidence TEKT1 is normally expressed in endometrial tissue at physiologically meaningful levels","No in vivo validation of the AMPK interaction"]},{"year":2026,"claim":"TEKT1 knockout mice provided definitive evidence that TEKT1 is an essential structural subunit of the tektin bundle within axonemal doublet microtubules, and its loss defines a distinct asthenozoospermia subtype through complete loss of sperm motility.","evidence":"Gene knockout mouse; sperm motility analysis; high-resolution structural analysis of doublet microtubules","pmids":["41764189"],"confidence":"High","gaps":["Precise position of TEKT1 within the tektin filament relative to TEKT2–5 not resolved at atomic resolution","Whether TEKT1 loss in mice also recapitulates airway cilia dysfunction (as seen in human patients) was not reported"]},{"year":null,"claim":"It remains unknown how TEKT1 is assembled into the tektin bundle at atomic resolution, what specific intraflagellar transport adaptors deliver TEKT1 to its axonemal position, and whether TEKT1 mutations constitute a bona fide primary ciliary dyskinesia locus in humans.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of TEKT1 or the tektin bundle exists","Relationship between TEKT1 and IFT machinery beyond genetic interaction with WDR19 is uncharacterized","Human genetic confirmation of TEKT1 as a primary ciliary dyskinesia gene in larger cohorts is lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,4]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,4,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,4]}],"complexes":["tektin bundle"],"partners":["TBC1D21","WDR19"],"other_free_text":[]},"mechanistic_narrative":"TEKT1 encodes a tektin family protein that serves as an essential structural component of the tektin bundle within doublet microtubules of motile cilia and sperm flagella. TEKT1 is transiently associated with the centrosome/basal body during flagellar nucleation in spermatids and subsequently localizes along the axoneme, where its proper distribution depends on TBC1D21-mediated transport; loss of TBC1D21 causes aberrant TEKT1 accumulation in the sperm midpiece [PMID:11089920, PMID:38822685]. TEKT1 knockout mice are male-infertile due to impaired sperm motility and disassembly of the tektin bundle, and biallelic TEKT1 mutations in humans cause severe motile cilia dysmotility in airway epithelial cells without major ultrastructural defects, establishing that TEKT1 is required for motile ciliary function beyond spermatogenesis [PMID:41764189, PMID:29121203]. TEKT1 mRNA is post-transcriptionally regulated by miR-199-5p, and its suppression disrupts flagellar assembly and causes spermatid apoptosis [PMID:35418106]."},"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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co-localization with anti-ANA (centrosome marker) in mouse testis sections\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization with functional consequence (axoneme nucleation), single lab, two orthogonal methods\",\n      \"pmids\": [\"11089920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Tektin-1 (TEKT1) localizes to the centrosome in cycling cells, to basal bodies of both primary and motile cilia, and to the axoneme of motile cilia in airway cells; patient-derived biallelic mutations in TEKT1 impaired these localizations and caused severe motility defects in airway cilia without major ultrastructural changes; knockdown of tekt1 in zebrafish confirmed a function in ciliary motility, and genetic interaction with wdr19 was demonstrated by a synergistic phenotype.\",\n      \"method\": \"Immunofluorescence localization in patient airway cells and cycling cells; zebrafish tekt1 morpholino knockdown with live imaging; patient-derived mutation analysis; genetic epistasis with wdr19\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (localization, functional motility assay, in vivo knockdown, genetic epistasis), moderate evidence\",\n      \"pmids\": [\"29121203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-199-5p directly targets Tekt1 mRNA (validated by luciferase reporter assay) and negatively regulates its expression; elevated miR-199-5p in vivo inhibits sperm flagella formation during spermiogenesis, causing spermatid apoptosis and abnormal spermatozoa structure, demonstrating that Tekt1 is required for sperm flagellar assembly.\",\n      \"method\": \"Luciferase reporter assay for miR-199-5p/Tekt1 3'UTR interaction; in vivo intraperitoneal injection of miR-199-5p antagomir/agomir in diploid red crucian carp; qRT-PCR expression analysis\",\n      \"journal\": \"Journal of animal science and biotechnology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct target validation by luciferase assay plus in vivo gain/loss-of-function with defined phenotype, single lab\",\n      \"pmids\": [\"35418106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TBC1D21 physically interacts with TEKT1 (co-immunoprecipitation), and loss of TBC1D21 causes abnormal accumulation of TEKT1 in the midpiece region of sperm tails accompanied by disrupted axonemal structures, indicating that TBC1D21 modulates TEKT1 protein localization in the axonemal transport system during sperm tail formation.