{"gene":"NUP205","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":2003,"finding":"C. elegans Nup205 (NPP-3) is required for normal NPC distribution in the nuclear envelope and for establishing the size-exclusion limit of the NPC in vivo. Depletion of Nup205 by RNAi caused failure in nuclear exclusion of ~70 kDa macromolecules without preventing active nuclear protein import or nuclear envelope assembly, and resulted in abnormal chromatin condensation and embryonic arrest.","method":"RNAi depletion in C. elegans embryos with fluorescent size-exclusion assays and nuclear import assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — clean loss-of-function with defined molecular phenotype (size exclusion), replicated across multiple nucleoporins in same study","pmids":["12937276"],"is_preprint":false},{"year":2004,"finding":"Nup205 localizes to the core scaffold of the vertebrate NPC (between the two coaxial rings) by immunoelectron microscopy. RNAi-mediated silencing of Nup205 in HeLa cells demonstrated it is important for long-term maintenance of NPCs but initially dispensable for anchoring of nuclear basket components Nup153 and Tpr.","method":"Postembedding immunoelectron microscopy and RNAi in HeLa cells","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — direct structural localization by IEM combined with functional RNAi knockdown, orthogonal methods","pmids":["15229283"],"is_preprint":false},{"year":2012,"finding":"Nup205 (NPP-3) is lost from the nuclear envelope in the vicinity of centrosomes at the onset of mitosis in C. elegans embryos. Centrosomes are both necessary and sufficient for this local loss, which also requires Aurora-A kinase (AIR-1) activity. NPP-3 negatively modulates the timing of mitotic onset, and its removal by centrosomes/AIR-1 promotes timely mitotic entry.","method":"RNAi modifier screen, live imaging, centrosome ablation/addition experiments, Aurora-A kinase inhibition in C. elegans embryos","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal genetic and cell-biological approaches establishing necessity and sufficiency","pmids":["22740626"],"is_preprint":false},{"year":2014,"finding":"BioID proximity labeling applied to Nup93 complex constituents (which includes Nup205) revealed the spatial organization of Nup205 within the human NPC scaffold, consistent with its position in the inner ring/Nup93 subcomplex.","method":"Proximity-dependent biotinylation (BioID) fused to NPC constituents in living human cells, followed by mass spectrometry","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 — BioID in living cells providing spatial information, but NUP205-specific findings are part of a larger screen","pmids":["24927568"],"is_preprint":false},{"year":2016,"finding":"Mutations in NUP205 cause steroid-resistant nephrotic syndrome (SRNS). A NUP205 alteration abrogates its interaction with NUP93, and NUP93 knockdown reduces NUP205 presence in the NPC, establishing a reciprocal interdependence between NUP93 and NUP205 for NPC assembly.","method":"Human genetics (exome sequencing), Co-IP/interaction assays, knockdown studies in podocytes","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 — reciprocal interaction data combined with disease genetics and knockdown phenotype, published in high-impact journal","pmids":["26878725"],"is_preprint":false},{"year":2016,"finding":"Nup205 assists Nup93 in repressing the HOXA gene cluster. Nup93 and its interactors Nup188 and Nup205 associate with HOXA gene promoters; depletion of this sub-complex disengages the HOXA locus from the nuclear periphery, increases active histone marks (H3K9ac), decreases repressive marks (H3K27me3), and upregulates HOXA gene expression.","method":"ChIP, RNAi knockdown, 3D-FISH, histone modification analysis in DLD1 cells","journal":"Epigenetics & chromatin","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (ChIP, FISH, histone marks) but Nup205 role is secondary to Nup93 in this study","pmids":["27980680"],"is_preprint":false},{"year":2020,"finding":"NEK3 kinase regulates NUP205 protein levels; biallelic loss-of-function NEK3 mutations in patients significantly downregulate inner ring NPC components including NUP205, NUP188, and NUP155. NEK3 silencing in RPE cells recapitulated this downregulation, linking NUP205 abundance to NEK3 kinase activity.","method":"Whole-exome sequencing, siRNA knockdown, western blot, transcriptome analysis in RPE cells","journal":"Cell death & disease","confidence":"Low","confidence_rationale":"Tier 3 — indirect relationship; NUP205 downregulation is a downstream consequence, mechanism of regulation not directly established","pmids":["33230144"],"is_preprint":false},{"year":2023,"finding":"NUP205 physically interacts with YAP and TAZ (Hippo pathway transcriptional effectors) in podocytes as identified by unbiased interactome mass spectrometry. NUP205 is essential for YAP/TAZ nuclear import; its depletion reduces nuclear YAP/TAZ interaction with TEAD1 and their transcriptional activity. A feedback loop exists whereby TAZ-mediated regulation of NUP205 expression modulates YAP activity.","method":"Quantitative label-free mass spectrometry interactome, NUP205 knockdown with nuclear/cytoplasmic fractionation, transcriptional reporter assays, Co-IP in podocytes","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — unbiased interactome combined with functional knockdown and multiple readouts (localization, transcriptional activity, feedback)","pmids":["37565816"],"is_preprint":false},{"year":2026,"finding":"NUP205 stabilizes YAP1 protein via the ubiquitin-proteasome pathway in hepatocellular carcinoma cells. NUP205 