{"gene":"NUP160","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":2001,"finding":"NUP160 and NUP133 are novel vertebrate nucleoporins that form a complex (the Nup160 complex) with Nup107, Nup96, and Sec13 in Xenopus egg extracts and assembled pores. They are accessible on the basket side of the nuclear pore and were identified through pulldown experiments using Nup98 and Nup153 fragments. Specific Nup160 and Nup133 fragments block poly[A]+ RNA export but not protein import or export, establishing a direct role for NUP160 in mRNA export.","method":"Pulldown from Xenopus egg extracts, immunofluorescence, co-immunoprecipitation, in vivo transport assays with transfected fragments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (pulldown, co-IP, functional transport assay), replicated in Xenopus and mammalian cells","pmids":["11684705"],"is_preprint":false},{"year":2001,"finding":"Human Nup107 and Nup133 form a nuclear pore subcomplex that also contains Nup96 and a novel nucleoporin designated hNup120 (later referred to as Nup160). This Nup107-160 subcomplex localizes stably to both faces of the NPC at interphase and redistributes to kinetochores during mitosis, revealing a connection between NPC scaffold components and kinetochore function.","method":"Two-hybrid screens, immunoprecipitation, immunofluorescence, photobleaching (FRAP)","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP, yeast two-hybrid, direct localization imaging in multiple cell contexts; replicated across labs","pmids":["11564755"],"is_preprint":false},{"year":2004,"finding":"The entire Nup107-160 complex, including NUP160 and three newly identified members (Nup37, Nup43, Seh1), is targeted as one entity to kinetochores from prophase to anaphase during mitosis. Depletion of individual members by RNAi phenocopies each other, indicating functional interdependence within the complex.","method":"GFP-tagging, immunofluorescence with specific antibodies, RNA interference knockdown, biochemical fractionation","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal approaches (imaging, RNAi phenotype, biochemistry), replicated findings on complex composition","pmids":["15146057"],"is_preprint":false},{"year":2013,"finding":"Electron tomography, single-particle EM, and crosslinking mass spectrometry show that 32 copies of the Nup107 subcomplex (which includes NUP160) assemble into two reticulated rings at the cytoplasmic and nuclear faces of the human NPC, defining how the scaffold accommodates large cargo transport.","method":"Electron tomography, single-particle electron microscopy, crosslinking mass spectrometry","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 — integrated structural analysis with multiple high-resolution methods","pmids":["24315095"],"is_preprint":false},{"year":2014,"finding":"BioID proximity-dependent biotinylation applied to constituents of the Nup107-160 complex (including NUP160) in living human cells defined the spatial organization of the NPC subcomplex and demonstrated a direct interaction of Nup43 with Nup85 within the extremely stable Nup107-160 structure, using NUP160-BioID fusions as a molecular ruler to define the labeling radius.","method":"Proximity-dependent biotin identification (BioID), mass spectrometry","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo proximity labeling with functional inference, single study","pmids":["24927568"],"is_preprint":false},{"year":2015,"finding":"The NUP160-SLC43A3 fusion oncogene, arising from NUP160 truncation, is expressed in a subset of human angiosarcomas. Stable expression of the fusion in endothelial cells increases cell proliferation and induces an angiosarcoma-like gene expression pattern; subcutaneous implantation of fusion-expressing fibroblasts produces angiosarcoma-like tumors in vivo, implicating NUP160 truncation as oncogenic.","method":"Transcriptome sequencing, stable cell line expression, RNAi knockdown, xenograft tumor assay","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 — multiple functional assays (in vitro and in vivo), single study","pmids":["26527604"],"is_preprint":false},{"year":2015,"finding":"Drosophila Nup160 (D. simulans allele) interacts genetically with Nup96 and additional autosomal factors to cause hybrid lethality in crosses with D. melanogaster; population genetic analysis reveals recurrent positive selection at Nup160 before and after speciation of the D. simulans clade, consistent with NUP160 evolving rapidly under natural selection at the species interface.","method":"Genetic crosses, introgression lines, population genetics analysis, complementation tests","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis dissected in multiple cross configurations, single lab","pmids":["26022241"],"is_preprint":false},{"year":2019,"finding":"Compound-heterozygous mutations in NUP160 cause steroid-resistant nephrotic syndrome (SRNS). In a Drosophila nephrocyte model, silencing of Nup160 caused functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure; these defects were rescued by wild-type human NUP160 but not by one of the disease-associated mutant alleles, establishing NUP160 mutations as causative for SRNS.","method":"Whole-exome/Sanger sequencing, Drosophila nephrocyte RNAi model, rescue experiments with wild-type and mutant human NUP160","journal":"Journal of the American Society of Nephrology : JASN","confidence":"High","confidence_rationale":"Tier 2 — genetic loss-of-function with specific phenotype, rescued by human wild-type but not mutant allele, orthogonal validation","pmids":["30910934"],"is_preprint":false},{"year":2018,"finding":"Knockdown of NUP160 in mouse podocytes inhibits cell proliferation by decreasing cyclin D1 and CDK4 expression, increasing p27, and inducing S-phase arrest. It also promotes apoptosis, autophagy, and cell migration, and decreases expression and alters subcellular localization of slit-diaphragm proteins nephrin, podocin, and CD2AP while increasing α-actinin-4.","method":"shRNA knockdown in immortalized mouse podocytes, flow cytometry, Western blot, immunofluorescence","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2–3 — clean KD with defined cellular and molecular phenotypes, single lab","pmids":["29704630"],"is_preprint":false},{"year":2024,"finding":"Podocyte-specific Nup160 knockout (Nup160podKO) mice generated by CRISPR/Cas9 and Cre/loxP develop progressive proteinuria and glomerulosclerosis, recapitulating the nephrotic syndrome phenotype of human NUP160 mutations and establishing NUP160 as causally required for podocyte integrity in a mammalian model.","method":"CRISPR/Cas9 and Cre/loxP conditional knockout mouse model, urine ACR measurement, serum albumin, histology","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — conditional mammalian KO with specific quantitative phenotype, strong causal evidence","pmids":["38224683"],"is_preprint":false},{"year":2025,"finding":"Loss of Nup160 in podocyte-specific knockout mice decreases CDC42 protein levels and activity (despite elevated CDC42 mRNA), causing progressive proteinuria and foot-process fusion. This post-transcriptional dysregulation of CDC42 parallels findings from knockout of other outer-ring NPC components (NUP85, NUP107, NUP133), implicating CDC42 downregulation as a shared mechanism in NUP160-associated