{"gene":"TANGO6","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2024,"finding":"TANGO6 associates with COPI vesicles via two transmembrane domains, and its N- and C-terminal cytoplasmic fragments capture RNA polymerase II subunit B (RPB2) in the cis-Golgi during G1 phase; COPI-docked TANGO6 then carries RPB2 to the ER and subsequently to the nucleus.","method":"Co-immunoprecipitation, subcellular fractionation, live-cell imaging, domain mutagenesis (transmembrane domain disruption)","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, fractionation, imaging, domain mutagenesis) in a single rigorous study establishing the molecular mechanism","pmids":["38490996"],"is_preprint":false},{"year":2024,"finding":"Functional disruption of TANGO6 prevents nuclear entry of RPB2, causing RPB2 to accumulate in the cytoplasm and resulting in cell cycle arrest in the G1 phase.","method":"TANGO6 knockdown/knockout with cell cycle analysis (flow cytometry) and subcellular localization of RPB2","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with defined molecular phenotype (RPB2 mislocalization) and defined cell cycle readout, multiple methods in one rigorous study","pmids":["38490996"],"is_preprint":false},{"year":2024,"finding":"Conditional depletion of TANGO6 in mouse hematopoietic stem cells results in compromised hematopoiesis, while overexpression results in expanded hematopoiesis, establishing TANGO6 as a regulator of hematopoietic stem cell proliferation.","method":"Conditional knockout and overexpression in mouse hematopoietic stem cells with hematopoietic phenotype readout","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean in vivo KO/OE with defined cellular phenotype, single lab study","pmids":["38490996"],"is_preprint":false},{"year":2025,"finding":"In zebrafish, tango6 deficiency causes a decline in RNA polymerase II subunit B levels and accumulation of DNA damage, which suppresses HSPC expansion in a P53-dependent manner; ikzf1 and cmyb are downstream P53 targets used by the Tango6-P53-Ikzf1/Cmyb axis in definitive haematopoiesis.","method":"Zebrafish homozygous tango6 mutant genetic screen, epistasis analysis (partial rescue by ikzf1 and cmyb overexpression in tango6 mutants), P53 pathway analysis","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with partial rescue, single lab, replicated mechanistic pathway from the 2024 study using an orthogonal model organism","pmids":["39620979"],"is_preprint":false},{"year":2023,"finding":"A germline heterozygous 23 kb CDH1-TANGO6 deletion removes regulatory elements downstream of CDH1 that interact with the CDH1 promoter (shown by 4C-seq and ATAC-seq); CRISPR-Cas9 cells mimicking this deletion show stronger CDH1 mRNA downregulation than CDH1-only deletion, indicating the deleted TANGO6-flanking region contains chromatin regulatory elements controlling CDH1 expression.","method":"ATAC-seq, 4C-seq, CRISPR-Cas9 deletion mimicry, RNA-seq","journal":"Gastric cancer","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal genomic and functional methods (4C-seq, ATAC-seq, CRISPR editing + RNA-seq), single lab; finding is primarily about CDH1 regulation but directly implicates the TANGO6 locus as a regulatory region","pmids":["37249750"],"is_preprint":false}],"current_model":"TANGO6 is a COPI vesicle-associated protein (anchored via two transmembrane domains) that captures RNA polymerase II subunit RPB2 at the cis-Golgi during G1 phase and mediates its transport through the ER to the nucleus; loss of TANGO6 traps RPB2 in the cytoplasm, causes DNA damage accumulation, activates P53, and arrests the cell cycle in G1, with downstream suppression of hematopoietic transcription factors Ikzf1/Cmyb explaining its essential role in hematopoietic stem cell proliferation and definitive haematopoiesis."},"narrative":{"mechanistic_narrative":"TANGO6 is a COPI vesicle-associated membrane protein that mediates the cytoplasm-to-nucleus delivery of RNA polymerase II subunit RPB2, a function essential for cell cycle progression and definitive hematopoiesis [PMID:38490996]. Anchored to COPI vesicles by two transmembrane domains, TANGO6 uses its N- and C-terminal cytoplasmic fragments to capture RPB2 at the cis-Golgi during G1 and ferries it through the ER to the nucleus [PMID:38490996]. Functional disruption of TANGO6 blocks RPB2 nuclear entry, trapping it in the cytoplasm and arresting cells in G1 [PMID:38490996]. This trafficking role underlies a hematopoietic stem cell function: conditional depletion in mouse HSCs compromises hematopoiesis while overexpression expands it [PMID:38490996], and in zebrafish tango6 loss lowers RPB2 levels and triggers DNA damage that suppresses HSPC expansion through a P53-dependent axis in which ikzf1 and cmyb act as downstream effectors [PMID:39620979]. The TANGO6 genomic locus additionally harbors chromatin regulatory elements that control CDH1 expression, independent of TANGO6 protein function [PMID:37249750].","teleology":[{"year":2023,"claim":"Before its protein function was known, the TANGO6 locus was implicated as a genomic region whose deletion alters expression