knockdown inhibited cell proliferation and induced apoptosis, while overexpression had opposing effects; these phenotypes were mediated through YAP1 protein stability.","method":"NUP205 knockdown/overexpression, ubiquitin-proteasome pathway assays, xenograft mouse model, proliferation and apoptosis assays in HCC cells","journal":"Journal of hepatocellular carcinoma","confidence":"Medium","confidence_rationale":"Tier 2 — functional KD/OE with defined pathway (ubiquitin-proteasome/YAP1 stabilization) and in vivo validation, single lab","pmids":["41868261"],"is_preprint":false},{"year":2022,"finding":"Knockdown of NUP205 in human lung (A549) cells suppresses influenza A virus (H1N1) reproduction, reducing viral titer by ~2 log units and viral RNA concentration up to 30-fold, indicating NUP205 is required for efficient influenza virus replication.","method":"siRNA knockdown, viral titer measurement, hemagglutination assay, RT-PCR quantification of viral RNA in A549 cells","journal":"Infectious disorders drug targets","confidence":"Low","confidence_rationale":"Tier 3 — single lab, knockdown phenotype without defined molecular mechanism linking NUP205 to viral lifecycle","pmids":["35339191"],"is_preprint":false}],"current_model":"NUP205 is a scaffold nucleoporin of the inner ring (Nup93 sub-complex) of the nuclear pore complex that is required for normal NPC size-exclusion gating and long-term NPC maintenance; it physically interacts with NUP93 (mutually required for NPC assembly), is removed from the nuclear envelope near centrosomes at mitotic onset in an Aurora-A-dependent manner, participates with NUP93/NUP188 in tethering and repressing the HOXA gene cluster at the nuclear periphery, mediates nuclear import of YAP and TAZ (Hippo pathway effectors) in podocytes, and stabilizes YAP1 protein via the ubiquitin-proteasome pathway in hepatocellular carcinoma cells, with loss-of-function mutations causing steroid-resistant nephrotic syndrome through disrupted NUP93 interaction and aberrant SMAD/YAP-TAZ signaling."},"narrative":{"teleology":[{"year":2003,"claim":"The first functional characterization of Nup205 revealed that, beyond structural scaffolding, it is specifically required for the NPC's passive diffusion barrier — resolving whether individual inner-ring nucleoporins have discrete transport roles.","evidence":"RNAi depletion in C. elegans embryos with fluorescent size-exclusion and nuclear import assays","pmids":["12937276"],"confidence":"High","gaps":["Mechanism by which Nup205 establishes size exclusion not defined","Vertebrate validation of size-exclusion role not performed"]},{"year":2004,"claim":"Immunoelectron microscopy placed Nup205 at the core scaffold between the NPC's coaxial rings and RNAi showed it is dispensable for initial NPC assembly but required for long-term NPC maintenance, distinguishing its role from early-acting assembly factors.","evidence":"Postembedding immunoelectron microscopy and RNAi knockdown in HeLa cells","pmids":["15229283"],"confidence":"High","gaps":["Structural contacts with neighboring nucleoporins not resolved at molecular level","Mechanism of NPC destabilization upon Nup205 loss not identified"]},{"year":2012,"claim":"Discovery that Nup205 is selectively removed from the nuclear envelope near centrosomes at mitotic onset via Aurora-A kinase revealed an unexpected cell-cycle regulatory function — Nup205 negatively modulates mitotic entry timing.","evidence":"Live imaging, centrosome ablation/addition, Aurora-A inhibition, and RNAi modifier screen in C. elegans embryos","pmids":["22740626"],"confidence":"High","gaps":["Direct phosphorylation sites on Nup205 by Aurora-A not identified","Whether this mitotic role is conserved in vertebrates not tested"]},{"year":2014,"claim":"BioID proximity labeling in living human cells confirmed Nup205's spatial position within the Nup93 sub-complex at the inner ring, providing an in vivo interaction map complementing earlier EM data.","evidence":"BioID-mass spectrometry of NPC constituents in human cells","pmids":["24927568"],"confidence":"Medium","gaps":["Proximity does not prove direct binding; stoichiometry of interactions not resolved","NUP205-specific contacts versus shared inner-ring contacts not distinguished"]},{"year":2016,"claim":"Human genetic studies established NUP205 as a disease gene: mutations causing steroid-resistant nephrotic syndrome abrogate the NUP93–NUP205 interaction, and reciprocal knockdown demonstrated mutual dependence for NPC assembly, linking NPC structural integrity to podocyte function.","evidence":"Exome sequencing of SRNS families, co-immunoprecipitation, and NUP93 knockdown in podocytes","pmids":["26878725"],"confidence":"High","gaps":["Which specific NPC transport pathways are disrupted in patient podocytes not defined","Whether other organ phenotypes arise from NUP205 mutations not systematically assessed"]},{"year":2016,"claim":"A gene-regulatory role was established: NUP205, together with NUP93 and NUP188, associates with HOXA promoters and tethers the HOXA locus to the nuclear periphery to maintain a repressive chromatin state, showing inner-ring nucleoporins directly participate in transcriptional regulation.","evidence":"ChIP, 3D-FISH, histone modification analysis, and RNAi in DLD1 cells","pmids":["27980680"],"confidence":"Medium","gaps":["NUP205's individual contribution versus NUP93's dominant role not cleanly separated","Whether other genomic loci are similarly regulated is unknown","Whether tethering requires NUP205's NPC-embedded state or occurs off-pore not determined"]},{"year":2023,"claim":"Unbiased interactomics in podocytes