SRNS.","method":"CRISPR/Cas9 Cre/loxP knockout mouse with dual-fluorescent reporter, single-cell transcriptomics, proteomics of primary podocytes, CDC42 activity assay","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 1–2 — multi-omic approach (transcriptome + proteome + activity assay) in conditional KO model with clear molecular mechanism","pmids":["40298220"],"is_preprint":false},{"year":2021,"finding":"NUP160 knockdown in high-glucose-treated kidney tubular cells and STZ-induced diabetic nephropathy mice restores autophagic flux (increased LC3II/LC3I ratio, decreased p62) and inhibits NF-κB signaling, inflammation, and fibrosis, suggesting NUP160 negatively regulates autophagy in the diabetic kidney context.","method":"shRNA knockdown in NRK-52E cells, STZ mouse model, Western blot, immunofluorescence, histological staining","journal":"Bioengineered","confidence":"Medium","confidence_rationale":"Tier 2–3 — in vitro and in vivo KD with molecular pathway readout (LC3, p62, NF-κB), single lab","pmids":["34533106"],"is_preprint":false},{"year":2019,"finding":"MicroRNA-577 directly targets NUP160 mRNA (validated by dual-luciferase reporter assay); up-regulation of miR-577 reduces NUP160 expression in CML cells, inhibits cell proliferation and cycle progression, and enhances imatinib sensitivity, placing NUP160 downstream of miR-577 in CML drug resistance.","method":"qRT-PCR, dual-luciferase reporter assay, CCK-8 proliferation assay, flow cytometry, cell reverse experiment","journal":"European review for medical and pharmacological sciences","confidence":"Medium","confidence_rationale":"Tier 3 — direct miRNA-target validation by luciferase assay, functional rescue in cell lines, single lab","pmids":["31486501"],"is_preprint":false},{"year":2022,"finding":"lncRNA HCG18 upregulates NUP160 by sponging miR-495-3p (a ceRNA mechanism); miR-495-3p directly targets NUP160 (confirmed by luciferase reporter). NUP160 overexpression reverses the protective effects of HCG18 knockdown in high-glucose-treated podocytes, placing NUP160 as a downstream effector in the HCG18/miR-495-3p axis regulating podocyte apoptosis and inflammation.","method":"Luciferase reporter assay, Western blot, RT-qPCR, flow cytometry, ELISA, in vivo STZ rat model","journal":"Regenerative therapy","confidence":"Medium","confidence_rationale":"Tier 3 — direct miRNA-target validation, ceRNA mechanism via luciferase and rescue experiments, single lab","pmids":["35785044"],"is_preprint":false}],"current_model":"NUP160 is a core scaffold nucleoporin of the evolutionarily conserved Nup107-160 outer-ring subcomplex of the nuclear pore complex; it forms a stable complex with Nup107, Nup133, Nup96, Sec13, Nup37, Nup43, and Seh1, is required for mRNA export but not protein import/export, and redistributes to kinetochores during mitosis; loss of NUP160 in podocytes post-transcriptionally reduces CDC42 protein levels and activity, disrupting the cytoskeletal architecture required for glomerular filtration and causing steroid-resistant nephrotic syndrome, while NUP160 expression is additionally regulated by miR-577 and the HCG18/miR-495-3p ceRNA axis in disease contexts."},"narrative":{"teleology":[{"year":2001,"claim":"Identification of NUP160 as a novel vertebrate nucleoporin within a defined NPC subcomplex (with Nup107, Nup133, Nup96, Sec13) resolved the composition of a major outer-ring module and established that NUP160 fragments selectively block mRNA export without affecting protein transport.","evidence":"Pulldown from Xenopus egg extracts, co-IP, immunofluorescence, in vivo transport assays in mammalian cells; independently, yeast two-hybrid and reciprocal co-IP in human cells","pmids":["11684705","11564755"],"confidence":"High","gaps":["Precise contact surfaces between NUP160 and other subcomplex members not mapped","Mechanism by which NUP160 selectively facilitates mRNA but not protein export unresolved"]},{"year":2004,"claim":"Demonstration that the entire Nup107-160 complex (now including Nup37, Nup43, Seh1) relocates as a unit to kinetochores during mitosis, with individual subunit depletions phenocopying each other, established functional interdependence and a dual interphase/mitotic role for NUP160.","evidence":"GFP-tagging, immunofluorescence, RNAi knockdown, biochemical fractionation in human cells","pmids":["15146057"],"confidence":"High","gaps":["Direct contribution of NUP160 to kinetochore function versus passive co-recruitment not distinguished","Whether mitotic targeting requires NUP160 specifically or any intact subcomplex member unknown"]},{"year":2013,"claim":"High-resolution structural analysis revealed that 32 copies of the Nup107 subcomplex assemble into two reticulated rings at the NPC, defining the stoichiometry and spatial arrangement of NUP160 within the intact human pore scaffold.","evidence":"Electron tomography, single-particle EM, crosslinking mass spectrometry of human NPCs","pmids":["24315095"],"confidence":"High","gaps":["Atomic-resolution contacts of NUP160 within the ring not resolved","Conformational dynamics of NUP160 during cargo translocation unknown"]},{"year":2014,"claim":"BioID proximity labeling using NUP160 fusions as a molecular ruler mapped in vivo spatial relationships within the Nup107-160 complex, confirming its extreme stability and delineating subunit proximity in living cells.","evidence":"BioID proximity biotinylation with mass spectrometry in HEK293 cells","pmids":["24927568"],"confidence":"Medium","gaps":["Proximity data do not distinguish direct from indirect contacts","Single study without orthogonal structural validation of the inferred distances"]},{"year":2015,"claim":"Discovery of the NUP160-SLC43A3 fusion oncogene in angiosarcomas and its ability to drive endothelial proliferation and tumor formation in vivo revealed that truncation of NUP160 can be oncogenic, raising the question of whether NPC scaffold disruption contributes to tumorigenesis.","evidence":"Transcriptome sequencing of angiosarcomas, stable cell line expression, xenograft tumor assay","pmids":["26527604"],"confidence":"Medium","gaps":["Which domains of NUP160 are required for oncogenic activity not determined","Whether the fusion alters NPC-dependent transport or acts through a gain-of-function mechanism unknown"]},{"year":2015,"claim":"Genetic analysis in Drosophila showed that Nup160 interacts epistatically with Nup96 to cause hybrid lethality and evolves under recurrent positive selection, linking NPC outer-ring components to speciation barriers.","evidence":"Genetic crosses, introgression lines, population genetics in D. simulans/D. melanogaster","pmids":["26022241"],"confidence":"Medium","gaps":["Molecular basis of Nup160-Nup96 hybrid incompatibility not identified","Whether the rapid evolution affects NPC transport function or another activity unclear"]},{"year":2019,"claim":"Identification of compound-heterozygous NUP160 mutations in steroid-resistant nephrotic syndrome patients, with functional validation showing that wild-type but not mutant NUP160 rescues nephrocyte defects in Drosophila, established NUP160 as a causative SRNS gene.","evidence":"Whole-exome sequencing, Drosophila nephrocyte RNAi with human NUP160 rescue","pmids":["30910934"],"confidence":"High","gaps":["How specific NUP160 mutations impair NPC