{"gene":"TEDC2","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2025,"finding":"TEDC2 physically interacts with delta-tubulin, epsilon-tubulin, and TEDC1 to form a tetrameric complex required for centriole architecture; TEDC1 and TEDC2 form a subcomplex in the absence of the tubulins, consistent with an AlphaFold Multimer model of the tetramer.","method":"Co-immunoprecipitation, ultrastructure expansion microscopy, genetic knockout, AlphaFold Multimer structural modeling","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP/physical interaction, structural model, and multiple orthogonal methods in a single rigorous study","pmids":["40067174"],"is_preprint":false},{"year":2025,"finding":"Cells lacking TEDC2 form abnormal centrioles characterized by absence of triplet microtubules, lack of central core scaffold proteins (e.g., POC5), an expanded proximal region, and a futile cycle of centriole elongation, fragmentation, and disintegration during mitosis.","method":"CRISPR/Cas9 knockout, ultrastructure expansion microscopy, immunofluorescence","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined structural/cellular phenotype using multiple imaging modalities","pmids":["40067174"],"is_preprint":false},{"year":2025,"finding":"TEDC2 localizes to centrosomes and its centrosomal localization is mutually dependent on TEDC1 and on delta-tubulin and epsilon-tubulin.","method":"Immunofluorescence localization in CRISPR knockout cell lines","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — direct localization experiment with functional epistasis across multiple KO lines","pmids":["40067174"],"is_preprint":false},{"year":2025,"finding":"A C-terminally truncated TEDC1 protein (produced by a frameshift variant) impairs binding with TEDC2, demonstrating that the TEDC1 C-terminus is required for the TEDC1–TEDC2 interaction.","method":"Patient-derived cell analysis, in vitro binding assay, exome sequencing","journal":"European journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 — natural loss-of-function variant with defined binding defect, single study","pmids":["39979680"],"is_preprint":false},{"year":2025,"finding":"Knockdown of TEDC2 inhibited proliferation, migration, and cancer stem cell maintenance in non-small cell lung cancer cells primarily through inhibition of the Hedgehog signaling pathway, and enhanced sensitivity to cisplatin in vitro and in vivo.","method":"siRNA/shRNA knockdown, functional assays (proliferation, migration, sphere formation), in vivo xenograft, pathway reporter assays","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 3 — KD with defined phenotype and pathway placement, single lab, no direct biochemical interaction shown","pmids":["41352505"],"is_preprint":false},{"year":2024,"finding":"Knockdown of TEDC2 in lung adenocarcinoma cell lines slowed proliferation, migration, and invasion efficiency.","method":"siRNA knockdown, CCK8 proliferation assay, transwell migration/invasion assay","journal":"PeerJ","confidence":"Low","confidence_rationale":"Tier 3 — single lab, phenotypic KD data without pathway mechanism","pmids":["39553728"],"is_preprint":false},{"year":2023,"finding":"Overexpression of TEDC2 promoted cell metastasis and proliferation in hepatocellular carcinoma cell lines in vitro, and TP53 mutations were found to regulate TEDC2 expression.","method":"Overexpression in HCC cell lines, proliferation and migration assays, bioinformatic correlation of TP53 mutation status with TEDC2 expression","journal":"Digestive and liver disease","confidence":"Low","confidence_rationale":"Tier 3 — single lab, in vitro overexpression phenotype; TP53-TEDC2 link is bioinformatic only","pmids":["37867019"],"is_preprint":false}],"current_model":"TEDC2 forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin at centrosomes; this complex is essential for centriole triplet microtubule architecture and structural integrity, as loss of any component causes abnormal centrioles that elongate but lack triplet microtubules and central core proteins and subsequently fragment during mitosis."