{"gene":"SNW1","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":1998,"finding":"NCoA-62 (SNW1) directly interacts with the ligand binding domain of the vitamin D receptor (VDR) via protein-protein contact, functioning as a transcriptional coactivator that augments 1,25-dihydroxyvitamin D3-activated transcription but has little effect on basal transcription or Gal4-VP16-activated transcription.","method":"Yeast two-hybrid, GST fusion protein pull-down assays, transient gene expression/reporter assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal yeast two-hybrid and in vitro GST pulldown with functional reporter assays in single lab","pmids":["9632709"],"is_preprint":false},{"year":1998,"finding":"SNW1 (SKIP) interacts with both cellular and viral forms of the Ski oncoprotein through a highly conserved region of Ski required for transforming activity, and SNW1 localizes to the cell nucleus.","method":"Yeast two-hybrid, nuclear localization by subcellular fractionation/immunostaining","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid interaction, single lab, localization reported but limited functional follow-up","pmids":["9569025"],"is_preprint":false},{"year":2001,"finding":"NCoA-62/SKIP (SNW1) forms a ternary complex with the VDR-RXR heterodimer and SRC coactivator proteins; SNW1 contacts a distinct domain from SRC coactivators on VDR (AF-2 independent), and both coactivators synergistically enhance VDR-mediated transcription.","method":"Ternary complex binding assay, LXXLL peptide competition, co-immunoprecipitation, transient transfection reporter assays, protein interference assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal biochemical methods (in vitro binding, competition, functional reporter) establishing distinct interaction interface and cooperative mechanism","pmids":["11514567"],"is_preprint":false},{"year":2003,"finding":"SKIP/NCoA-62 (SNW1) interacts with a conserved, surface-exposed region of VDR helix H10 (an AF-2 independent interface), and this interaction is required for full ligand-dependent transactivation; helix H10 mutants showed reduced interaction with SKIP/NCoA-62, TFIIB, and RXR.","method":"GST pulldown with VDR helix H10 point mutants, transactivation reporter assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — active-site mutagenesis with in vitro binding and functional assay, but single lab","pmids":["12529369"],"is_preprint":false},{"year":2002,"finding":"The Drosophila ortholog Bx42 (SNW1) is essential for Notch signal transduction; RNAi depletion of Bx42 phenocopies Notch mutants, suppresses Notch target genes (cut, Enhancer of split m8), and the wing phenotype is enhanced by overexpression of Suppressor of Hairless.","method":"Inducible RNAi (UAS/GAL4), genetic epistasis with Suppressor of Hairless overexpression, in situ hybridization of Notch target genes","journal":"Mechanisms of development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with defined Notch pathway components and target gene readouts, Drosophila ortholog","pmids":["12204255"],"is_preprint":false},{"year":2002,"finding":"The SNW domain (N-terminal half, aa 1–190) of yeast Prp45 (SNW1 ortholog) is sufficient for essential viability; GFP-tagged Prp45 localizes to nuclear speckles over a diffuse nuclear background; Prp45 can activate transcription of a reporter gene when targeted to DNA.","method":"Complementation assay with deletion constructs in prp45Δ yeast, GFP live imaging, Gal4-fusion transcriptional reporter assay","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mapping by functional complementation, localization by live imaging, transcriptional activity by reporter assay in yeast ortholog","pmids":["12359070"],"is_preprint":false},{"year":2004,"finding":"Human SKIP (SNW1) can functionally complement yeast prp45Δ lethality, demonstrating conserved mRNA splicing function.","method":"Genetic complementation of prp45Δ yeast with human SKIP expression construct","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean functional complementation of lethal deletion, single lab","pmids":["15194481"],"is_preprint":false},{"year":2009,"finding":"Yeast Prp45 (SNW1 ortholog) affects the stoichiometric partitioning of the 2nd-step helicase Prp22 in spliceosomal