function at the molecular level unknown","Whether SRNS-associated mutations affect mRNA export, CDC42 regulation, or both not resolved"]},{"year":2018,"claim":"Knockdown of NUP160 in mouse podocytes revealed downstream cell-cycle arrest, apoptosis, autophagy induction, and mislocalization of slit-diaphragm proteins, establishing that NUP160 loss has broad effects on podocyte homeostasis beyond NPC function.","evidence":"shRNA knockdown in immortalized mouse podocytes, flow cytometry, Western blot, immunofluorescence","pmids":["29704630"],"confidence":"Medium","gaps":["Whether effects on slit-diaphragm proteins are direct or secondary to NPC dysfunction not distinguished","Single cell-line study without in vivo validation at the time"]},{"year":2024,"claim":"Generation of podocyte-specific Nup160 knockout mice confirmed the causal role of NUP160 in glomerular disease by recapitulating progressive proteinuria and glomerulosclerosis in a mammalian model, bridging human genetics and Drosophila studies.","evidence":"CRISPR/Cas9 and Cre/loxP conditional knockout mouse, histology, urine ACR, serum albumin","pmids":["38224683"],"confidence":"High","gaps":["Temporal requirement for NUP160 in mature versus developing podocytes not defined","Whether the phenotype is fully cell-autonomous or involves paracrine effects not tested"]},{"year":2025,"claim":"Multi-omic profiling of Nup160-knockout podocytes revealed that NUP160 loss post-transcriptionally decreases CDC42 protein and activity despite elevated CDC42 mRNA, identifying a shared mechanism with other outer-ring nucleoporin knockouts (NUP85, NUP107, NUP133) and linking NPC scaffold integrity to Rho GTPase-dependent cytoskeletal regulation.","evidence":"Conditional KO mouse, dual-fluorescent reporter, single-cell transcriptomics, proteomics, CDC42 activity assay","pmids":["40298220"],"confidence":"High","gaps":["Mechanism of post-transcriptional CDC42 downregulation (translation, stability, or export defect) not determined","Whether restoring CDC42 activity is sufficient to rescue the podocyte phenotype not tested"]},{"year":null,"claim":"The precise molecular mechanism by which NUP160 (and the Nup107-160 complex) post-transcriptionally controls CDC42 levels in podocytes remains to be determined — whether through selective mRNA export, translational regulation, or protein stability — and whether this mechanism operates in non-podocyte contexts is unknown.","evidence":"","pmids":[],"confidence":"High","gaps":["No reconstitution of the CDC42 regulatory mechanism in vitro","Atomic-resolution structure of NUP160 within the intact human NPC not available","Whether NUP160's role in mRNA export and its CDC42-regulatory function are mechanistically linked is unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,2,3]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,1,3,4]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,2]}],"complexes":["Nup107-160 complex (Y-complex / outer ring complex)","Nuclear pore complex"],"partners":["NUP107","NUP133","NUP96","SEC13","NUP37","NUP43","SEH1L","CDC42"],"other_free_text":[]},"mechanistic_narrative":"NUP160 is a core scaffold nucleoporin of the Nup107-160 outer-ring subcomplex of the nuclear pore complex, essential for NPC architecture, mRNA export, and kinetochore targeting during mitosis. It forms a stable complex with Nup107, Nup133, Nup96, Sec13, Nup37, Nup43, and Seh1, with 32 copies of this subcomplex assembling into two reticulated rings at the cytoplasmic and nuclear faces of the NPC [PMID:11684705, PMID:11564755, PMID:24315095]. NUP160 is required for poly(A)+ RNA export but dispensable for protein import/export, and its loss in podocytes post-transcriptionally reduces CDC42 protein levels and activity, disrupting cytoskeletal architecture and glomerular filtration [PMID:11684705, PMID:40298220]. Compound-heterozygous mutations in NUP160 cause steroid-resistant nephrotic syndrome, validated by rescue experiments in Drosophila nephrocytes and recapitulated in podocyte-specific knockout mice [PMID:30910934, PMID:38224683]."},"prefetch_data":{"uniprot":{"accession":"Q12769","full_name":"Nuclear pore complex protein Nup160","aliases":["160 kDa nucleoporin","Nucleoporin Nup160"],"length_aa":1436,"mass_kda":162.1,"function":"Functions as a component of the nuclear pore complex (NPC) (PubMed:11564755, PubMed:11684705). Involved in poly(A)+ RNA transport","subcellular_location":"Nucleus, nuclear pore complex","url":"https://www.uniprot.org/uniprotkb/Q12769/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP160","classification":"Common Essential","n_dependent_lines":1133,"n_total_lines":1208,"dependency_fraction":0.9379139072847682},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"FKBP5","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2},{"gene":"SEC13","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP160","total_profiled":1310},"omim":[{"mim_id":"618348","title":"GALLOWAY-MOWAT SYNDROME 7; GAMOS7","url":"https://www.omim.org/entry/618348"},{"mim_id":"618178","title":"NEPHROTIC SYNDROME, TYPE 19; NPHS19","url":"https://www.omim.org/entry/618178"},{"mim_id":"618176","title":"NEPHROTIC SYNDROME, TYPE 17; NPHS17","url":"https://www.omim.org/entry/618176"},{"mim_id":"615753","title":"POM121 TRANSMEMBRANE NUCLEOPORIN; POM121","url":"https://www.omim.org/entry/615753"},{"mim_id":"610853","title":"AT-HOOK-CONTAINING TRANSCRIPTION FACTOR 1; AHCTF1","url":"https://www.omim.org/entry/610853"}],"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/NUP160"},"hgnc":{"alias_symbol":["KIAA0197","FLJ22583"],"prev_symbol":[]},"alphafold":{"accession":"Q12769","domains":[{"cath_id":"-","chopping":"1212-1333","consensus_level":"medium","plddt":82.9312,"start":1212,"end":1333},{"cath_id":"1.20.58","chopping":"1335-1436","consensus_level":"medium","plddt":79.3018,"start":1335,"end":1436}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q12769","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q12769-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q12769-F1-predicted_aligned_error_v6.png","plddt_mean":80.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP160","jax_strain_url":"https://www.jax.org/strain/search?query=NUP160"},"sequence":{"accession":"Q12769","fasta_url":"https://rest.uniprot.org/uniprotkb/Q12769.