identified YAP and TAZ as NUP205 physical interactors and demonstrated that NUP205 is essential for their nuclear import and TEAD1-dependent transcriptional activity, connecting NPC function to Hippo signaling and providing a mechanistic link to the nephrotic syndrome phenotype.","evidence":"Label-free mass spectrometry interactome, NUP205 knockdown with nuclear/cytoplasmic fractionation, transcriptional reporter assays, and co-IP in podocytes","pmids":["37565816"],"confidence":"High","gaps":["Whether NUP205 acts as a direct transport receptor or facilitates FG-repeat-mediated translocation of YAP/TAZ not resolved","TAZ-NUP205 feedback loop mechanism not fully characterized"]},{"year":2026,"claim":"In hepatocellular carcinoma, NUP205 was shown to stabilize YAP1 protein through the ubiquitin-proteasome pathway, extending its Hippo-pathway connection to an oncogenic context and demonstrating NUP205 influences YAP not only through nuclear import but also through protein turnover.","evidence":"NUP205 knockdown/overexpression, proteasome pathway assays, xenograft models, proliferation and apoptosis assays in HCC cells","pmids":["41868261"],"confidence":"Medium","gaps":["The E3 ubiquitin ligase involved in YAP1 destabilization upon NUP205 loss not identified","Whether YAP1 stabilization is direct or mediated through an intermediary not established","Single-lab finding awaiting independent replication"]},{"year":null,"claim":"Key unresolved questions include: the structural basis of NUP205 within the human inner ring at atomic resolution, the direct phosphorylation events mediating its mitotic removal, and whether its selective transport and gene-regulatory functions operate through its NPC-embedded form or a soluble nucleoplasmic pool.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of human NUP205 in the NPC context","Mechanism discriminating NPC-dependent versus NPC-independent functions not established","Aurora-A phosphorylation sites on NUP205 not mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0,7]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[1,2,3,4]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,3]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[7,8]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,7]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[5]}],"complexes":["Nup93 sub-complex (inner ring)","Nuclear pore complex (NPC)"],"partners":["NUP93","NUP188","YAP1","TAZ","TEAD1"],"other_free_text":[]},"mechanistic_narrative":"NUP205 is a scaffold nucleoporin of the inner ring (Nup93 sub-complex) of the nuclear pore complex, essential for NPC size-exclusion gating, long-term NPC maintenance, and regulated nuclear transport. It resides in the core NPC scaffold between the two coaxial rings, where it is reciprocally interdependent with NUP93 for NPC assembly; disease-causing mutations that disrupt NUP93 binding cause steroid-resistant nephrotic syndrome [PMID:26878725, PMID:15229283]. NUP205 participates in gene regulation by tethering the HOXA gene cluster at the nuclear periphery with NUP93/NUP188 to maintain a repressive chromatin state, and it mediates nuclear import of the Hippo pathway effectors YAP and TAZ, coupling NPC function to transcriptional signaling in podocytes [PMID:27980680, PMID:37565816]. At mitotic onset, NUP205 is removed from the nuclear envelope near centrosomes in an Aurora-A kinase–dependent manner, acting as a negative modulator of mitotic entry timing [PMID:22740626]."},"prefetch_data":{"uniprot":{"accession":"Q92621","full_name":"Nuclear pore complex protein Nup205","aliases":["205 kDa nucleoporin","Nucleoporin Nup205"],"length_aa":2012,"mass_kda":227.9,"function":"Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor NUP62 and other nucleoporins, but not NUP153 and TPR, to the NPC (PubMed:15229283). In association with TMEM209, may be involved in nuclear transport of various nuclear proteins in addition to MYC (PubMed:22719065)","subcellular_location":"Nucleus membrane; Nucleus, nuclear pore complex","url":"https://www.uniprot.org/uniprotkb/Q92621/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP205","classification":"Common Essential","n_dependent_lines":1161,"n_total_lines":1208,"dependency_fraction":0.9610927152317881},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CLIP1","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP205","total_profiled":1310},"omim":[{"mim_id":"616893","title":"NEPHROTIC SYNDROME, TYPE 13; NPHS13","url":"https://www.omim.org/entry/616893"},{"mim_id":"616892","title":"NEPHROTIC SYNDROME, TYPE 12; NPHS12","url":"https://www.omim.org/entry/616892"},{"mim_id":"615587","title":"NUCLEOPORIN, 188-KD; NUP188","url":"https://www.omim.org/entry/615587"},{"mim_id":"614352","title":"NUCLEOPORIN, 205-KD; NUP205","url":"https://www.omim.org/entry/614352"},{"mim_id":"614351","title":"NUCLEOPORIN, 93-KD; NUP93","url":"https://www.omim.org/entry/614351"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP205"},"hgnc":{"alias_symbol":["KIAA0225"],"prev_symbol":["C7orf14"]},"alphafold":{"accession":"Q92621","domains":[{"cath_id":"-","chopping":"8-240","consensus_level":"medium","plddt":83.7054,"start":8,"end":240},{"cath_id":"-","chopping":"241-383","consensus_level":"medium","plddt":83.9169,"start":241,"end":383},{"cath_id":"-","chopping":"719-869","consensus_level":"medium","plddt":88.2005,"start":719,"end":869},{"cath_id":"-","chopping":"907-1050","consensus_level":"high","plddt":80.5626,"start":907,"end":1050},{"cath_id":"-","chopping":"1316-1358_1399-1433","consensus_level":"medium","plddt":82.9359,"start":1316,"end":1433},{"cath_id":"1.25.40","chopping":"1459-1594_1611-1636","consensus_level":"medium","plddt":86.3301,"start":1459,"end":1636},{"cath_id":"1.20.1050","chopping":"1788-1792_1806-1918_1953-2009","consensus_level":"high","plddt":76.9281,"start":1788,"end":2009}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92621","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92621-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92621-F1-predicted_aligned_error_v6.png","plddt_mean":78.