complexes; prp45(1-169) cells show elevated lariat-exon intermediates at 5' and 3' splice site mutant substrates and pre-mRNA accumulation at branch point mutants, indicating Prp45 contributes to splicing efficiency of non-consensus substrates partly through its interaction with Prp22.","method":"Synthetic lethality screen, Cwc2-pulldown spliceosomal complex purification, in vivo splicing reporter assays with splice site mutants","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic and biochemical (pulldown) evidence for Prp22 interaction and splicing function, single lab with multiple methods","pmids":["19016306"],"is_preprint":false},{"year":2011,"finding":"In Xenopus and zebrafish, SNW1 is required for neural crest specification by regulating a specific domain of BMP activity in the dorsal ectoderm at the neural plate border; SNW1 acts upstream of BMP receptors, and targeted BMP overexpression at the neural plate border rescues neural crest formation in SNW1 morphants.","method":"Antisense morpholino knockdown in Xenopus and zebrafish, immunostaining for phospho-Smad1, BMP reporter transgenic zebrafish, tissue explants, epistasis rescue experiments","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — two vertebrate model organisms, multiple orthogonal assays (pSmad1 immunostaining, transgenic reporter, rescue by BMP overexpression), pathway position established by epistasis","pmids":["21358802"],"is_preprint":false},{"year":2014,"finding":"SNW1 is an essential spliceosome subunit required for sister chromatid cohesion; SNW1 depletion causes mis-splicing of specific introns in sororin and APC2 pre-mRNAs, reducing sororin levels (destabilizing cohesin on DNA) and APC/C activity; simultaneous intron-less cDNA expression of sororin and APC2 rescues cohesion defects in SNW1-depleted cells.","method":"siRNA knockdown, transcriptome-wide splicing analysis (RNA-seq), live-cell imaging (sister chromatid cohesion assay), intron-less cDNA rescue, western blot","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — transcriptome-wide analysis combined with mechanistic rescue experiments (intron-less cDNA), defines both molecular substrate and cellular phenotype","pmids":["25257309"],"is_preprint":false},{"year":2014,"finding":"SNW1 directly associates with spliceosomal proteins EFTUD2 (Snu114) and SNRNP200 (Brr2); the SKIP region of SNW1 interacts with the N-terminus of EFTUD2 and two independent regions in the C-terminus of SNRNP200; depletion of SNW1 or EFTUD2 induces apoptosis in breast cancer cells.","method":"Proteomics, co-immunoprecipitation, domain mapping with deletion constructs, siRNA knockdown with apoptosis assay","journal":"Cancer medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal biochemical interaction mapping with domain deletion constructs plus functional knockdown phenotype, single lab","pmids":["25450007"],"is_preprint":false},{"year":2015,"finding":"Yeast Prp45 (SNW1 ortholog) crosslinks to nucleotides surrounding the pre-mRNA branch-site upon step 1 catalysis in the spliceosome; these contacts are enhanced in B* and C complexes compared to Bact, indicating dynamic interaction of Prp45 with the pre-mRNA during catalytic activation.","method":"UV-induced crosslinking of purified yeast spliceosomal complexes (Bact, B*, C) on site-specifically labeled pre-mRNA, mass spectrometry","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous in vitro crosslinking with purified complexes but single study for the Prp45-specific contacts","pmids":["26393790"],"is_preprint":false},{"year":2017,"finding":"Yeast Prp45 (SNW1 ortholog) is required for early cotranscriptional spliceosome assembly; truncated Prp45(1-169) impairs cotranscriptional recruitment of U2 snRNP and, more strongly, U5 snRNP and NTC, while U1 snRNP recruitment is unaffected, indicating Prp45 facilitates conformational rearrangements coupling U1 snRNP recognition to downstream assembly (complex A formation).","method":"RNA-seq, RT-qPCR, splicing reporters, chromatin immunoprecipitation (ChIP) along gene bodies for spliceosome components","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-based cotranscriptional assembly assay with defined genetic allele, multiple target genes examined, single