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q12769/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q12769"}},"corpus_meta":[{"pmid":"11684705","id":"PMC_11684705","title":"Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export.","date":"2001","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11684705","citation_count":153,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26527604","id":"PMC_26527604","title":"NUP160-SLC43A3 is a novel recurrent fusion oncogene in angiosarcoma.","date":"2015","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/26527604","citation_count":44,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30910934","id":"PMC_30910934","title":"Mutations in NUP160 Are Implicated in Steroid-Resistant Nephrotic Syndrome.","date":"2019","source":"Journal of the American Society of Nephrology : JASN","url":"https://pubmed.ncbi.nlm.nih.gov/30910934","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22902705","id":"PMC_22902705","title":"Nucleoporins Nup160 and Seh1 are required for disease resistance in 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communications","url":"https://pubmed.ncbi.nlm.nih.gov/27173435","citation_count":211,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10709,"output_tokens":3028,"usd":0.038774},"stage2":{"model":"claude-opus-4-6","input_tokens":6384,"output_tokens":2353,"usd":0.136118},"total_usd":0.391365,"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":22216,"output_tokens":3531,"usd":0.059806},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":7169,"output_tokens":2744,"usd":0.156667}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"Nup160 and Nup133 are novel vertebrate nucleoporins that form a complex with Nup107, Nup96, and Sec13 (the Nup160 complex) in Xenopus egg extracts and in assembled pores. Nup160 is accessible on the basket side of the nuclear pore and is required for mRNA export but not protein import or export, as demonstrated by pulldown from Xenopus egg extracts, co-immunoprecipitation, and in vivo transport assays using transfected Nup160/Nup133 fragments that block poly[A]+ RNA export.\",\n      \"method\": \"Pulldown from Xenopus egg extracts, co-immunoprecipitation, immunofluorescence, transfection with in vivo transport assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal pulldowns, complex reconstitution from egg extracts, functional transport assay, replicated across multiple approaches in a single study\",\n      \"pmids\": [\"11684705\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In Drosophila, Nup160 genetically interacts with Nup96 to cause hybrid lethality in interspecies crosses; null mutations of Nup160 phenocopy the hybrid inviability, female sterility, and morphological anomalies caused by the D. simulans Nup160 allele, establishing Nup160's role in developmental viability and placing it in a genetic pathway with Nup96.\",\n      \"method\": \"Transposon excision genetics, null mutation analysis, introgression lines, population genetics\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — epistasis by genetic dissection, replicated across multiple alleles, but no biochemical mechanism resolved\",\n      \"pmids\": [\"26022241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Null mutations in Drosophila melanogaster Nup160 (by transposon excision) result in hybrid inviability, female sterility, and morphological anomalies, confirming that Nup160 loss-of-function causes these phenotypes and establishing the lethal phase as early pupal stage.\",\n      \"method\": \"Transposon excision, null mutation complementation, genetic analysis\",\n      \"journal\": \"Genes & genetic systems\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean genetic loss-of-function with defined phenotypic readouts, consistent with ortholog function\",\n      \"pmids\": [\"22820383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Knockdown of NUP160 in mouse podocytes inhibits cell proliferation by decreasing cyclin D1 and CDK4 expression, increasing p27 expression, and inducing S-phase arrest; it also promotes apoptosis and autophagy, enhances cell migration, and alters the expression and subcellular localization of podocyte-associated molecules nephrin, podocin, CD2AP, and α-actinin-4.\",\n      \"method\": \"shRNA knockdown, flow cytometry, Western blot, immunofluorescence in conditionally immortalized mouse podocytes\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with multiple defined cellular phenotypes and mechanistic markers, single lab\",\n      \"pmids\": [\"29704630\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"microRNA-577 directly targets the 3'UTR of NUP160 (validated by dual-luciferase reporter assay), and upregulation of miR-577 reduces NUP160 expression in CML cells, thereby promoting sensitivity to imatinib.\",\n      \"method\": \"Dual-luciferase reporter gene assay, qRT-PCR, CCK-8 proliferation assay, flow cytometry\",\n      \"journal\": \"European review for medical and pharmacological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — luciferase reporter validates direct miRNA-NUP160 interaction; single lab, moderate follow-up\",\n      \"pmids\": [\"31486501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Silencing of Drosophila NUP160 specifically in nephrocytes leads to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure; these defects are completely rescued by wild-type human NUP160 but not by a pathogenic NUP160 mutant allele, establishing Nup160's role in nuclear pore complex integrity and nuclear architecture in renal cells.\",\n      \"method\": \"RNAi in Drosophila nephrocytes, rescue with human wild-type vs. mutant NUP160, functional nephrocyte assay, microscopy\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vivo loss-of-function with species-swap rescue, multiple orthogonal phenotypic readouts, allele-specific functional differentiation\",\n      \"pmids\": [\"30910934\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Podocyte-specific knockout of Nup160 in mice (using CRISPR/Cas9 and Cre/loxP) results in progressive proteinuria, reduced serum albumin, and glomerulosclerosis, establishing that NUP160 loss-of-function in podocytes is sufficient to cause nephrotic syndrome in a mammalian model.\",\n      \"method\": \"CRISPR/Cas9 and Cre/loxP conditional knockout mouse model, urinary albumin/creatinine ratio, serum albumin, histopathology\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean conditional KO with multiple defined disease phenotypes in mammalian model\",\n      \"pmids\": [\"38224683\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of Nup160 in podocyte-specific knockout mice decreases Cdc42 protein levels and reduces Cdc42 activity in primary podocytes (despite elevated Cdc42 mRNA), placing NUP160 upstream of CDC42 regulation and suggesting post-transcriptional control of CDC42 as a mechanism contributing to SRNS pathogenesis.\",\n      \"method\": \"Single-cell transcriptomics, proteomics of glomerular cells, Western blot, Cdc42 activity assay in primary podocytes from conditional KO mice\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — proteomic and transcriptomic dissociation establishes post-transcriptional mechanism; single lab, novel finding\",\n      \"pmids\": [\"40298220\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"lncRNA HCG18 upregulates NUP160 by sponging miR-495-3p (which directly targets NUP160), establishing an HCG18/miR-495-3p/NUP160 ceRNA regulatory axis in podocytes under high glucose conditions; NUP160 overexpression reverses the protective effects of HCG18 knockdown.\",\n      \"method\": \"Luciferase reporter assay, Western blot, RT-qPCR, flow cytometry in podocytes\",\n      \"journal\": \"Regenerative therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — luciferase reporter validates miR-495-3p/NUP160 interaction; ceRNA mechanism supported by rescue experiment; single lab\",\n      \"pmids\": [\"35785044\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"IGF2BP2, an m6A reader protein, directly interacts with NUP160 mRNA (via its KH3-4 domain) to stabilize it, placing NUP160 downstream of the circRAPGEF5/IGF2BP2 axis; genetic ablation of NUP160 by RNAi restores autophagic flux and attenuates aggressive behaviors of lung adenocarcinoma cells, establishing NUP160 as a suppressor of autophagy in this context.