of the neighboring CDH1 gene, raising the question of what regulatory elements it contains.","evidence":"ATAC-seq, 4C-seq, and CRISPR-Cas9 deletion mimicry with RNA-seq on a germline CDH1-TANGO6 deletion","pmids":["37249750"],"confidence":"Medium","gaps":["Does not address TANGO6 protein function","Effect is on CDH1 regulation, not on a TANGO6 gene product","Does not identify which specific elements drive CDH1 control"]},{"year":2024,"claim":"Established the core molecular mechanism: how RPB2 reaches the nucleus, by showing TANGO6 is a COPI vesicle-associated protein that captures RPB2 at the cis-Golgi in G1 and transports it via the ER to the nucleus.","evidence":"Co-immunoprecipitation, subcellular fractionation, live-cell imaging, and transmembrane domain mutagenesis","pmids":["38490996"],"confidence":"High","gaps":["Structural basis of RPB2 capture by the cytoplasmic fragments not resolved","Why a polymerase subunit transits the secretory pathway is unexplained","Generality across cell types not tested"]},{"year":2024,"claim":"Connected the trafficking defect to a cellular phenotype, showing loss of TANGO6 traps RPB2 in the cytoplasm and arrests the cell cycle in G1.","evidence":"TANGO6 knockdown/knockout with flow cytometry cell cycle analysis and RPB2 localization","pmids":["38490996"],"confidence":"High","gaps":["Mechanistic link between cytoplasmic RPB2 retention and G1 arrest not fully dissected","Whether other Pol II subunits are similarly affected unknown"]},{"year":2024,"claim":"Demonstrated physiological relevance, identifying TANGO6 as a dose-dependent regulator of hematopoietic stem cell proliferation in vivo.","evidence":"Conditional knockout and overexpression in mouse hematopoietic stem cells with hematopoietic readout","pmids":["38490996"],"confidence":"Medium","gaps":["Single-lab in vivo study","Whether the HSC phenotype is fully attributable to RPB2 trafficking not isolated"]},{"year":2025,"claim":"Defined the downstream signaling axis in an orthogonal organism, showing tango6 loss reduces RPB2, causes DNA damage, and suppresses HSPC expansion through P53 with ikzf1 and cmyb as effectors.","evidence":"Zebrafish tango6 mutant genetics, epistasis with partial rescue by ikzf1/cmyb overexpression, and P53 pathway analysis","pmids":["39620979"],"confidence":"Medium","gaps":["Rescue by ikzf1/cmyb is only partial","Direct causal chain from RPB2 decline to DNA damage not established","Single lab"]},{"year":null,"claim":"It remains unknown how a cytoplasmic RNA polymerase II subunit is recognized for COPI-dependent secretory-pathway transport and how this trafficking integrates with canonical nuclear import.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the TANGO6-RPB2 interaction","Recruitment/recognition determinants on RPB2 unknown","Relationship to classical nucleocytoplasmic transport machinery uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[0]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0]}],"complexes":[],"partners":["RPB2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9C0B7","full_name":"Transport and Golgi organization protein 6 homolog","aliases":["Transmembrane and coiled-coil domain-containing protein 7"],"length_aa":1094,"mass_kda":120.7,"function":"","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q9C0B7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TANGO6","classification":"Common Essential","n_dependent_lines":1202,"n_total_lines":1208,"dependency_fraction":0.9950331125827815},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DNAJC7","stoichiometry":0.2},{"gene":"POLR2B","stoichiometry":0.2},{"gene":"POLR2K","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TANGO6","total_profiled":1310},"omim":[{"mim_id":"620188","title":"TRANSPORT AND GOLGI ORGANIZATION 6 HOMOLOG; TANGO6","url":"https://www.omim.org/entry/620188"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TANGO6"},"hgnc":{"alias_symbol":["FLJ12688","KIAA1746"],"prev_symbol":["TMCO7"]},"alphafold":{"accession":"Q9C0B7","domains":[{"cath_id":"-","chopping":"15-31_42-115_137-235_247-267","consensus_level":"medium","plddt":85.1368,"start":15,"end":267},{"cath_id":"1.25.10.10","chopping":"910-1081","consensus_level":"high","plddt":88.6162,"start":910,"end":1081},{"cath_id":"1.20.1050","chopping":"409-550","consensus_level":"medium","plddt":86.1488,"start":409,"end":550}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9C0B7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9C0B7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9C0B7-F1-predicted_aligned_error_v6.png","plddt_mean":78.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TANGO6","jax_strain_url":"https://www.jax.org/strain/search?query=TANGO6"},"sequence":{"accession":"Q9C0B7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9C0B7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9C0B7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9C0B7"}},"corpus_meta":[{"pmid":"31062447","id":"PMC_31062447","title":"Whole-genome analysis identifying candidate genes of altitude adaptive ecological thresholds in yak populations.","date":"2019","source":"Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie","url":"https://pubmed.ncbi.nlm.nih.gov/31062447","citation_count":24,"is_preprint":false},{"pmid":"22363459","id":"PMC_22363459","title":"DISC1 conditioned GWAS for psychosis proneness in a large Finnish birth cohort.