lab","pmids":["28701519"],"is_preprint":false},{"year":2019,"finding":"SNW1 acts as a transcriptional regulator of the NF-κB pathway by complexing with the NF-κB heterodimer in the nucleus; upon NF-κB activation, SNW1 detaches from its spliceosomal complex (with SNRNP200 and SNRNP220) and binds to the NF-κB transcriptional elongation partner p-TEFb, and is required for transcriptional elongation of NF-κB target genes IL-8 and TNF.","method":"Genome-wide RNAi screen, co-immunoprecipitation, siRNA knockdown with reporter and endogenous gene expression assays","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide screen hit validated by co-IP and functional knockdown with defined target genes, single lab","pmids":["30397075"],"is_preprint":false},{"year":2019,"finding":"SNW1 interacts with RBPJ to regulate Notch target gene expression in neuroblastoma; silencing RBPJ blocks SNW1-mediated Notch gene expression.","method":"Co-immunoprecipitation, siRNA knockdown of RBPJ, luciferase reporter assay for Notch targets","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP with limited functional follow-up, single lab","pmids":["30642633"],"is_preprint":false},{"year":2020,"finding":"SNW1 interacts with IKKγ (regulatory subunit of IκB kinase complex) to promote influenza A virus-induced activation of NF-κB and phosphorylation of TBK1, thereby increasing pro-inflammatory cytokines and IFN-β expression.","method":"Co-immunoprecipitation, SNW1 depletion/overexpression with reporter and ELISA assays, western blot for pathway activation","journal":"Microbes and infection","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP for IKKγ interaction, functional data from OE/KD, single lab","pmids":["32805409"],"is_preprint":false},{"year":2022,"finding":"O-GlcNAcylation of SNW1 negatively regulates its ability to activate NF-κB p65 transcriptional activity; dexmedetomidine upregulates OGT-mediated O-GlcNAcylation of SNW1, reducing SNW1/NF-κB complex formation and inflammatory gene expression in neurons undergoing ischemia-reperfusion.","method":"Immunoprecipitation to detect O-GlcNAc on SNW1, luciferase reporter assay for NF-κB activity, OGT inhibitor experiments, ELISA for inflammatory factors, in vivo MCAO model","journal":"Journal of neuropathology and experimental neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct detection of PTM on SNW1 by IP, functional reporter assay, multiple in vitro and in vivo readouts, single lab","pmids":["35818332"],"is_preprint":false},{"year":2024,"finding":"SNW1 promotes SRPK1 splicing by interacting with core spliceosome components NUDT21 and CPSF6, producing opposite expression changes in two distinct SRPK1 transcripts; SNW1's pro-metastatic effect in bladder cancer is dependent on SRPK1 protein expression.","method":"Co-immunoprecipitation, siRNA knockdown, RT-PCR splicing assay, invasion/migration assays","journal":"iScience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP and rescue experiments, single lab, limited mechanistic depth","pmids":["41704767"],"is_preprint":false},{"year":2024,"finding":"DSA (a monomer of Antrodia cinnamomea triterpenoids) binds SNW1 as a target protein; SNW1 promotes ALDH2 transcription and translation through synergistic interaction with the transcription factor RXR.","method":"Target fishing/cellular thermal shift assay for DSA-SNW1 binding, co-immunoprecipitation of SNW1-RXR, ALDH2 expression and activity assays","journal":"Redox biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — target engagement by thermal shift and co-IP, single lab with limited mechanistic follow-up","pmids":["39591904"],"is_preprint":false},{"year":2025,"finding":"The C-terminal region of yeast Prp45 (SNW1 ortholog) physically and functionally interacts with Lge1 (scaffold protein essential for the H2B ubiquitin ligase complex Bre1), stabilizing Lge1 and thereby promoting histone H2B ubiquitination; loss of the Prp45 C-terminus causes severe loss of H2B ubiquitination; the C-terminal IDR/helical domain from humans or plants can restore Lge1 stability and H2B ubiquitination in yeast.","method":"Genetic analysis (truncation alleles), proteomics (pulldown-MS), biochemical co-IP, western blot for H2B ubiquitination, cross-species