\",\n      \"method\": \"RNA pulldown, mass spectrometry, RNA immunoprecipitation, m6A-RIP-PCR, mRFP-GFP-LC3 autophagic flux assay, xenograft mouse model\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — RNA pulldown/MS identifies IGF2BP2-NUP160 mRNA interaction; functional autophagy assay; in vivo validation; single lab\",\n      \"pmids\": [\"40629330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Knockdown of NUP160 in high-glucose-treated kidney tubular cells and STZ-induced diabetic nephropathy mice restores autophagy (increased LC3II/I ratio, decreased p62) and inhibits inflammation and fibrosis by inactivating NF-κB signaling, establishing a functional link between NUP160 and autophagy regulation via the NF-κB pathway.\",\n      \"method\": \"siRNA knockdown, Western blot, immunofluorescence, H&E/Masson/PAS staining in vivo, STZ mouse model\",\n      \"journal\": \"Bioengineered\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with defined molecular markers of autophagy and NF-κB, in vitro and in vivo; single lab\",\n      \"pmids\": [\"34533106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NUP160 knockdown in podocytes affects autophagy through activation of the JAK2/STAT3 signaling pathway, as shown by increased p-JAK2/JAK2 and p-STAT3/STAT3 ratios and altered LC3B-II/I and p62 levels upon NUP160 silencing under high glucose conditions.\",\n      \"method\": \"siRNA knockdown, Western blot for JAK2/STAT3 phosphorylation, LC3B, p62, flow cytometry for apoptosis\",\n      \"journal\": \"Iranian journal of kidney diseases\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single method set, no direct demonstration of JAK2/STAT3 as direct NUP160 targets\",\n      \"pmids\": [\"38043110\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP160 is an outer-ring nucleoporin that assembles into the Nup107-160 subcomplex (with Nup133, Nup107, Nup96, and Sec13) at the nuclear pore complex basket, where it is required for mRNA export; in podocytes, NUP160 loss disrupts nuclear pore integrity, reduces CDC42 protein levels and activity post-transcriptionally, and impairs expression and localization of slit-diaphragm molecules, causing nephrotic syndrome in mice; additionally, NUP160 mRNA is stabilized by the IGF2BP2/circRAPGEF5 axis and functions as a suppressor of autophagy in cancer cells.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"NUP160 and NUP133 are novel vertebrate nucleoporins that form a complex (the Nup160 complex) with Nup107, Nup96, and Sec13 in Xenopus egg extracts and assembled pores. They are accessible on the basket side of the nuclear pore and were identified through pulldown experiments using Nup98 and Nup153 fragments. Specific Nup160 and Nup133 fragments block poly[A]+ RNA export but not protein import or export, establishing a direct role for NUP160 in mRNA export.\",\n      \"method\": \"Pulldown from Xenopus egg extracts, immunofluorescence, co-immunoprecipitation, in vivo transport assays with transfected fragments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (pulldown, co-IP, functional transport assay), replicated in Xenopus and mammalian cells\",\n      \"pmids\": [\"11684705\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Human Nup107 and Nup133 form a nuclear pore subcomplex that also contains Nup96 and a novel nucleoporin designated hNup120 (later referred to as Nup160). This Nup107-160 subcomplex localizes stably to both faces of the NPC at interphase and redistributes to kinetochores during mitosis, revealing a connection between NPC scaffold components and kinetochore function.\",\n      \"method\": \"Two-hybrid screens, immunoprecipitation, immunofluorescence, photobleaching (FRAP)\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP, yeast two-hybrid, direct localization imaging in multiple cell contexts; replicated across labs\",\n      \"pmids\": [\"11564755\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The entire Nup107-160 complex, including NUP160 and three newly identified members (Nup37, Nup43, Seh1), is targeted as one entity to kinetochores from prophase to anaphase during mitosis. Depletion of individual members by RNAi phenocopies each other, indicating functional interdependence within the complex.\",\n      \"method\": \"GFP-tagging, immunofluorescence with specific antibodies, RNA interference knockdown, biochemical fractionation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal approaches (imaging, RNAi phenotype, biochemistry), replicated findings on complex composition\",\n      \"pmids\": [\"15146057\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Electron tomography, single-particle EM, and crosslinking mass spectrometry show that 32 copies of the Nup107 subcomplex (which includes NUP160) assemble into two reticulated rings at the cytoplasmic and nuclear faces of the human NPC, defining how the scaffold accommodates large cargo transport.\",\n      \"method\": \"Electron tomography, single-particle electron microscopy, crosslinking mass spectrometry\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — integrated structural analysis with multiple high-resolution methods\",\n      \"pmids\": [\"24315095\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"BioID proximity-dependent biotinylation applied to constituents of the Nup107-160 complex (including NUP160) in living human cells defined the spatial organization of the NPC subcomplex and demonstrated a direct interaction of Nup43 with Nup85 within the extremely stable Nup107-160 structure, using NUP160-BioID fusions as a molecular ruler to define the labeling radius.\",\n      \"method\": \"Proximity-dependent biotin identification (BioID), 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 — in vivo proximity labeling with functional inference, single study\",\n      \"pmids\": [\"24927568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The NUP160-SLC43A3 fusion oncogene, arising from NUP160 truncation, is expressed in a subset of human angiosarcomas. Stable expression of the fusion in endothelial cells increases cell proliferation and induces an angiosarcoma-like gene expression pattern; subcutaneous implantation of fusion-expressing fibroblasts produces angiosarcoma-like tumors in vivo, implicating NUP160 truncation as oncogenic.\",\n      \"method\": \"Transcriptome sequencing, stable cell line expression, RNAi knockdown, xenograft tumor assay\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple functional assays (in vitro and in vivo), single study\",\n      \"pmids\": [\"26527604\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Drosophila Nup160 (D. simulans allele) interacts genetically with Nup96 and additional autosomal factors to cause hybrid lethality in crosses with D. melanogaster; population genetic analysis reveals recurrent positive selection at Nup160 before and after speciation of the D. simulans clade, consistent with NUP160 evolving rapidly under natural selection at the species interface.