},"narrative":{"teleology":[{"year":2023,"claim":"Initial cancer-cell studies raised the question of whether TEDC2 has a general role in cell proliferation, showing that its overexpression promotes proliferation and migration in hepatocellular carcinoma cells.","evidence":"Overexpression and proliferation/migration assays in HCC cell lines","pmids":["37867019"],"confidence":"Low","gaps":["Single-lab overexpression study without mechanistic pathway identification","TP53–TEDC2 regulatory link is bioinformatic only, not validated experimentally","No biochemical or structural understanding of TEDC2 function"]},{"year":2024,"claim":"Knockdown studies in lung adenocarcinoma cells corroborated that TEDC2 depletion impairs proliferation and migration, but still without identifying the underlying mechanism.","evidence":"siRNA knockdown with CCK8 proliferation and transwell assays in LUAD lines","pmids":["39553728"],"confidence":"Low","gaps":["No pathway mechanism identified","Not independently confirmed outside a single lab","No connection to centriole biology yet established"]},{"year":2025,"claim":"The core biochemical identity of TEDC2 was established: it forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin that localizes to centrosomes and is required for centriole triplet microtubule architecture, with loss causing centriole structural collapse and mitotic fragmentation.","evidence":"Reciprocal co-immunoprecipitation, CRISPR/Cas9 knockout in human cells, ultrastructure expansion microscopy, AlphaFold Multimer modeling","pmids":["40067174"],"confidence":"High","gaps":["How the tetramer is recruited to the centriole and at what stage of centriole biogenesis it acts is unresolved","Stoichiometry and atomic-resolution structure of the endogenous complex have not been determined experimentally","Whether loss of triplet microtubules explains the proliferation defects seen in cancer knockdown studies is untested"]},{"year":2025,"claim":"The TEDC1–TEDC2 interaction interface was defined: a patient-derived TEDC1 C-terminal truncation disrupts binding to TEDC2, demonstrating that the TEDC1 C-terminus is required for subcomplex formation.","evidence":"Patient exome sequencing, in vitro binding assay with truncated TEDC1","pmids":["39979680"],"confidence":"Medium","gaps":["Whether this variant causes a Mendelian ciliopathy phenotype in patients has not been firmly established","Residue-level mapping of the TEDC1–TEDC2 binding interface is lacking"]},{"year":2025,"claim":"A signaling pathway was linked to TEDC2's proliferative role: TEDC2 knockdown in NSCLC cells inhibited Hedgehog signaling, reduced cancer stem cell maintenance, and sensitized cells to cisplatin.","evidence":"siRNA/shRNA knockdown, Hedgehog pathway reporter assays, in vivo xenograft","pmids":["41352505"],"confidence":"Medium","gaps":["Whether the Hedgehog link is a direct consequence of defective centriole/cilium architecture or an independent function is unknown","No direct biochemical interaction between TEDC2 and Hedgehog pathway components has been shown"]},{"year":null,"claim":"Key open questions include how the TEDC1–TEDC2–delta-tubulin–epsilon-tubulin tetramer is recruited to nascent centrioles, whether TEDC2 loss causes ciliopathy in humans, and whether the cancer-cell phenotypes are secondary to centriole/cilium defects.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimental structure of the endogenous tetramer at atomic resolution","Mechanism linking centriole triplet microtubule loss to Hedgehog pathway suppression is unknown","In vivo organismal phenotype of TEDC2 loss in mammals has not been reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1]}],"complexes":["TEDC1–TEDC2–delta-tubulin–epsilon-tubulin tetramer"],"partners":["TEDC1","TUBD1","TUBE1"],"other_free_text":[]},"mechanistic_narrative":"TEDC2 is a centrosomal protein that forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin, and this complex is essential for building and maintaining centriole triplet microtubule architecture [PMID:40067174]. Within the complex, TEDC1 and TEDC2 form a subcomplex whose assembly requires the TEDC1 C-terminus, and centrosomal localization of TEDC2 is mutually dependent on TEDC1, delta-tubulin, and epsilon-tubulin [PMID:40067174, PMID:39979680]. Loss of TEDC2 produces centrioles that lack triplet microtubules and central core scaffold proteins (e.g., POC5), exhibit an expanded proximal region, and undergo a futile cycle of elongation, fragmentation, and disintegration during mitosis [PMID:40067174]. TEDC2 knockdown in non-small cell lung cancer cells inhibits Hedgehog signaling and reduces proliferation and cancer stem cell maintenance [PMID:41352505]."