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP205","jax_strain_url":"https://www.jax.org/strain/search?query=NUP205"},"sequence":{"accession":"Q92621","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92621.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92621/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92621"}},"corpus_meta":[{"pmid":"12937276","id":"PMC_12937276","title":"Caenorhabditis 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cell","url":"https://pubmed.ncbi.nlm.nih.gov/15229283","citation_count":194,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7551,"output_tokens":1727,"usd":0.024279},"stage2":{"model":"claude-opus-4-6","input_tokens":4982,"output_tokens":2001,"usd":0.112403},"total_usd":0.319061,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":19151,"output_tokens":2547,"usd":0.047829},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":6095,"output_tokens":2369,"usd":0.13455}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"C. elegans Nup205 (NPP-3) is required for normal NPC distribution in the nuclear envelope and for nuclear size exclusion of ~70 kDa macromolecules; RNAi depletion causes failure of nuclear exclusion without preventing active nuclear protein import or nuclear envelope assembly, demonstrating Nup205 contributes to NPC structural integrity.\",\n      \"method\": \"RNAi knockdown in C. elegans embryos with live imaging and nuclear exclusion assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype, replicated across multiple nucleoporins, 159 citations\",\n      \"pmids\": [\"12937276\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"C. elegans Nup205 (NPP-3) is lost from the nuclear envelope near centrosomes at mitotic onset, and this local loss requires both centrosome activity and Aurora-A kinase (AIR-1); Nup205 negatively modulates the timing of mitotic onset, and its removal by centrosomes/AIR-1 promotes timely entry into mitosis.\",\n      \"method\": \"RNAi modifier screen in C. elegans embryos, live imaging, centrosome ablation experiments, Aurora-A kinase epistasis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (RNAi, live imaging, genetic epistasis with Aurora-A), moderate evidence\",\n      \"pmids\": [\"22740626\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NUP205 physically interacts with NUP93 at the NPC; NUP93 knockdown reduces NUP205 presence in the NPC, and a NUP205 disease-associated alteration abrogates NUP93 interaction, establishing NUP93 as required for NUP205 NPC assembly/retention.\",\n      \"method\": \"Reciprocal co-immunoprecipitation, NUP205 knockdown, NPC assembly assays in patient-derived cells\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with functional validation in disease context, 156 citations\",\n      \"pmids\": [\"26878725\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Nup205 assists Nup93 in mediating transcriptional repression of the HOXA gene cluster by tethering it to the nuclear periphery; depletion of the Nup93/Nup188/Nup205 sub-complex disengages HOXA from the nuclear periphery, increases active histone marks (H3K9ac), decreases repressive marks (H3K27me3), and upregulates HOXA gene expression.\",\n      \"method\": \"siRNA knockdown, ChIP, 3D-FISH, histone mark analysis in DLD1 cells\",\n      \"journal\": \"Epigenetics & chromatin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods but single lab study\",\n      \"pmids\": [\"27980680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NUP205 is a component of YAP and TAZ protein complexes in podocytes (identified by quantitative label-free mass spectrometry interactome), and NUP205 is essential for YAP/TAZ nuclear import; NUP205 loss reduces nuclear YAP/TAZ interaction with TEAD1 and their transcriptional activity. A feedback loop exists whereby TAZ regulates NUP205 expression to modulate YAP activity.\",\n      \"method\": \"Unbiased quantitative label-free mass spectrometry interactome, NUP205 knockdown with nuclear import assays, transcriptional reporter assays in podocytes\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — unbiased MS interactome plus functional nuclear import and transcriptional activity assays, multiple orthogonal methods in single study\",\n      \"pmids\": [\"37565816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"NUP205 stabilizes YAP1 protein via the ubiquitin-proteasome pathway in hepatocellular carcinoma cells; NUP205 knockdown reduces YAP1 protein stability and suppresses HCC cell proliferation and tumor growth in vivo, while NUP205 overexpression has opposing effects.\",\n      \"method\": \"NUP205 knockdown and overexpression in HCC cell lines and xenograft mouse model, ubiquitin-proteasome pathway inhibition assays, YAP1 protein stability assessment\",\n      \"journal\": \"Journal of hepatocellular carcinoma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD/OE with in vivo validation and proteasome pathway mechanistic follow-up, single lab\",\n      \"pmids\": [\"41868261\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NUP205 knockdown by siRNA significantly suppresses influenza A virus (H1N1) reproduction in human lung cells, reducing viral titer and viral RNA concentration, indicating NUP205 is required for efficient influenza virus replication.