\",\n      \"method\": \"Comparative proteomics of wild-type vs. Tbc1d21-null mouse sperm; co-immunoprecipitation of TBC1D21 and TEKT1; immunofluorescence co-localization of TEKT1 with RAB10 during sperm tail formation\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus proteomic and localization data in KO model, single lab\",\n      \"pmids\": [\"38822685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TEKT1 knockout mice are male-infertile due to impaired sperm motility and loss of the tektin bundle within the doublet microtubule of the sperm flagellum/motile cilia axoneme; TEKT1 is shared by sperm flagella and motile cilia, and its depletion defines a distinct subtype of asthenozoospermia, demonstrating that TEKT1 is an essential structural component of the axonemal tektin filament.\",\n      \"method\": \"Gene knockout mouse model; sperm motility analysis; high-resolution structural analysis of doublet microtubules; phenotypic comparison with other tektin/enzyme KO mice\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — clean KO with defined infertility phenotype, structural validation of tektin bundle loss, multiple orthogonal readouts\",\n      \"pmids\": [\"41764189\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEKT1 binds to the AMPK-γ subunit (co-immunoprecipitation) in endometrial cancer cells and promotes fatty acid synthesis associated with downregulation of ACC and FASN; TEKT1 overexpression promotes proliferation, migration, and invasion while inhibiting apoptosis in endometrial cancer cells.\",\n      \"method\": \"Co-immunoprecipitation; Western blot; cell proliferation, clone formation, migration, invasion, cycle, and apoptosis assays in endometrial cancer cell lines\",\n      \"journal\": \"Taiwanese journal of obstetrics & gynecology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP with cellular phenotype in cancer context, single lab, no mechanistic follow-up\",\n      \"pmids\": [\"39794059\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In spontaneously differentiating cynomolgus monkey ES cells, TEKT1 promoter-driven Venus expression marks multiciliated epithelial-like cells that form leash-like structures bearing motile cilia with 9+2 microtubule architecture, demonstrating that TEKT1 is a marker and component of multiciliated cells—not only sperm—during ES cell differentiation.\",\n      \"method\": \"Reporter ES cell line (Venus under TEKT1 promoter); live imaging; immunofluorescence for cilia markers; transmission electron microscopy for 9+2 structure\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reporter line with structural validation (TEM) and multiple cilia markers, single lab\",\n      \"pmids\": [\"37186436\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEKT1 encodes an intermediate filament-like tektin protein that is an essential structural component of the axonemal tektin bundle in sperm flagella and motile cilia; it is transiently associated with the centrosome/basal body during flagellar nucleation, its localization in the axoneme is regulated by TBC1D21-mediated transport, its mRNA is post-transcriptionally regulated by miR-199-5p, and its loss causes male infertility through impaired sperm motility and tektin bundle disassembly, while also being required for motile cilia function in airway epithelial cells.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TEKT1 encodes a tektin family protein that serves as an essential structural component of the tektin bundle within doublet microtubules of motile cilia and sperm flagella. TEKT1 is transiently associated with the centrosome/basal body during flagellar nucleation in spermatids and subsequently localizes along the axoneme, where its proper distribution depends on TBC1D21-mediated transport; loss of TBC1D21 causes aberrant TEKT1 accumulation in the sperm midpiece [PMID:11089920, PMID:38822685]. TEKT1 knockout mice are male-infertile due to impaired sperm motility and disassembly of the tektin bundle, and biallelic TEKT1 mutations in humans cause severe motile cilia dysmotility in airway epithelial cells without major ultrastructural defects, establishing that TEKT1 is required for motile ciliary function beyond spermatogenesis [PMID:41764189, PMID:29121203]. TEKT1 mRNA is post-transcriptionally regulated by miR-199-5p, and its suppression disrupts flagellar assembly and causes spermatid apoptosis [PMID:35418106].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"The first subcellular localization of TEKT1 revealed its transient association with the centrosome of round spermatids, establishing that it participates early in flagellar axoneme nucleation rather than acting solely as a late structural component.\",\n      \"evidence\": \"Immunofluorescence co-localization with centrosome marker ANA and in situ hybridization in mouse testis sections\",\n      \"pmids\": [\"11089920\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No loss-of-function data to confirm a functional requirement at the centrosome\",\n        \"Mechanism of TEKT1 recruitment to and departure from the centrosome unknown\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Patient-derived biallelic TEKT1 mutations and zebrafish knockdown demonstrated that TEKT1 is required for motile cilia beat function—not only sperm flagella—and showed genetic interaction with the intraflagellar transport component WDR19, placing TEKT1 in a broader ciliary assembly pathway.