},"prefetch_data":{"uniprot":{"accession":"Q7L2K0","full_name":"Tubulin epsilon and delta complex protein 2","aliases":[],"length_aa":433,"mass_kda":46.4,"function":"Acts as a positive regulator of ciliary hedgehog signaling. Required for centriole stability","subcellular_location":"Cell projection, cilium; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","url":"https://www.uniprot.org/uniprotkb/Q7L2K0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TEDC2","classification":"Not Classified","n_dependent_lines":468,"n_total_lines":1208,"dependency_fraction":0.38741721854304634},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TEDC2","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cell Junctions","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"bone marrow","ntpm":3.8},{"tissue":"testis","ntpm":4.9}],"url":"https://www.proteinatlas.org/search/TEDC2"},"hgnc":{"alias_symbol":["FLJ13909"],"prev_symbol":["C16orf59"]},"alphafold":{"accession":"Q7L2K0","domains":[{"cath_id":"1.10.287","chopping":"262-326","consensus_level":"medium","plddt":89.1717,"start":262,"end":326}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7L2K0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7L2K0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7L2K0-F1-predicted_aligned_error_v6.png","plddt_mean":67.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TEDC2","jax_strain_url":"https://www.jax.org/strain/search?query=TEDC2"},"sequence":{"accession":"Q7L2K0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7L2K0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7L2K0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7L2K0"}},"corpus_meta":[{"pmid":"26019538","id":"PMC_26019538","title":"Whole genome methylation analyses of schizophrenia patients before and after treatment.","date":"2014","source":"Biotechnology, biotechnological equipment","url":"https://pubmed.ncbi.nlm.nih.gov/26019538","citation_count":32,"is_preprint":false},{"pmid":"26026093","id":"PMC_26026093","title":"Microarray Gene-expression Profiling Analysis Comparing PCNSL and Non-CNS Diffuse Large B-Cell Lymphoma.","date":"2015","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/26026093","citation_count":16,"is_preprint":false},{"pmid":"26356813","id":"PMC_26356813","title":"Triple-layer dissection of the lung adenocarcinoma transcriptome: regulation at the gene, transcript, and exon levels.","date":"2015","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/26356813","citation_count":15,"is_preprint":false},{"pmid":"33993705","id":"PMC_33993705","title":"Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study.","date":"2021","source":"Epigenomics","url":"https://pubmed.ncbi.nlm.nih.gov/33993705","citation_count":8,"is_preprint":false},{"pmid":"40067174","id":"PMC_40067174","title":"A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture.","date":"2025","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/40067174","citation_count":6,"is_preprint":false},{"pmid":"37867019","id":"PMC_37867019","title":"TEDC2 plays an oncogenic role and serves as a therapeutic target of hepatocellular carcinoma.","date":"2023","source":"Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver","url":"https://pubmed.ncbi.nlm.nih.gov/37867019","citation_count":3,"is_preprint":false},{"pmid":"39979680","id":"PMC_39979680","title":"Biallelic TEDC1 variants cause a new syndrome with severe growth impairment and endocrine complications.","date":"2025","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/39979680","citation_count":2,"is_preprint":false},{"pmid":"39553728","id":"PMC_39553728","title":"Comprehensive analysis of transcriptomics and radiomics revealed the potential of TEDC2 as a diagnostic marker for lung adenocarcinoma.","date":"2024","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/39553728","citation_count":1,"is_preprint":false},{"pmid":"41352505","id":"PMC_41352505","title":"Tubulin epsilon and delta complex 2 enhances malignancy in non-small cell lung cancer by activating the hedgehog signaling pathway to promote tumor cell stemness.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/41352505","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6052,"output_tokens":1385,"usd":0.019466},"stage2":{"model":"claude-opus-4-6","input_tokens":4641,"output_tokens":1677,"usd":0.097695},"total_usd":0.117161,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"TEDC2 physically interacts with delta-tubulin, epsilon-tubulin, and TEDC1 to form a tetrameric complex required for centriole architecture; TEDC1 and TEDC2 form a subcomplex in the absence of the tubulins, consistent with an AlphaFold Multimer model of the tetramer.