\",\n      \"method\": \"siRNA knockdown in A549 cells, viral titer measurement, hemagglutination assay, RT-PCR for viral RNA\",\n      \"journal\": \"Infectious disorders drug targets\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single method, no mechanistic pathway defined for how NUP205 supports viral replication\",\n      \"pmids\": [\"35339191\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP205 is a structural inner-ring nucleoporin that depends on NUP93 for its NPC assembly/retention, contributes to NPC size-exclusion function (~70 kDa), is locally removed from the nuclear envelope near centrosomes via Aurora-A kinase to promote mitotic onset, assists Nup93 in tethering and repressing the HOXA gene cluster at the nuclear periphery, is essential for YAP/TAZ nuclear import and transcriptional activity in podocytes, and stabilizes YAP1 protein via the ubiquitin-proteasome pathway in cancer cells.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"C. elegans Nup205 (NPP-3) is required for normal NPC distribution in the nuclear envelope and for establishing the size-exclusion limit of the NPC in vivo. Depletion of Nup205 by RNAi caused failure in nuclear exclusion of ~70 kDa macromolecules without preventing active nuclear protein import or nuclear envelope assembly, and resulted in abnormal chromatin condensation and embryonic arrest.\",\n      \"method\": \"RNAi depletion in C. elegans embryos with fluorescent size-exclusion assays and nuclear import assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean loss-of-function with defined molecular phenotype (size exclusion), replicated across multiple nucleoporins in same study\",\n      \"pmids\": [\"12937276\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Nup205 localizes to the core scaffold of the vertebrate NPC (between the two coaxial rings) by immunoelectron microscopy. RNAi-mediated silencing of Nup205 in HeLa cells demonstrated it is important for long-term maintenance of NPCs but initially dispensable for anchoring of nuclear basket components Nup153 and Tpr.\",\n      \"method\": \"Postembedding immunoelectron microscopy and RNAi in HeLa cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct structural localization by IEM combined with functional RNAi knockdown, orthogonal methods\",\n      \"pmids\": [\"15229283\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Nup205 (NPP-3) is lost from the nuclear envelope in the vicinity of centrosomes at the onset of mitosis in C. elegans embryos. Centrosomes are both necessary and sufficient for this local loss, which also requires Aurora-A kinase (AIR-1) activity. NPP-3 negatively modulates the timing of mitotic onset, and its removal by centrosomes/AIR-1 promotes timely mitotic entry.\",\n      \"method\": \"RNAi modifier screen, live imaging, centrosome ablation/addition experiments, Aurora-A kinase inhibition in C. elegans embryos\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal genetic and cell-biological approaches establishing necessity and sufficiency\",\n      \"pmids\": [\"22740626\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"BioID proximity labeling applied to Nup93 complex constituents (which includes Nup205) revealed the spatial organization of Nup205 within the human NPC scaffold, consistent with its position in the inner ring/Nup93 subcomplex.\",\n      \"method\": \"Proximity-dependent biotinylation (BioID) fused to NPC constituents in living human cells, followed by mass spectrometry\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — BioID in living cells providing spatial information, but NUP205-specific findings are part of a larger screen\",\n      \"pmids\": [\"24927568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Mutations in NUP205 cause steroid-resistant nephrotic syndrome (SRNS). A NUP205 alteration abrogates its interaction with NUP93, and NUP93 knockdown reduces NUP205 presence in the NPC, establishing a reciprocal interdependence between NUP93 and NUP205 for NPC assembly.\",\n      \"method\": \"Human genetics (exome sequencing), Co-IP/interaction assays, knockdown studies in podocytes\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction data combined with disease genetics and knockdown phenotype, published in high-impact journal\",\n      \"pmids\": [\"26878725\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Nup205 assists Nup93 in repressing the HOXA gene cluster. Nup93 and its interactors Nup188 and Nup205 associate with HOXA gene promoters; depletion of this sub-complex disengages the HOXA locus from the nuclear periphery, increases active histone marks (H3K9ac), decreases repressive marks (H3K27me3), and upregulates HOXA gene expression.\",\n      \"method\": \"ChIP, RNAi knockdown, 3D-FISH, histone modification analysis in DLD1 cells\",\n      \"journal\": \"Epigenetics & chromatin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (ChIP, FISH, histone marks) but Nup205 role is secondary to Nup93 in this study\",\n      \"pmids\": [\"27980680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NEK3 kinase regulates NUP205 protein levels; biallelic loss-of-function NEK3 mutations in patients significantly downregulate inner ring NPC components including NUP205, NUP188, and NUP155. NEK3 silencing in RPE cells recapitulated this downregulation, linking NUP205 abundance to NEK3 kinase activity.