\",\n      \"method\": \"Genetic crosses, introgression lines, population genetics analysis, complementation tests\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis dissected in multiple cross configurations, single lab\",\n      \"pmids\": [\"26022241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Compound-heterozygous mutations in NUP160 cause steroid-resistant nephrotic syndrome (SRNS). In a Drosophila nephrocyte model, silencing of Nup160 caused functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure; these defects were rescued by wild-type human NUP160 but not by one of the disease-associated mutant alleles, establishing NUP160 mutations as causative for SRNS.\",\n      \"method\": \"Whole-exome/Sanger sequencing, Drosophila nephrocyte RNAi model, rescue experiments with wild-type and mutant human NUP160\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function with specific phenotype, rescued by human wild-type but not mutant allele, orthogonal validation\",\n      \"pmids\": [\"30910934\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Knockdown of NUP160 in mouse podocytes inhibits cell proliferation by decreasing cyclin D1 and CDK4 expression, increasing p27, and inducing S-phase arrest. It also promotes apoptosis, autophagy, and cell migration, and decreases expression and alters subcellular localization of slit-diaphragm proteins nephrin, podocin, and CD2AP while increasing α-actinin-4.\",\n      \"method\": \"shRNA knockdown in immortalized mouse podocytes, flow cytometry, Western blot, immunofluorescence\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — clean KD with defined cellular and molecular phenotypes, single lab\",\n      \"pmids\": [\"29704630\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Podocyte-specific Nup160 knockout (Nup160podKO) mice generated by CRISPR/Cas9 and Cre/loxP develop progressive proteinuria and glomerulosclerosis, recapitulating the nephrotic syndrome phenotype of human NUP160 mutations and establishing NUP160 as causally required for podocyte integrity in a mammalian model.\",\n      \"method\": \"CRISPR/Cas9 and Cre/loxP conditional knockout mouse model, urine ACR measurement, serum albumin, histology\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — conditional mammalian KO with specific quantitative phenotype, strong causal evidence\",\n      \"pmids\": [\"38224683\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of Nup160 in podocyte-specific knockout mice decreases CDC42 protein levels and activity (despite elevated CDC42 mRNA), causing progressive proteinuria and foot-process fusion. This post-transcriptional dysregulation of CDC42 parallels findings from knockout of other outer-ring NPC components (NUP85, NUP107, NUP133), implicating CDC42 downregulation as a shared mechanism in NUP160-associated SRNS.\",\n      \"method\": \"CRISPR/Cas9 Cre/loxP knockout mouse with dual-fluorescent reporter, single-cell transcriptomics, proteomics of primary podocytes, CDC42 activity assay\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multi-omic approach (transcriptome + proteome + activity assay) in conditional KO model with clear molecular mechanism\",\n      \"pmids\": [\"40298220\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NUP160 knockdown in high-glucose-treated kidney tubular cells and STZ-induced diabetic nephropathy mice restores autophagic flux (increased LC3II/LC3I ratio, decreased p62) and inhibits NF-κB signaling, inflammation, and fibrosis, suggesting NUP160 negatively regulates autophagy in the diabetic kidney context.\",\n      \"method\": \"shRNA knockdown in NRK-52E cells, STZ mouse model, Western blot, immunofluorescence, histological staining\",\n      \"journal\": \"Bioengineered\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — in vitro and in vivo KD with molecular pathway readout (LC3, p62, NF-κB), single lab\",\n      \"pmids\": [\"34533106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MicroRNA-577 directly targets NUP160 mRNA (validated by dual-luciferase reporter assay); up-regulation of miR-577 reduces NUP160 expression in CML cells, inhibits cell proliferation and cycle progression, and enhances imatinib sensitivity, placing NUP160 downstream of miR-577 in CML drug resistance.\",\n      \"method\": \"qRT-PCR, dual-luciferase reporter assay, CCK-8 proliferation assay, flow cytometry, cell reverse experiment\",\n      \"journal\": \"European review for medical and pharmacological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct miRNA-target validation by luciferase assay, functional rescue in cell lines, single lab\",\n      \"pmids\": [\"31486501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"lncRNA HCG18 upregulates NUP160 by sponging miR-495-3p (a ceRNA mechanism); miR-495-3p directly targets NUP160 (confirmed by luciferase reporter). NUP160 overexpression reverses the protective effects of HCG18 knockdown in high-glucose-treated podocytes, placing NUP160 as a downstream effector in the HCG18/miR-495-3p axis regulating podocyte apoptosis and inflammation.\",\n      \"method\": \"Luciferase reporter assay, Western blot, RT-qPCR, flow cytometry, ELISA, in vivo STZ rat model\",\n      \"journal\": \"Regenerative therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct miRNA-target validation, ceRNA mechanism via luciferase and rescue experiments, single lab\",\n      \"pmids\": [\"35785044\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP160 is a core scaffold nucleoporin of the evolutionarily conserved Nup107-160 outer-ring subcomplex of the nuclear pore complex; it forms a stable complex with Nup107, Nup133, Nup96, Sec13, Nup37, Nup43, and Seh1, is required for mRNA export but not protein import/export, and redistributes to kinetochores during mitosis; loss of NUP160 in podocytes post-transcriptionally reduces CDC42 protein levels and activity, disrupting the cytoskeletal architecture required for glomerular filtration and causing steroid-resistant nephrotic syndrome, while NUP160 expression is additionally regulated by miR-577 and the HCG18/miR-495-3p ceRNA axis in disease contexts.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP160 is an outer-ring nucleoporin that functions as a core component of the Nup107-160 subcomplex at the nuclear pore, where it is required for mRNA export and maintenance of nuclear envelope architecture. NUP160 assembles with Nup133, Nup107, Nup96, and Sec13 and localizes to the basket side of the nuclear pore; it is selectively required for poly(A)+ RNA export but dispensable for protein import and export [PMID:11684705]. In podocytes, NUP160 loss disrupts nuclear pore integrity and causes nephrotic syndrome in conditional knockout mice, with downstream post-transcriptional reduction of CDC42 protein and activity, altered slit-diaphragm molecule expression, and deregulated autophagy via NF-κB signaling [PMID:38224683, PMID:40298220, PMID:34533106]. NUP160 mRNA is stabilized by the m6A reader IGF2BP2 and acts as a suppressor of autophagic flux in lung adenocarcinoma cells, linking nucleoporin abundance to autophagy regulation and tumor progression [PMID:40629330].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"The identity and immediate function of NUP160 were established: it is a novel vertebrate nucleoporin that forms a discrete subcomplex with Nup133, Nup107, Nup96, and Sec13, localizes to the basket side of the pore, and is selectively required for mRNA export but not protein transport.