complementation","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (genetics, proteomics, biochemistry, cross-species complementation) in a single preprint study","pmids":["40667372"],"is_preprint":true},{"year":2025,"finding":"Mutations in SNW1 impair its interactions with core spliceosomal proteins, causing defective RNA splicing (especially exon skipping) and reduced neural stem cell proliferation with increased apoptosis; disrupted alternative splicing of CENPE, MEF2C, and NRXN2 genes is observed in SNW1-depleted cerebral organoids and Drosophila.","method":"Patient mutation analysis, co-immunoprecipitation (mutant vs wild-type interactions), RNA-seq splicing analysis, Drosophila RNAi knockdown, human cerebral organoid model with siRNA depletion","journal":"The Journal of clinical investigation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple model systems and orthogonal methods establishing splicing mechanism, though single study","pmids":["40608414"],"is_preprint":false},{"year":2024,"finding":"SNW1 is found in a chromatin-associated complex with SF3B1, P-TEFb, and the elongation/splicing factor HTATSF1; SF3B1 inhibition causes nuclear export of SNW1 (but not HTATSF1), contributing to decreased P-TEFb recruitment to chromatin.","method":"Co-immunoprecipitation, nuclear/cytoplasmic fractionation, chromatin immunoprecipitation after SF3B1 inhibitor treatment","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single preprint, Co-IP interaction and fractionation, limited functional follow-up specific to SNW1","pmids":[],"is_preprint":true}],"current_model":"SNW1 (also known as SKIP, NCoA-62, Prp45) is a dual-function nuclear protein that operates as both a spliceosome component and a transcriptional coactivator: within the spliceosome it makes dynamic contacts with the pre-mRNA branch-site region during catalytic activation, facilitates cotranscriptional recruitment of U2, U5, and NTC complexes, and enables splicing of specific introns (including those in sororin and APC2) required for sister chromatid cohesion and mitosis; in transcription it interacts directly with the VDR-RXR heterodimer at helix H10 (AF-2-independent) and with SRC coactivators to synergistically drive nuclear-receptor-mediated gene expression, complexes with NF-κB and p-TEFb to promote transcriptional elongation of inflammatory target genes, and its C-terminus stabilizes the Lge1 scaffold of the Bre1 H2B ubiquitin ligase, linking splicing to active transcription elongation through histone modification."},"narrative":{"mechanistic_narrative":"SNW1 (SKIP/NCoA-62; yeast Prp45) is a dual-function nuclear protein that couples pre-mRNA splicing to transcriptional regulation [PMID:25257309, PMID:11514567]. As an essential spliceosome subunit, it associates directly with the core splicing machinery EFTUD2 (Snu114) and SNRNP200 (Brr2) through defined interaction surfaces [PMID:25450007], makes dynamic contacts with nucleotides flanking the pre-mRNA branch site during catalytic activation [PMID:26393790], and is required for early cotranscriptional recruitment of U2 and U5 snRNPs and the NTC, downstream of U1 recognition [PMID:28701519]. Through this activity SNW1 enables splicing of specific introns in sororin and APC2 needed for sister chromatid cohesion and APC/C activity, with intron-less cDNA expression of these substrates rescuing cohesion defects in SNW1-depleted cells [PMID:25257309]. In its transcriptional role, SNW1 acts as a coactivator that contacts the vitamin D receptor at an AF-2-independent surface of helix H10 and cooperates with SRC coactivators in a ternary complex with the VDR-RXR heterodimer to synergistically drive ligand-dependent transcription [PMID:11514567, PMID:12529369]. SNW1 also detaches from the spliceosome to bind the NF-κB heterodimer and the elongation factor p-TEFb, driving transcriptional elongation of inflammatory target genes such as IL-8 and TNF [PMID:30397075], an activity negatively regulated by OGT-mediated O-GlcNAcylation of SNW1 [PMID:35818332]. Developmentally, SNW1 is required for neural crest specification by setting a BMP-activity domain at the neural plate border upstream of BMP receptors [PMID:21358802], and patient mutations that impair SNW1 contacts with core spliceosomal proteins cause exon-skipping defects