\",\n      \"method\": \"Co-immunoprecipitation, ultrastructure expansion microscopy, genetic knockout, AlphaFold Multimer structural modeling\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP/physical interaction, structural model, and multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"40067174\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cells lacking TEDC2 form abnormal centrioles characterized by absence of triplet microtubules, lack of central core scaffold proteins (e.g., POC5), an expanded proximal region, and a futile cycle of centriole elongation, fragmentation, and disintegration during mitosis.\",\n      \"method\": \"CRISPR/Cas9 knockout, ultrastructure expansion microscopy, immunofluorescence\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined structural/cellular phenotype using multiple imaging modalities\",\n      \"pmids\": [\"40067174\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEDC2 localizes to centrosomes and its centrosomal localization is mutually dependent on TEDC1 and on delta-tubulin and epsilon-tubulin.\",\n      \"method\": \"Immunofluorescence localization in CRISPR knockout cell lines\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiment with functional epistasis across multiple KO lines\",\n      \"pmids\": [\"40067174\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A C-terminally truncated TEDC1 protein (produced by a frameshift variant) impairs binding with TEDC2, demonstrating that the TEDC1 C-terminus is required for the TEDC1–TEDC2 interaction.\",\n      \"method\": \"Patient-derived cell analysis, in vitro binding assay, exome sequencing\",\n      \"journal\": \"European journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — natural loss-of-function variant with defined binding defect, single study\",\n      \"pmids\": [\"39979680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Knockdown of TEDC2 inhibited proliferation, migration, and cancer stem cell maintenance in non-small cell lung cancer cells primarily through inhibition of the Hedgehog signaling pathway, and enhanced sensitivity to cisplatin in vitro and in vivo.\",\n      \"method\": \"siRNA/shRNA knockdown, functional assays (proliferation, migration, sphere formation), in vivo xenograft, pathway reporter assays\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — KD with defined phenotype and pathway placement, single lab, no direct biochemical interaction shown\",\n      \"pmids\": [\"41352505\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Knockdown of TEDC2 in lung adenocarcinoma cell lines slowed proliferation, migration, and invasion efficiency.\",\n      \"method\": \"siRNA knockdown, CCK8 proliferation assay, transwell migration/invasion assay\",\n      \"journal\": \"PeerJ\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, phenotypic KD data without pathway mechanism\",\n      \"pmids\": [\"39553728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Overexpression of TEDC2 promoted cell metastasis and proliferation in hepatocellular carcinoma cell lines in vitro, and TP53 mutations were found to regulate TEDC2 expression.\",\n      \"method\": \"Overexpression in HCC cell lines, proliferation and migration assays, bioinformatic correlation of TP53 mutation status with TEDC2 expression\",\n      \"journal\": \"Digestive and liver disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, in vitro overexpression phenotype; TP53-TEDC2 link is bioinformatic only\",\n      \"pmids\": [\"37867019\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEDC2 forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin at centrosomes; this complex is essential for centriole triplet microtubule architecture and structural integrity, as loss of any component causes abnormal centrioles that elongate but lack triplet microtubules and central core proteins and subsequently fragment during mitosis.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TEDC2 is a centrosomal protein that forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin, and this complex is essential for building and maintaining centriole triplet microtubule architecture [PMID:40067174]. Within the complex, TEDC1 and TEDC2 form a subcomplex whose assembly requires the TEDC1 C-terminus, and centrosomal localization of TEDC2 is mutually dependent on TEDC1, delta-tubulin, and epsilon-tubulin [PMID:40067174, PMID:39979680]. Loss of TEDC2 produces centrioles that lack triplet microtubules and central core scaffold proteins (e.g., POC5), exhibit an expanded proximal region, and undergo a futile cycle of elongation, fragmentation, and disintegration during mitosis [PMID:40067174]. TEDC2 knockdown in non-small cell lung cancer cells inhibits Hedgehog signaling and reduces proliferation and cancer stem cell maintenance [PMID:41352505].