\",\n      \"evidence\": \"Pulldown from Xenopus egg extracts, co-immunoprecipitation, immunofluorescence, and in vivo transport assays with dominant-negative fragments\",\n      \"pmids\": [\"11684705\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural detail on how NUP160 contacts its subcomplex partners\",\n        \"Mechanism by which the subcomplex selectively promotes mRNA export is unresolved\",\n        \"Whether NUP160 has functions outside the Nup107-160 complex was not tested\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Genetic studies in Drosophila showed that Nup160 null mutations cause early pupal lethality, female sterility, and hybrid inviability, revealing an essential developmental role and a genetic interaction with Nup96 in speciation.\",\n      \"evidence\": \"Transposon excision null alleles, complementation, and introgression genetics in Drosophila\",\n      \"pmids\": [\"22820383\", \"26022241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical mechanism connecting NUP160-NUP96 interaction to hybrid incompatibility\",\n        \"Cell-type specificity of lethality not resolved\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"NUP160 knockdown in podocytes revealed that it regulates cell proliferation (cyclin D1/CDK4/p27), apoptosis, autophagy, and the expression and localization of slit-diaphragm proteins nephrin, podocin, CD2AP, and α-actinin-4, establishing NUP160 as functionally important in kidney filtration cell biology.\",\n      \"evidence\": \"shRNA knockdown in conditionally immortalized mouse podocytes with flow cytometry, Western blot, and immunofluorescence\",\n      \"pmids\": [\"29704630\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect effects on slit-diaphragm molecules not distinguished\",\n        \"In vivo relevance in mammalian kidney not yet demonstrated at this point\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Drosophila nephrocyte-specific Nup160 silencing caused nuclear membrane disorganization, reduced nuclear volume, and functional defects that were rescued by wild-type human NUP160 but not a pathogenic mutant, directly linking NUP160 to nuclear pore integrity in renal cell types and validating pathogenic allele relevance.\",\n      \"evidence\": \"RNAi in Drosophila nephrocytes with species-swap rescue using human WT vs. mutant NUP160\",\n      \"pmids\": [\"30910934\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the pathogenic mutation's molecular impact on NUP160 structure or interactions not resolved\",\n        \"Whether pore disorganization directly causes the transport defects in nephrocytes was not shown\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"NUP160 was established as a suppressor of autophagy through the NF-κB pathway: its knockdown in kidney tubular cells and diabetic nephropathy mice restored autophagic flux and reduced inflammation and fibrosis.\",\n      \"evidence\": \"siRNA knockdown in high-glucose tubular cells and STZ-induced diabetic mouse model, with Western blot for LC3II/I, p62, and NF-κB\",\n      \"pmids\": [\"34533106\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether NUP160 directly modulates NF-κB signaling or acts via mRNA export changes is unknown\",\n        \"Podocyte vs. tubular cell specificity of the autophagy effect not compared\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Podocyte-specific Nup160 conditional knockout mice developed progressive proteinuria, hypoalbuminemia, and glomerulosclerosis, proving that NUP160 loss in podocytes is sufficient to cause nephrotic syndrome in mammals.\",\n      \"evidence\": \"CRISPR/Cas9 and Cre/loxP conditional KO in mice with urinary albumin, serum albumin, and histopathology\",\n      \"pmids\": [\"38224683\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise molecular cargo whose export is disrupted in NUP160-null podocytes remains unidentified\",\n        \"Whether the phenotype is reversible upon NUP160 re-expression was not tested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Two parallel advances clarified downstream mechanisms: (1) NUP160 loss in podocytes post-transcriptionally reduces CDC42 protein and activity, linking nuclear pore dysfunction to cytoskeletal regulation; (2) IGF2BP2 stabilizes NUP160 mRNA via m6A recognition, and NUP160 suppresses autophagic flux in lung adenocarcinoma.\",\n      \"evidence\": \"Single-cell transcriptomics and proteomics of conditional KO glomeruli (CDC42 finding); RNA pulldown/MS, RIP, m6A-RIP, mRFP-GFP-LC3 flux assay, and xenograft model (IGF2BP2/autophagy finding)\",\n      \"pmids\": [\"40298220\", \"40629330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which NUP160 regulates CDC42 at the post-transcriptional level is not identified\",\n        \"Whether IGF2BP2-mediated NUP160 stabilization occurs in podocytes is untested\",\n        \"Direct NUP160 autophagy target or interactor mediating flux suppression is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of NUP160 integration into the Nup107-160 subcomplex, the identity of specific mRNA cargoes whose export depends on NUP160, and the direct molecular mechanism linking NUP160 to autophagy suppression and CDC42 regulation remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of NUP160 within the assembled pore in vertebrates\",\n        \"Specific mRNA substrates dependent on NUP160 for export have not been catalogued\",\n        \"Whether NUP160's autophagy function is pore-dependent or pore-independent is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [9, 10]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"Nup107-160 complex\"\n    ],\n    \"partners\": [\n      \"NUP133\",\n      \"NUP107\",\n      \"NUP96\",\n      \"SEC13\",\n      \"CDC42\",\n      \"IGF2BP2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"NUP160 is a core scaffold nucleoporin of the Nup107-160 outer-ring subcomplex of the nuclear pore complex, essential for NPC architecture, mRNA export, and kinetochore targeting during mitosis. It forms a stable complex with Nup107, Nup133, Nup96, Sec13, Nup37, Nup43, and Seh1, with 32 copies of this subcomplex assembling into two reticulated rings at the cytoplasmic and nuclear faces of the NPC [PMID:11684705, PMID:11564755, PMID:24315095]. NUP160 is required for poly(A)+ RNA export but dispensable for protein import/export, and its loss in podocytes post-transcriptionally reduces CDC42 protein levels and activity, disrupting cytoskeletal architecture and glomerular filtration [PMID:11684705, PMID:40298220]. Compound-heterozygous mutations in NUP160 cause steroid-resistant nephrotic syndrome, validated by rescue experiments in Drosophila nephrocytes and recapitulated in podocyte-specific knockout mice [PMID:30910934, PMID:38224683].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Identification of NUP160 as a novel vertebrate nucleoporin within a defined NPC subcomplex (with Nup107, Nup133, Nup96, Sec13) resolved the composition of a major outer-ring module and established that NUP160 fragments selectively block mRNA export without affecting protein transport.