\",\n      \"method\": \"Whole-exome sequencing, siRNA knockdown, western blot, transcriptome analysis in RPE cells\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — indirect relationship; NUP205 downregulation is a downstream consequence, mechanism of regulation not directly established\",\n      \"pmids\": [\"33230144\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NUP205 physically interacts with YAP and TAZ (Hippo pathway transcriptional effectors) in podocytes as identified by unbiased interactome mass spectrometry. NUP205 is essential for YAP/TAZ nuclear import; its depletion reduces nuclear YAP/TAZ interaction with TEAD1 and their transcriptional activity. A feedback loop exists whereby TAZ-mediated regulation of NUP205 expression modulates YAP activity.\",\n      \"method\": \"Quantitative label-free mass spectrometry interactome, NUP205 knockdown with nuclear/cytoplasmic fractionation, transcriptional reporter assays, Co-IP in podocytes\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — unbiased interactome combined with functional knockdown and multiple readouts (localization, transcriptional activity, feedback)\",\n      \"pmids\": [\"37565816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"NUP205 stabilizes YAP1 protein via the ubiquitin-proteasome pathway in hepatocellular carcinoma cells. NUP205 knockdown inhibited cell proliferation and induced apoptosis, while overexpression had opposing effects; these phenotypes were mediated through YAP1 protein stability.\",\n      \"method\": \"NUP205 knockdown/overexpression, ubiquitin-proteasome pathway assays, xenograft mouse model, proliferation and apoptosis assays in HCC cells\",\n      \"journal\": \"Journal of hepatocellular carcinoma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional KD/OE with defined pathway (ubiquitin-proteasome/YAP1 stabilization) and in vivo validation, single lab\",\n      \"pmids\": [\"41868261\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Knockdown of NUP205 in human lung (A549) cells suppresses influenza A virus (H1N1) reproduction, reducing viral titer by ~2 log units and viral RNA concentration up to 30-fold, indicating NUP205 is required for efficient influenza virus replication.\",\n      \"method\": \"siRNA knockdown, viral titer measurement, hemagglutination assay, RT-PCR quantification of viral RNA in A549 cells\",\n      \"journal\": \"Infectious disorders drug targets\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, knockdown phenotype without defined molecular mechanism linking NUP205 to viral lifecycle\",\n      \"pmids\": [\"35339191\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP205 is a scaffold nucleoporin of the inner ring (Nup93 sub-complex) of the nuclear pore complex that is required for normal NPC size-exclusion gating and long-term NPC maintenance; it physically interacts with NUP93 (mutually required for NPC assembly), is removed from the nuclear envelope near centrosomes at mitotic onset in an Aurora-A-dependent manner, participates with NUP93/NUP188 in tethering and repressing the HOXA gene cluster at the nuclear periphery, mediates nuclear import of YAP and TAZ (Hippo pathway effectors) in podocytes, and stabilizes YAP1 protein via the ubiquitin-proteasome pathway in hepatocellular carcinoma cells, with loss-of-function mutations causing steroid-resistant nephrotic syndrome through disrupted NUP93 interaction and aberrant SMAD/YAP-TAZ signaling.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP205 is an inner-ring nucleoporin that contributes to nuclear pore complex (NPC) structural integrity, selective nucleocytoplasmic transport, chromatin organization at the nuclear periphery, and mitotic timing. NUP205 requires NUP93 for its incorporation into the NPC, and disease-associated NUP205 mutations that abrogate NUP93 binding impair NPC assembly [PMID:26878725]; its depletion compromises NPC size-exclusion of ~70 kDa macromolecules without blocking active import [PMID:12937276]. As part of the Nup93/Nup188/Nup205 sub-complex, NUP205 tethers the HOXA gene cluster to the nuclear periphery and maintains its transcriptional repression through enforcement of repressive histone marks [PMID:27980680]. NUP205 is selectively removed from the nuclear envelope near centrosomes by Aurora-A kinase to promote timely mitotic entry [PMID:22740626], and it is essential for YAP/TAZ nuclear import and transcriptional activity in podocytes, with a feedback loop in which TAZ regulates NUP205 expression [PMID:37565816].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing that NUP205 is a structural nucleoporin required for NPC barrier function—not just assembly—resolved whether inner-ring nucleoporins contribute to the passive diffusion limit of the pore.\",\n      \"evidence\": \"RNAi depletion of C. elegans NPP-3 (Nup205) with live imaging and nuclear exclusion assays in embryos\",\n      \"pmids\": [\"12937276\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which NUP205 contributes to size-exclusion (direct barrier vs. FG-Nup organization) is undefined\",\n        \"Whether the ~70 kDa exclusion limit phenotype is conserved in vertebrates was not tested\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstrating that NUP205 is locally removed from the nuclear envelope near centrosomes by Aurora-A kinase to permit mitotic onset revealed a novel link between NPC composition and cell-cycle timing.\",\n      \"evidence\": \"RNAi modifier screen, live imaging, centrosome ablation, and Aurora-A epistasis in C. elegans embryos\",\n      \"pmids\": [\"22740626\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Aurora-A directly phosphorylates NUP205 or acts through an intermediary is unknown\",\n        \"Conservation of this centrosome–NUP205 mitotic timing mechanism in mammals is untested\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identifying NUP93 as the direct binding partner required for NUP205 NPC incorporation, and showing a disease-associated NUP205 mutation that disrupts this interaction, defined the assembly dependency hierarchy of the inner ring and linked it to human disease.