and reduced neural stem cell proliferation in cerebral organoids and Drosophila [PMID:40608414]. A C-terminal region of the protein additionally stabilizes the Lge1 scaffold of the Bre1 H2B ubiquitin ligase, linking SNW1 to histone H2B ubiquitination [PMID:40667372].","teleology":[{"year":1998,"claim":"Established SNW1's first molecular role by showing it binds the vitamin D receptor and acts as a ligand-specific transcriptional coactivator, defining it as more than a generic factor.","evidence":"Yeast two-hybrid, GST pull-down, and reporter assays with VDR; parallel two-hybrid with the Ski oncoprotein and nuclear localization","pmids":["9632709","9569025"],"confidence":"Medium","gaps":["Did not resolve the VDR interaction interface","No structural model of the coactivator contact","Functional role in splicing not yet recognized"]},{"year":2001,"claim":"Defined how SNW1 cooperates with other coactivators, showing it engages a VDR surface distinct from SRC proteins to synergistically enhance nuclear-receptor transcription.","evidence":"Ternary complex binding, LXXLL peptide competition, co-IP, and reporter assays; later mapped to VDR helix H10 by point-mutant pull-downs","pmids":["11514567","12529369"],"confidence":"High","gaps":["AF-2-independent interface mapped functionally but not structurally","Generalization beyond VDR to other nuclear receptors not established"]},{"year":2002,"claim":"Connected SNW1 to conserved developmental signaling and splicing through model organisms, establishing both Notch-pathway requirement and an essential N-terminal SNW domain.","evidence":"Drosophila Bx42 RNAi with Notch genetic epistasis and target-gene readouts; yeast Prp45 domain complementation, GFP speckle localization, and Gal4-fusion reporter","pmids":["12204255","12359070"],"confidence":"Medium","gaps":["Whether Notch effect is direct or via splicing not resolved","Molecular function of the SNW domain undefined"]},{"year":2004,"claim":"Demonstrated functional conservation of the splicing role by showing human SKIP rescues lethality of the yeast Prp45 deletion.","evidence":"Genetic complementation of prp45Δ yeast with human SKIP","pmids":["15194481"],"confidence":"Medium","gaps":["Complementation shows conserved function but not mechanistic detail","Substrate specificity in human cells not addressed"]},{"year":2009,"claim":"Began to localize SNW1's action within the spliceosome by linking yeast Prp45 to the second-step helicase Prp22 and to splicing efficiency of non-consensus substrates.","evidence":"Synthetic lethality screen, Cwc2-pulldown complex purification, and in vivo splicing reporters with splice-site mutants","pmids":["19016306"],"confidence":"Medium","gaps":["Direct vs indirect Prp22 interaction not fully resolved","Human relevance of the Prp22 link untested"]},{"year":2011,"claim":"Placed SNW1 in vertebrate development by showing it patterns a BMP-activity domain upstream of BMP receptors to specify neural crest.","evidence":"Morpholino knockdown in Xenopus and zebrafish, pSmad1 immunostaining, BMP reporter transgenics, and rescue by targeted BMP overexpression","pmids":["21358802"],"confidence":"High","gaps":["Whether BMP regulation is via splicing of pathway components unknown","Direct molecular target within the BMP axis not identified"]},{"year":2014,"claim":"Resolved how SNW1 connects splicing to mitosis, identifying sororin and APC2 introns as critical substrates whose mis-splicing explains cohesion defects, and mapping direct contacts to EFTUD2 and SNRNP200.","evidence":"siRNA knockdown with RNA-seq splicing analysis, live-cell cohesion imaging, intron-less cDNA rescue; proteomics and reciprocal domain-mapped co-IP","pmids":["25257309","25450007"],"confidence":"High","gaps":["Why specific introns depend on SNW1 not mechanistically explained","Structural basis of EFTUD2/SNRNP200 contacts unresolved"]},{"year":2017,"claim":"Defined the step at which SNW1 acts in spliceosome assembly, showing yeast Prp45 contacts the branch site during catalytic activation and is needed for cotranscriptional U2/U5/NTC recruitment after U1 recognition.","evidence":"UV crosslinking of purified Bact/B*/C complexes with mass spectrometry; ChIP along gene bodies for spliceosome components with the