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Initial cancer-cell studies raised the question of whether TEDC2 has a general role in cell proliferation, showing that its overexpression promotes proliferation and migration in hepatocellular carcinoma cells.\",\n      \"evidence\": \"Overexpression and proliferation/migration assays in HCC cell lines\",\n      \"pmids\": [\"37867019\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single-lab overexpression study without mechanistic pathway identification\",\n        \"TP53–TEDC2 regulatory link is bioinformatic only, not validated experimentally\",\n        \"No biochemical or structural understanding of TEDC2 function\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Knockdown studies in lung adenocarcinoma cells corroborated that TEDC2 depletion impairs proliferation and migration, but still without identifying the underlying mechanism.\",\n      \"evidence\": \"siRNA knockdown with CCK8 proliferation and transwell assays in LUAD lines\",\n      \"pmids\": [\"39553728\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No pathway mechanism identified\",\n        \"Not independently confirmed outside a single lab\",\n        \"No connection to centriole biology yet established\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The core biochemical identity of TEDC2 was established: it forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin that localizes to centrosomes and is required for centriole triplet microtubule architecture, with loss causing centriole structural collapse and mitotic fragmentation.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, CRISPR/Cas9 knockout in human cells, ultrastructure expansion microscopy, AlphaFold Multimer modeling\",\n      \"pmids\": [\"40067174\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How the tetramer is recruited to the centriole and at what stage of centriole biogenesis it acts is unresolved\",\n        \"Stoichiometry and atomic-resolution structure of the endogenous complex have not been determined experimentally\",\n        \"Whether loss of triplet microtubules explains the proliferation defects seen in cancer knockdown studies is untested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The TEDC1–TEDC2 interaction interface was defined: a patient-derived TEDC1 C-terminal truncation disrupts binding to TEDC2, demonstrating that the TEDC1 C-terminus is required for subcomplex formation.\",\n      \"evidence\": \"Patient exome sequencing, in vitro binding assay with truncated TEDC1\",\n      \"pmids\": [\"39979680\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether this variant causes a Mendelian ciliopathy phenotype in patients has not been firmly established\",\n        \"Residue-level mapping of the TEDC1–TEDC2 binding interface is lacking\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A signaling pathway was linked to TEDC2's proliferative role: TEDC2 knockdown in NSCLC cells inhibited Hedgehog signaling, reduced cancer stem cell maintenance, and sensitized cells to cisplatin.\",\n      \"evidence\": \"siRNA/shRNA knockdown, Hedgehog pathway reporter assays, in vivo xenograft\",\n      \"pmids\": [\"41352505\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the Hedgehog link is a direct consequence of defective centriole/cilium architecture or an independent function is unknown\",\n        \"No direct biochemical interaction between TEDC2 and Hedgehog pathway components has been shown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include how the TEDC1–TEDC2–delta-tubulin–epsilon-tubulin tetramer is recruited to nascent centrioles, whether TEDC2 loss causes ciliopathy in humans, and whether the cancer-cell phenotypes are secondary to centriole/cilium defects.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experimental structure of the endogenous tetramer at atomic resolution\",\n        \"Mechanism linking centriole triplet microtubule loss to Hedgehog pathway suppression is unknown\",\n        \"In vivo organismal phenotype of TEDC2 loss in mammals has not been reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"TEDC1–TEDC2–delta-tubulin–epsilon-tubulin tetramer\"\n    ],\n    \"partners\": [\n      \"TEDC1\",\n      \"TUBD1\",\n      \"TUBE1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}