{"gene":"NSL1","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2014,"finding":"Drosophila Nsl1 mediates kinetochore targeting of Bub3 (spindle assembly checkpoint component); depletion of Nsl1 in epithelial tissues unable to activate apoptosis causes significant aneuploidy and drives tumor-like growth, accompanied by induction of JNK targets Wingless and MMP1.","method":"RNAi-mediated depletion in Drosophila epithelial tissues with apoptosis blockade; aneuploidy quantification and tumor growth readout","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KD with defined cellular phenotype (aneuploidy, tumor growth) and pathway placement (Bub3 kinetochore targeting, JNK signaling), single lab, single model organism","pmids":["24626182"],"is_preprint":false}],"current_model":"NSL1 (Drosophila ortholog Nsl1) functions at the kinetochore as a component required for Bub3 kinetochore targeting and spindle assembly checkpoint signaling; its loss causes chromosomal instability (aneuploidy) and, when apoptosis is blocked, drives tumor-like growth via JNK-dependent induction of mitogenic and matrix-remodeling factors."},"narrative":{"mechanistic_narrative":"NSL1 is a kinetochore component that supports spindle assembly checkpoint signaling by mediating kinetochore targeting of the checkpoint protein Bub3 [PMID:24626182]. In Drosophila epithelial tissues, depletion of Nsl1 causes significant aneuploidy, and when apoptosis is blocked, this chromosomal instability drives tumor-like growth accompanied by JNK-dependent induction of the mitogenic factor Wingless and the matrix-remodeling factor MMP1 [PMID:24626182]. Beyond this single-organism characterization, no further mechanistic detail on NSL1 has been established in the available corpus.","teleology":[{"year":2014,"claim":"Establishing how the spindle assembly checkpoint protein Bub3 is recruited to kinetochores, and what the consequences of failure are, this work placed Nsl1 as the factor required for Bub3 kinetochore targeting and linked its loss to aneuploidy-driven tumorigenesis.","evidence":"RNAi depletion in Drosophila epithelial tissues with apoptosis blockade, scoring aneuploidy, tumor-like growth, and JNK target induction (Wingless, MMP1)","pmids":["24626182"],"confidence":"Medium","gaps":["Direct molecular interaction between Nsl1 and Bub3 not biochemically resolved","Mechanism by which aneuploidy activates JNK signaling not established","Findings limited to a single lab and Drosophila model; human NSL1 function not directly tested"]},{"year":null,"claim":"Whether NSL1 acts within a defined kinetochore subcomplex, how it physically engages Bub3, and whether its checkpoint role is conserved in mammalian cells remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or biochemical characterization of NSL1-containing complexes in the corpus","No mammalian validation of the Bub3-targeting role"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":["kinetochore"],"partners":["BUB3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96IY1","full_name":"Kinetochore-associated protein NSL1 homolog","aliases":[],"length_aa":281,"mass_kda":32.2,"function":"Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis","subcellular_location":"Nucleus; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/Q96IY1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NSL1","classification":"Common Essential","n_dependent_lines":1153,"n_total_lines":1208,"dependency_fraction":0.9544701986754967},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"MIS12","stoichiometry":10.0},{"gene":"CBX1","stoichiometry":0.2},{"gene":"HSPA4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NSL1","total_profiled":1310},"omim":[{"mim_id":"615488","title":"KAT8 REGULATORY NSL COMPLEX, SUBUNIT 2; KANSL2","url":"https://www.omim.org/entry/615488"},{"mim_id":"609174","title":"NSL1, MIS12 KINETOCHORE COMPLEX COMPONENT; NSL1","url":"https://www.omim.org/entry/609174"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear speckles","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NSL1"},"hgnc":{"alias_symbol":["DC8","DKFZP566O1646","MIS14"],"prev_symbol":["C1orf48"]},"alphafold":{"accession":"Q96IY1","domains":[{"cath_id":"-","chopping":"39-91","consensus_level":"high","plddt":92.323,"start":39,"end":91},{"cath_id":"1.20.5","chopping":"105-153","consensus_level":"medium","plddt":93.1661,"start":105,"end":153},{"cath_id":"1.10.287","chopping":"171-220","consensus_level":"medium","plddt":93.18,"start":171,"end":220}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96IY1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96IY1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96IY1-F1-predicted_aligned_error_v6.png","plddt_mean":75.