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation and NPC assembly analysis in patient-derived cells\",\n      \"pmids\": [\"26878725\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the NUP205–NUP93 interface is not resolved at atomic level\",\n        \"Whether other inner-ring nucleoporins can partially compensate for NUP205 loss is unknown\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showing that the Nup93/Nup188/Nup205 sub-complex tethers the HOXA gene cluster to the nuclear periphery and enforces repressive chromatin marks extended NUP205's role from transport barrier to gene regulation.\",\n      \"evidence\": \"siRNA knockdown, ChIP for histone marks, and 3D-FISH in DLD1 cells\",\n      \"pmids\": [\"27980680\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether NUP205 contacts chromatin directly or only through NUP93 is unresolved\",\n        \"Genome-wide scope of NUP205-dependent gene tethering beyond HOXA is unknown\",\n        \"Single-lab study; independent replication needed\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying NUP205 as a component of YAP/TAZ protein complexes that is essential for their nuclear import and transcriptional activity established a specific cargo-dependent transport role and a regulatory feedback loop in podocytes.\",\n      \"evidence\": \"Label-free quantitative mass spectrometry interactome, NUP205 knockdown with nuclear import and transcriptional reporter assays in podocytes\",\n      \"pmids\": [\"37565816\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether NUP205 acts as a direct import receptor or facilitates transport indirectly is unclear\",\n        \"Whether this NUP205–YAP/TAZ axis operates outside podocytes is not addressed\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrating that NUP205 stabilizes YAP1 protein through the ubiquitin-proteasome pathway in hepatocellular carcinoma extended the NUP205–YAP axis to cancer biology and defined a post-translational mechanism of YAP regulation.\",\n      \"evidence\": \"NUP205 knockdown/overexpression in HCC cell lines and xenograft mouse model with proteasome inhibition assays\",\n      \"pmids\": [\"41868261\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The E3 ubiquitin ligase whose activity is modulated by NUP205 is not identified\",\n        \"Whether NUP205 stabilizes YAP1 through direct physical interaction or indirectly via nuclear import is unresolved\",\n        \"Single-lab finding awaiting independent confirmation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and mechanistic model explaining how NUP205 integrates NPC barrier function, selective cargo transport (YAP/TAZ), chromatin tethering, and mitotic regulation remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of NUP205 in the context of the human NPC inner ring\",\n        \"Whether NUP205's roles in YAP transport, chromatin tethering, and mitotic timing are mechanistically separable is unknown\",\n        \"Direct phosphorylation sites on NUP205 (e.g., by Aurora-A) have not been mapped\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"Nup93/Nup188/Nup205 inner-ring sub-complex\"\n    ],\n    \"partners\": [\n      \"NUP93\",\n      \"NUP188\",\n      \"YAP1\",\n      \"TAZ\",\n      \"TEAD1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"NUP205 is a scaffold nucleoporin of the inner ring (Nup93 sub-complex) of the nuclear pore complex, essential for NPC size-exclusion gating, long-term NPC maintenance, and regulated nuclear transport. It resides in the core NPC scaffold between the two coaxial rings, where it is reciprocally interdependent with NUP93 for NPC assembly; disease-causing mutations that disrupt NUP93 binding cause steroid-resistant nephrotic syndrome [PMID:26878725, PMID:15229283]. NUP205 participates in gene regulation by tethering the HOXA gene cluster at the nuclear periphery with NUP93/NUP188 to maintain a repressive chromatin state, and it mediates nuclear import of the Hippo pathway effectors YAP and TAZ, coupling NPC function to transcriptional signaling in podocytes [PMID:27980680, PMID:37565816]. At mitotic onset, NUP205 is removed from the nuclear envelope near centrosomes in an Aurora-A kinase–dependent manner, acting as a negative modulator of mitotic entry timing [PMID:22740626].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"The first functional characterization of Nup205 revealed that, beyond structural scaffolding, it is specifically required for the NPC's passive diffusion barrier — resolving whether individual inner-ring nucleoporins have discrete transport roles.\",\n      \"evidence\": \"RNAi depletion in C. elegans embryos with fluorescent size-exclusion and nuclear import assays\",\n      \"pmids\": [\"12937276\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which Nup205 establishes size exclusion not defined\", \"Vertebrate validation of size-exclusion role not performed\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Immunoelectron microscopy placed Nup205 at the core scaffold between the NPC's coaxial rings and RNAi showed it is dispensable for initial NPC assembly but required for long-term NPC maintenance, distinguishing its role from early-acting assembly factors.