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22363459","citation_count":20,"is_preprint":false},{"pmid":"35501310","id":"PMC_35501310","title":"An epigenetic association analysis of childhood trauma in psychosis reveals possible overlap with methylation changes associated with PTSD.","date":"2022","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/35501310","citation_count":20,"is_preprint":false},{"pmid":"37249750","id":"PMC_37249750","title":"Combined loss of CDH1 and downstream regulatory sequences drive early-onset diffuse gastric cancer and increase penetrance of hereditary diffuse gastric cancer.","date":"2023","source":"Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association","url":"https://pubmed.ncbi.nlm.nih.gov/37249750","citation_count":8,"is_preprint":false},{"pmid":"38490996","id":"PMC_38490996","title":"TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38490996","citation_count":2,"is_preprint":false},{"pmid":"39620979","id":"PMC_39620979","title":"Tango6 regulates HSPC proliferation and definitive haematopoiesis via Ikzf1 and Cmyb in caudal haematopoietic tissue.","date":"2025","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/39620979","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5221,"output_tokens":1348,"usd":0.017941,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8019,"output_tokens":2251,"usd":0.048185,"stage2_stop_reason":"end_turn"},"total_usd":0.066126,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"TANGO6 associates with COPI vesicles via two transmembrane domains, and its N- and C-terminal cytoplasmic fragments capture RNA polymerase II subunit B (RPB2) in the cis-Golgi during G1 phase; COPI-docked TANGO6 then carries RPB2 to the ER and subsequently to the nucleus.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, live-cell imaging, domain mutagenesis (transmembrane domain disruption)\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, fractionation, imaging, domain mutagenesis) in a single rigorous study establishing the molecular mechanism\",\n      \"pmids\": [\"38490996\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Functional disruption of TANGO6 prevents nuclear entry of RPB2, causing RPB2 to accumulate in the cytoplasm and resulting in cell cycle arrest in the G1 phase.\",\n      \"method\": \"TANGO6 knockdown/knockout with cell cycle analysis (flow cytometry) and subcellular localization of RPB2\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with defined molecular phenotype (RPB2 mislocalization) and defined cell cycle readout, multiple methods in one rigorous study\",\n      \"pmids\": [\"38490996\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Conditional depletion of TANGO6 in mouse hematopoietic stem cells results in compromised hematopoiesis, while overexpression results in expanded hematopoiesis, establishing TANGO6 as a regulator of hematopoietic stem cell proliferation.\",\n      \"method\": \"Conditional knockout and overexpression in mouse hematopoietic stem cells with hematopoietic phenotype readout\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean in vivo KO/OE with defined cellular phenotype, single lab study\",\n      \"pmids\": [\"38490996\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In zebrafish, tango6 deficiency causes a decline in RNA polymerase II subunit B levels and accumulation of DNA damage, which suppresses HSPC expansion in a P53-dependent manner; ikzf1 and cmyb are downstream P53 targets used by the Tango6-P53-Ikzf1/Cmyb axis in definitive haematopoiesis.\",\n      \"method\": \"Zebrafish homozygous tango6 mutant genetic screen, epistasis analysis (partial rescue by ikzf1 and cmyb overexpression in tango6 mutants), P53 pathway analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with partial rescue, single lab, replicated mechanistic pathway from the 2024 study using an orthogonal model organism\",\n      \"pmids\": [\"39620979\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"A germline heterozygous 23 kb CDH1-TANGO6 deletion removes regulatory elements downstream of CDH1 that interact with the CDH1 promoter (shown by 4C-seq and ATAC-seq); CRISPR-Cas9 cells mimicking this deletion show stronger CDH1 mRNA downregulation than CDH1-only deletion, indicating the deleted TANGO6-flanking region contains chromatin regulatory elements controlling CDH1 expression.