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NSL1","jax_strain_url":"https://www.jax.org/strain/search?query=NSL1"},"sequence":{"accession":"Q96IY1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96IY1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96IY1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96IY1"}},"corpus_meta":[{"pmid":"9862344","id":"PMC_9862344","title":"A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes.","date":"1998","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/9862344","citation_count":138,"is_preprint":false},{"pmid":"20691151","id":"PMC_20691151","title":"A novel class of photo-triggerable liposomes containing DPPC:DC(8,9)PC as vehicles for delivery of doxorubcin to cells.","date":"2010","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/20691151","citation_count":85,"is_preprint":false},{"pmid":"22802339","id":"PMC_22802339","title":"Pivotal role of M-DC8⁺ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products.","date":"2012","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/22802339","citation_count":79,"is_preprint":false},{"pmid":"23825944","id":"PMC_23825944","title":"DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/23825944","citation_count":62,"is_preprint":false},{"pmid":"11385608","id":"PMC_11385608","title":"Phenotype and function of human dendritic cells derived from M-DC8(+) monocytes.","date":"2001","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11385608","citation_count":50,"is_preprint":false},{"pmid":"10879684","id":"PMC_10879684","title":"The M-DC8-positive leukocytes are a subpopulation of the CD14+ CD16+ monocytes.","date":"2000","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/10879684","citation_count":28,"is_preprint":false},{"pmid":"16667766","id":"PMC_16667766","title":"Abscisic Acid Regulation of DC8, A Carrot Embryonic Gene.","date":"1990","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16667766","citation_count":26,"is_preprint":false},{"pmid":"26695549","id":"PMC_26695549","title":"slanDCs/M-DC8+ cells constitute a distinct subset of dendritic cells in human tonsils [corrected].","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/26695549","citation_count":25,"is_preprint":false},{"pmid":"39066482","id":"PMC_39066482","title":"Proxitome profiling reveals a conserved SGT1-NSL1 signaling module that activates NLR-mediated immunity.","date":"2024","source":"Molecular plant","url":"https://pubmed.ncbi.nlm.nih.gov/39066482","citation_count":23,"is_preprint":false},{"pmid":"8639535","id":"PMC_8639535","title":"Raman signature of the four-stranded intercalated cytosine motif in crystal and solution structures of DNA deoxycytidylates d(CCCT) and d(C8).","date":"1996","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8639535","citation_count":21,"is_preprint":false},{"pmid":"1534702","id":"PMC_1534702","title":"Transcriptional regulation of a seed-specific carrot gene, DC8.","date":"1992","source":"Plant molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/1534702","citation_count":20,"is_preprint":false},{"pmid":"24626182","id":"PMC_24626182","title":"Tumor suppressor roles of CENP-E and Nsl1 in Drosophila epithelial tissues.","date":"2014","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/24626182","citation_count":19,"is_preprint":false},{"pmid":"10725804","id":"PMC_10725804","title":"M-DC8+ leukocytes--a novel human dendritic cell population.","date":"1999","source":"Pathobiology : journal of immunopathology, molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10725804","citation_count":17,"is_preprint":false},{"pmid":"15778289","id":"PMC_15778289","title":"Highly efficient antigen targeting to M-DC8+ dendritic cells via FcgammaRIII/CD16-specific antibody conjugates.","date":"2005","source":"International immunology","url":"https://pubmed.ncbi.nlm.nih.gov/15778289","citation_count":16,"is_preprint":false},{"pmid":"26646943","id":"PMC_26646943","title":"Beninese children with cerebral malaria do not develop humoral immunity against the IT4-VAR19-DC8 PfEMP1 variant linked to EPCR and brain endothelial binding.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26646943","citation_count":13,"is_preprint":false},{"pmid":"9549056","id":"PMC_9549056","title":"An apparent case of nonsymmetrical and sustained strand-specific hemimethylation in the Dc8 gene of carrot.","date":"1998","source":"Genome","url":"https://pubmed.ncbi.nlm.nih.gov/9549056","citation_count":12,"is_preprint":false},{"pmid":"35155278","id":"PMC_35155278","title":"Plasmodium falciparum Parasite Lines Expressing DC8 and Group A PfEMP1 Bind to Brain, Intestinal, and Kidney Endothelial Cells.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35155278","citation_count":8,"is_preprint":false},{"pmid":"8704145","id":"PMC_8704145","title":"Expression of DC8 is associated with, but not dependent on embryogenesis.","date":"1996","source":"Plant molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8704145","citation_count":7,"is_preprint":false},{"pmid":"39153451","id":"PMC_39153451","title":"Endogenous retrovirus ERV-DC8 highly integrated in domestic cat populations is a replication-competent provirus.","date":"2024","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/39153451","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.07.22.604565","title":"Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the  <i>Plasmodium falciparum</i>  virulence-associated rosetting phenotype","date":"2024-07-22","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.22.604565","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.06.03.657598","title":"Assembly and phospho-regulatory mechanisms of the budding yeast outer kinetochore KMN complex","date":"2025-06-04","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.03.657598","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.06.652342","title":"Kinetochore mutations and histone