\",\n      \"evidence\": \"Postembedding immunoelectron microscopy and RNAi knockdown in HeLa cells\",\n      \"pmids\": [\"15229283\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural contacts with neighboring nucleoporins not resolved at molecular level\", \"Mechanism of NPC destabilization upon Nup205 loss not identified\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Discovery that Nup205 is selectively removed from the nuclear envelope near centrosomes at mitotic onset via Aurora-A kinase revealed an unexpected cell-cycle regulatory function — Nup205 negatively modulates mitotic entry timing.\",\n      \"evidence\": \"Live imaging, centrosome ablation/addition, Aurora-A inhibition, and RNAi modifier screen in C. elegans embryos\",\n      \"pmids\": [\"22740626\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct phosphorylation sites on Nup205 by Aurora-A not identified\", \"Whether this mitotic role is conserved in vertebrates not tested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"BioID proximity labeling in living human cells confirmed Nup205's spatial position within the Nup93 sub-complex at the inner ring, providing an in vivo interaction map complementing earlier EM data.\",\n      \"evidence\": \"BioID-mass spectrometry of NPC constituents in human cells\",\n      \"pmids\": [\"24927568\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Proximity does not prove direct binding; stoichiometry of interactions not resolved\", \"NUP205-specific contacts versus shared inner-ring contacts not distinguished\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Human genetic studies established NUP205 as a disease gene: mutations causing steroid-resistant nephrotic syndrome abrogate the NUP93–NUP205 interaction, and reciprocal knockdown demonstrated mutual dependence for NPC assembly, linking NPC structural integrity to podocyte function.\",\n      \"evidence\": \"Exome sequencing of SRNS families, co-immunoprecipitation, and NUP93 knockdown in podocytes\",\n      \"pmids\": [\"26878725\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which specific NPC transport pathways are disrupted in patient podocytes not defined\", \"Whether other organ phenotypes arise from NUP205 mutations not systematically assessed\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"A gene-regulatory role was established: NUP205, together with NUP93 and NUP188, associates with HOXA promoters and tethers the HOXA locus to the nuclear periphery to maintain a repressive chromatin state, showing inner-ring nucleoporins directly participate in transcriptional regulation.\",\n      \"evidence\": \"ChIP, 3D-FISH, histone modification analysis, and RNAi in DLD1 cells\",\n      \"pmids\": [\"27980680\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"NUP205's individual contribution versus NUP93's dominant role not cleanly separated\", \"Whether other genomic loci are similarly regulated is unknown\", \"Whether tethering requires NUP205's NPC-embedded state or occurs off-pore not determined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Unbiased interactomics in podocytes identified YAP and TAZ as NUP205 physical interactors and demonstrated that NUP205 is essential for their nuclear import and TEAD1-dependent transcriptional activity, connecting NPC function to Hippo signaling and providing a mechanistic link to the nephrotic syndrome phenotype.\",\n      \"evidence\": \"Label-free mass spectrometry interactome, NUP205 knockdown with nuclear/cytoplasmic fractionation, transcriptional reporter assays, and co-IP in podocytes\",\n      \"pmids\": [\"37565816\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether NUP205 acts as a direct transport receptor or facilitates FG-repeat-mediated translocation of YAP/TAZ not resolved\", \"TAZ-NUP205 feedback loop mechanism not fully characterized\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"In hepatocellular carcinoma, NUP205 was shown to stabilize YAP1 protein through the ubiquitin-proteasome pathway, extending its Hippo-pathway connection to an oncogenic context and demonstrating NUP205 influences YAP not only through nuclear import but also through protein turnover.\",\n      \"evidence\": \"NUP205 knockdown/overexpression, proteasome pathway assays, xenograft models, proliferation and apoptosis assays in HCC cells\",\n      \"pmids\": [\"41868261\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The E3 ubiquitin ligase involved in YAP1 destabilization upon NUP205 loss not identified\", \"Whether YAP1 stabilization is direct or mediated through an intermediary not established\", \"Single-lab finding awaiting independent replication\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: the structural basis of NUP205 within the human inner ring at atomic resolution, the direct phosphorylation events mediating its mitotic removal, and whether its selective transport and gene-regulatory functions operate through its NPC-embedded form or a soluble nucleoplasmic pool.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No high-resolution structure of human NUP205 in the NPC context\", \"Mechanism discriminating NPC-dependent versus NPC-independent functions not established\", \"Aurora-A phosphorylation sites on NUP205 not mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [1, 2, 3, 4]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0009607\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7, 8]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"Nup93 sub-complex (inner ring)\",\n      \"Nuclear pore complex (NPC)\"\n    ],\n    \"partners\": [\n      \"NUP93\",\n      \"NUP188\",\n      \"YAP1\",\n      \"TAZ\",\n      \"TEAD1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}