\",\n      \"evidence\": \"Pulldown from Xenopus egg extracts, co-IP, immunofluorescence, in vivo transport assays in mammalian cells; independently, yeast two-hybrid and reciprocal co-IP in human cells\",\n      \"pmids\": [\"11684705\", \"11564755\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise contact surfaces between NUP160 and other subcomplex members not mapped\", \"Mechanism by which NUP160 selectively facilitates mRNA but not protein export unresolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstration that the entire Nup107-160 complex (now including Nup37, Nup43, Seh1) relocates as a unit to kinetochores during mitosis, with individual subunit depletions phenocopying each other, established functional interdependence and a dual interphase/mitotic role for NUP160.\",\n      \"evidence\": \"GFP-tagging, immunofluorescence, RNAi knockdown, biochemical fractionation in human cells\",\n      \"pmids\": [\"15146057\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct contribution of NUP160 to kinetochore function versus passive co-recruitment not distinguished\", \"Whether mitotic targeting requires NUP160 specifically or any intact subcomplex member unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"High-resolution structural analysis revealed that 32 copies of the Nup107 subcomplex assemble into two reticulated rings at the NPC, defining the stoichiometry and spatial arrangement of NUP160 within the intact human pore scaffold.\",\n      \"evidence\": \"Electron tomography, single-particle EM, crosslinking mass spectrometry of human NPCs\",\n      \"pmids\": [\"24315095\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-resolution contacts of NUP160 within the ring not resolved\", \"Conformational dynamics of NUP160 during cargo translocation unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"BioID proximity labeling using NUP160 fusions as a molecular ruler mapped in vivo spatial relationships within the Nup107-160 complex, confirming its extreme stability and delineating subunit proximity in living cells.\",\n      \"evidence\": \"BioID proximity biotinylation with mass spectrometry in HEK293 cells\",\n      \"pmids\": [\"24927568\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Proximity data do not distinguish direct from indirect contacts\", \"Single study without orthogonal structural validation of the inferred distances\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Discovery of the NUP160-SLC43A3 fusion oncogene in angiosarcomas and its ability to drive endothelial proliferation and tumor formation in vivo revealed that truncation of NUP160 can be oncogenic, raising the question of whether NPC scaffold disruption contributes to tumorigenesis.\",\n      \"evidence\": \"Transcriptome sequencing of angiosarcomas, stable cell line expression, xenograft tumor assay\",\n      \"pmids\": [\"26527604\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Which domains of NUP160 are required for oncogenic activity not determined\", \"Whether the fusion alters NPC-dependent transport or acts through a gain-of-function mechanism unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Genetic analysis in Drosophila showed that Nup160 interacts epistatically with Nup96 to cause hybrid lethality and evolves under recurrent positive selection, linking NPC outer-ring components to speciation barriers.\",\n      \"evidence\": \"Genetic crosses, introgression lines, population genetics in D. simulans/D. melanogaster\",\n      \"pmids\": [\"26022241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of Nup160-Nup96 hybrid incompatibility not identified\", \"Whether the rapid evolution affects NPC transport function or another activity unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identification of compound-heterozygous NUP160 mutations in steroid-resistant nephrotic syndrome patients, with functional validation showing that wild-type but not mutant NUP160 rescues nephrocyte defects in Drosophila, established NUP160 as a causative SRNS gene.\",\n      \"evidence\": \"Whole-exome sequencing, Drosophila nephrocyte RNAi with human NUP160 rescue\",\n      \"pmids\": [\"30910934\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How specific NUP160 mutations impair NPC function at the molecular level unknown\", \"Whether SRNS-associated mutations affect mRNA export, CDC42 regulation, or both not resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Knockdown of NUP160 in mouse podocytes revealed downstream cell-cycle arrest, apoptosis, autophagy induction, and mislocalization of slit-diaphragm proteins, establishing that NUP160 loss has broad effects on podocyte homeostasis beyond NPC function.\",\n      \"evidence\": \"shRNA knockdown in immortalized mouse podocytes, flow cytometry, Western blot, immunofluorescence\",\n      \"pmids\": [\"29704630\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether effects on slit-diaphragm proteins are direct or secondary to NPC dysfunction not distinguished\", \"Single cell-line study without in vivo validation at the time\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Generation of podocyte-specific Nup160 knockout mice confirmed the causal role of NUP160 in glomerular disease by recapitulating progressive proteinuria and glomerulosclerosis in a mammalian model, bridging human genetics and Drosophila studies.\",\n      \"evidence\": \"CRISPR/Cas9 and Cre/loxP conditional knockout mouse, histology, urine ACR, serum albumin\",\n      \"pmids\": [\"38224683\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Temporal requirement for NUP160 in mature versus developing podocytes not defined\", \"Whether the phenotype is fully cell-autonomous or involves paracrine effects not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Multi-omic profiling of Nup160-knockout podocytes revealed that NUP160 loss post-transcriptionally decreases CDC42 protein and activity despite elevated CDC42 mRNA, identifying a shared mechanism with other outer-ring nucleoporin knockouts (NUP85, NUP107, NUP133) and linking NPC scaffold integrity to Rho GTPase-dependent cytoskeletal regulation.\",\n      \"evidence\": \"Conditional KO mouse, dual-fluorescent reporter, single-cell transcriptomics, proteomics, CDC42 activity assay\",\n      \"pmids\": [\"40298220\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of post-transcriptional CDC42 downregulation (translation, stability, or export defect) not determined\", \"Whether restoring CDC42 activity is sufficient to rescue the podocyte phenotype not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular mechanism by which NUP160 (and the Nup107-160 complex) post-transcriptionally controls CDC42 levels in podocytes remains to be determined — whether through selective mRNA export, translational regulation, or protein stability — and whether this mechanism operates in non-podocyte contexts is unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No reconstitution of the CDC42 regulatory mechanism in vitro\", \"Atomic-resolution structure of NUP160 within the intact human NPC not available\", \"Whether NUP160's role in mRNA export and its CDC42-regulatory function are mechanistically linked is unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 3, 4]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\n      \"Nup107-160 complex (Y-complex / outer ring complex)\",\n      \"Nuclear pore complex\"\n    ],\n    \"partners\": [\n      \"NUP107\",\n      \"NUP133\",\n      \"NUP96\",\n      \"SEC13\",\n      \"NUP37\",\n      \"NUP43\",\n      \"SEH1L\",\n      \"CDC42\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}