phosphorylation pattern changes preceded holo- and macro-monocentromere evolution","date":"2025-05-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.06.652342","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.28.691167","title":"Unconventional components complement the cryptic kinetochore of the ciliate  <i>Tetrahymena thermophila</i>","date":"2025-12-01","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.28.691167","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14410,"output_tokens":940,"usd":0.028665,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6616,"output_tokens":873,"usd":0.027453,"stage2_stop_reason":"end_turn"},"total_usd":0.056118,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify papers about the canonical human/mammalian NSL1 gene (also known as DC8, MIS14, C1orf48, DKFZP566O1646) — which is a kinetochore component involved in chromosome segregation (part of the MIS12 complex).\n\nLet me classify each paper:\n- Papers 1, 3, 5, 6, 8, 13, 14: About M-DC8 antibody/monocyte subpopulation — different gene/antigen, NOT NSL1 kinetochore protein\n- Papers 2, 10: DC8,9 phospholipid / DNA structures — not relevant\n- Papers 4, 15, 17, 20: Plasmodium falciparum DC8 var gene — not relevant\n- Papers 7, 11, 16, 18: Carrot DC8 (Daucus carota LEA protein) — plant gene, symbol collision, skip\n- Paper 9: Plant NSL1 (Nicotiana benthamiana) — plant gene, symbol collision (NSL1 = Necrotic Spotted Lesion 1), skip\n- Paper 12: Drosophila Nsl1 — kinetochore, consistent with mammalian NSL1 function → INCLUDE\n- Paper 19: ERV-DC8 endogenous retrovirus — not relevant\n- Paper 21: Budding yeast KMN complex, cryo-EM — mentions Mis12c/Mtw1c but NSL1 not explicitly mentioned → review\n- Paper 22: NSL1 chimerism in kinetochore evolution — mentions NSL1 → INCLUDE\n- Paper 23: Tetrahymena kinetochore, MIS12 complex — not specifically about NSL1\n\nPaper 21 discusses Knl1c, Mis12c, Ndc80c subunits (Dsn1, Mis12/Mtw1, Nnf1) but doesn't specifically mention NSL1/Nsl1. Skip.\n\nPaper 12: Drosophila Nsl1 — mediates kinetochore targeting of Bub3; depletion causes aneuploidy and tumor-like growth.\nPaper 22: NSL1 chimerism in Chamaelirium luteum kinetochore evolution.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Drosophila Nsl1 mediates kinetochore targeting of Bub3 (spindle assembly checkpoint component); depletion of Nsl1 in epithelial tissues unable to activate apoptosis causes significant aneuploidy and drives tumor-like growth, accompanied by induction of JNK targets Wingless and MMP1.\",\n      \"method\": \"RNAi-mediated depletion in Drosophila epithelial tissues with apoptosis blockade; aneuploidy quantification and tumor growth readout\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KD with defined cellular phenotype (aneuploidy, tumor growth) and pathway placement (Bub3 kinetochore targeting, JNK signaling), single lab, single model organism\",\n      \"pmids\": [\"24626182\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NSL1 (Drosophila ortholog Nsl1) functions at the kinetochore as a component required for Bub3 kinetochore targeting and spindle assembly checkpoint signaling; its loss causes chromosomal instability (aneuploidy) and, when apoptosis is blocked, drives tumor-like growth via JNK-dependent induction of mitogenic and matrix-remodeling factors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NSL1 is a kinetochore component that supports spindle assembly checkpoint signaling by mediating kinetochore targeting of the checkpoint protein Bub3 [#0]. In Drosophila epithelial tissues, depletion of Nsl1 causes significant aneuploidy, and when apoptosis is blocked, this chromosomal instability drives tumor-like growth accompanied by JNK-dependent induction of the mitogenic factor Wingless and the matrix-remodeling factor MMP1 [#0]. Beyond this single-organism characterization, no further mechanistic detail on NSL1 has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing how the spindle assembly checkpoint protein Bub3 is recruited to kinetochores, and what the consequences of failure are, this work placed Nsl1 as the factor required for Bub3 kinetochore targeting and linked its loss to aneuploidy-driven tumorigenesis.\",\n      \"evidence\": \"RNAi depletion in Drosophila epithelial tissues with apoptosis blockade, scoring aneuploidy, tumor-like growth, and JNK target induction (Wingless, MMP1)\",\n      \"pmids\": [\"24626182\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct molecular interaction between Nsl1 and Bub3 not biochemically resolved\",\n        \"Mechanism by which aneuploidy activates JNK signaling not established\",\n        \"Findings limited to a single lab and Drosophila model; human NSL1 function not directly tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether NSL1 acts within a defined kinetochore subcomplex, how it physically engages Bub3, and whether its checkpoint role is conserved in mammalian cells remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or biochemical characterization of NSL1-containing complexes in the corpus\",\n        \"No mammalian validation of the Bub3-targeting role\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"kinetochore\"],\n    \"partners\": [\"Bub3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":2,"faith_total":2,"faith_pct":100.0}}