\",\n      \"method\": \"ATAC-seq, 4C-seq, CRISPR-Cas9 deletion mimicry, RNA-seq\",\n      \"journal\": \"Gastric cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal genomic and functional methods (4C-seq, ATAC-seq, CRISPR editing + RNA-seq), single lab; finding is primarily about CDH1 regulation but directly implicates the TANGO6 locus as a regulatory region\",\n      \"pmids\": [\"37249750\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TANGO6 is a COPI vesicle-associated protein (anchored via two transmembrane domains) that captures RNA polymerase II subunit RPB2 at the cis-Golgi during G1 phase and mediates its transport through the ER to the nucleus; loss of TANGO6 traps RPB2 in the cytoplasm, causes DNA damage accumulation, activates P53, and arrests the cell cycle in G1, with downstream suppression of hematopoietic transcription factors Ikzf1/Cmyb explaining its essential role in hematopoietic stem cell proliferation and definitive haematopoiesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TANGO6 is a COPI vesicle-associated membrane protein that mediates the cytoplasm-to-nucleus delivery of RNA polymerase II subunit RPB2, a function essential for cell cycle progression and definitive hematopoiesis [#0, #1]. Anchored to COPI vesicles by two transmembrane domains, TANGO6 uses its N- and C-terminal cytoplasmic fragments to capture RPB2 at the cis-Golgi during G1 and ferries it through the ER to the nucleus [#0]. Functional disruption of TANGO6 blocks RPB2 nuclear entry, trapping it in the cytoplasm and arresting cells in G1 [#1]. This trafficking role underlies a hematopoietic stem cell function: conditional depletion in mouse HSCs compromises hematopoiesis while overexpression expands it [#2], and in zebrafish tango6 loss lowers RPB2 levels and triggers DNA damage that suppresses HSPC expansion through a P53-dependent axis in which ikzf1 and cmyb act as downstream effectors [#3]. The TANGO6 genomic locus additionally harbors chromatin regulatory elements that control CDH1 expression, independent of TANGO6 protein function [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Before its protein function was known, the TANGO6 locus was implicated as a genomic region whose deletion alters expression of the neighboring CDH1 gene, raising the question of what regulatory elements it contains.\",\n      \"evidence\": \"ATAC-seq, 4C-seq, and CRISPR-Cas9 deletion mimicry with RNA-seq on a germline CDH1-TANGO6 deletion\",\n      \"pmids\": [\"37249750\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Does not address TANGO6 protein function\", \"Effect is on CDH1 regulation, not on a TANGO6 gene product\", \"Does not identify which specific elements drive CDH1 control\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established the core molecular mechanism: how RPB2 reaches the nucleus, by showing TANGO6 is a COPI vesicle-associated protein that captures RPB2 at the cis-Golgi in G1 and transports it via the ER to the nucleus.\",\n      \"evidence\": \"Co-immunoprecipitation, subcellular fractionation, live-cell imaging, and transmembrane domain mutagenesis\",\n      \"pmids\": [\"38490996\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Structural basis of RPB2 capture by the cytoplasmic fragments not resolved\", \"Why a polymerase subunit transits the secretory pathway is unexplained\", \"Generality across cell types not tested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected the trafficking defect to a cellular phenotype, showing loss of TANGO6 traps RPB2 in the cytoplasm and arrests the cell cycle in G1.\",\n      \"evidence\": \"TANGO6 knockdown/knockout with flow cytometry cell cycle analysis and RPB2 localization\",\n      \"pmids\": [\"38490996\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanistic link between cytoplasmic RPB2 retention and G1 arrest not fully dissected\", \"Whether other Pol II subunits are similarly affected unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated physiological relevance, identifying TANGO6 as a dose-dependent regulator of hematopoietic stem cell proliferation in vivo.\",\n      \"evidence\": \"Conditional knockout and overexpression in mouse hematopoietic stem cells with hematopoietic readout\",\n      \"pmids\": [\"38490996\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single-lab in vivo study\", \"Whether the HSC phenotype is fully attributable to RPB2 trafficking not isolated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the downstream signaling axis in an orthogonal organism, showing tango6 loss reduces RPB2, causes DNA damage, and suppresses HSPC expansion through P53 with ikzf1 and cmyb as effectors.\",\n      \"evidence\": \"Zebrafish tango6 mutant genetics, epistasis with partial rescue by ikzf1/cmyb overexpression, and P53 pathway analysis\",\n      \"pmids\": [\"39620979\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Rescue by ikzf1/cmyb is only partial\", \"Direct causal chain from RPB2 decline to DNA damage not established\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how a cytoplasmic RNA polymerase II subunit is recognized for COPI-dependent secretory-pathway transport and how this trafficking integrates with canonical nuclear import.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No structural model of the TANGO6-RPB2 interaction\", \"Recruitment/recognition determinants on RPB2 unknown\", \"Relationship to classical nucleocytoplasmic transport machinery uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RPB2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":5,"faith_pct":80.0}}