\",\n      \"evidence\": \"Immunofluorescence in patient airway cells and cycling cells; zebrafish tekt1 morpholino knockdown with live motility imaging; genetic epistasis with wdr19\",\n      \"pmids\": [\"29121203\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of motility defect without ultrastructural changes is unexplained\",\n        \"Nature of TEKT1–WDR19 functional relationship (direct or indirect) not resolved\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identification of miR-199-5p as a direct post-transcriptional regulator of TEKT1 mRNA revealed that TEKT1 expression levels must be tightly controlled for normal flagellar assembly, as its suppression causes spermatid apoptosis and flagellar defects.\",\n      \"evidence\": \"Luciferase reporter assay for miR-199-5p/Tekt1 3′UTR; in vivo agomir/antagomir injection in diploid red crucian carp\",\n      \"pmids\": [\"35418106\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relevance of miR-199-5p regulation to mammalian spermatogenesis not tested\",\n        \"Whether other miRNAs also regulate TEKT1 is unknown\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"TEKT1 promoter-driven reporter expression in primate ES cells marked multiciliated epithelial-like cells bearing 9+2 motile cilia, confirming TEKT1 as a conserved marker of multiciliated cell identity beyond the germline.\",\n      \"evidence\": \"Venus reporter under TEKT1 promoter in cynomolgus monkey ES cells; transmission electron microscopy confirming 9+2 architecture\",\n      \"pmids\": [\"37186436\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional requirement of TEKT1 in ES-derived multiciliated cells not tested by loss-of-function\",\n        \"Whether TEKT1 contributes to multiciliogenesis or is only a late differentiation marker is unclear\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Physical interaction between TBC1D21 and TEKT1, combined with mislocalization of TEKT1 in Tbc1d21-null sperm, established that axonemal TEKT1 distribution is actively regulated by a Rab-associated transport mechanism during sperm tail assembly.\",\n      \"evidence\": \"Co-immunoprecipitation; comparative proteomics of WT vs. Tbc1d21-KO mouse sperm; immunofluorescence co-localization with RAB10\",\n      \"pmids\": [\"38822685\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether TBC1D21 GAP activity toward a specific Rab is the operative mechanism remains untested\",\n        \"Whether this transport pathway operates in motile cilia of non-sperm cells is unknown\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A reported interaction between TEKT1 and AMPK-γ in endometrial cancer cells linked TEKT1 to fatty acid synthesis and cancer cell proliferation, but this finding stands outside the established ciliary/flagellar context and lacks mechanistic follow-up.\",\n      \"evidence\": \"Co-immunoprecipitation and Western blot in endometrial cancer cell lines with overexpression phenotypes\",\n      \"pmids\": [\"39794059\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation or domain mapping\",\n        \"No evidence TEKT1 is normally expressed in endometrial tissue at physiologically meaningful levels\",\n        \"No in vivo validation of the AMPK interaction\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"TEKT1 knockout mice provided definitive evidence that TEKT1 is an essential structural subunit of the tektin bundle within axonemal doublet microtubules, and its loss defines a distinct asthenozoospermia subtype through complete loss of sperm motility.\",\n      \"evidence\": \"Gene knockout mouse; sperm motility analysis; high-resolution structural analysis of doublet microtubules\",\n      \"pmids\": [\"41764189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise position of TEKT1 within the tektin filament relative to TEKT2–5 not resolved at atomic resolution\",\n        \"Whether TEKT1 loss in mice also recapitulates airway cilia dysfunction (as seen in human patients) was not reported\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how TEKT1 is assembled into the tektin bundle at atomic resolution, what specific intraflagellar transport adaptors deliver TEKT1 to its axonemal position, and whether TEKT1 mutations constitute a bona fide primary ciliary dyskinesia locus in humans.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of TEKT1 or the tektin bundle exists\",\n        \"Relationship between TEKT1 and IFT machinery beyond genetic interaction with WDR19 is uncharacterized\",\n        \"Human genetic confirmation of TEKT1 as a primary ciliary dyskinesia gene in larger cohorts is lacking\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 4, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"complexes\": [\n      \"tektin bundle\"\n    ],\n    \"partners\": [\n      \"TBC1D21\",\n      \"WDR19\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}