prp45(1-169) allele","pmids":["26393790","28701519"],"confidence":"Medium","gaps":["Human conservation of these assembly-stage roles not directly tested","How Prp45 drives the conformational coupling mechanistically unclear"]},{"year":2019,"claim":"Revealed a regulated switch from spliceosome to transcription, with SNW1 detaching from the spliceosome to bind NF-κB and p-TEFb and drive elongation of inflammatory genes, and engaging RBPJ for Notch targets.","evidence":"Genome-wide RNAi screen, co-IP, and knockdown with target-gene expression for NF-κB; co-IP and reporter assays for RBPJ in neuroblastoma","pmids":["30397075","30642633"],"confidence":"Medium","gaps":["Trigger and kinetics of the spliceosome-to-NF-κB switch undefined","RBPJ interaction rests on a single Co-IP without reciprocal validation"]},{"year":2020,"claim":"Extended SNW1's NF-κB role to innate antiviral signaling, showing it engages IKKγ to promote influenza-induced NF-κB and TBK1 activation.","evidence":"Co-IP, depletion/overexpression with reporter and ELISA, and western blot for pathway activation","pmids":["32805409"],"confidence":"Low","gaps":["IKKγ interaction from a single Co-IP without reciprocal confirmation","Direct vs indirect engagement unresolved"]},{"year":2022,"claim":"Identified a post-translational control point, showing O-GlcNAcylation of SNW1 suppresses its NF-κB-activating function.","evidence":"IP-based detection of O-GlcNAc on SNW1, NF-κB reporter, OGT-inhibitor experiments, ELISA, and an in vivo MCAO model","pmids":["35818332"],"confidence":"Medium","gaps":["Modified residue(s) on SNW1 not mapped","Whether O-GlcNAcylation also affects splicing function untested"]},{"year":2024,"claim":"Broadened the splicing repertoire and disease relevance, linking SNW1 to SRPK1 transcript choice via NUDT21/CPSF6 and to a chromatin complex with SF3B1, P-TEFb, and HTATSF1.","evidence":"Co-IP, knockdown, RT-PCR splicing and invasion assays for SRPK1; co-IP, fractionation and ChIP after SF3B1 inhibition (preprint); DSA target-engagement and SNW1-RXR co-IP for ALDH2","pmids":["41704767","39591904"],"confidence":"Low","gaps":["SRPK1 and ALDH2 mechanisms rest on single-lab Co-IP/rescue","SF3B1/P-TEFb complex evidence is a preprint with limited SNW1-specific follow-up"]},{"year":2025,"claim":"Established a human disease link and a new C-terminal function, showing pathogenic SNW1 mutations disrupt spliceosomal contacts and exon inclusion to impair neurodevelopment, while the C-terminus stabilizes the Lge1 scaffold to promote H2B ubiquitination.","evidence":"Patient mutation analysis, mutant-vs-WT co-IP, RNA-seq, Drosophila RNAi and cerebral organoid models; truncation genetics, pulldown-MS, H2B-ubiquitination western blot and cross-species complementation (preprint)","pmids":["40608414","40667372"],"confidence":"Medium","gaps":["Genotype-phenotype spectrum of SNW1 mutations not fully delineated","Lge1/Bre1 link demonstrated in yeast with cross-species rescue but not in human cells","How splicing and H2B-ubiquitination roles are coordinated unknown"]},{"year":null,"claim":"How SNW1 dynamically partitions between its spliceosomal and transcriptional/chromatin roles, and what governs substrate intron selectivity, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of SNW1 within the human spliceosome","Signals controlling the spliceosome-to-transcription switch unknown","Rules determining which introns require SNW1 undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,2,13]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[9,11,12]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,10,19]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[11]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,5]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[5,13]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[21]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[9,11,12]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[2,13]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[9]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[13]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[8,20]}],"complexes":["spliceosome","VDR-RXR-SRC coactivator complex","NF-κB/p-TEFb elongation complex"],"partners":["VDR","RXR","EFTUD2","SNRNP200","RBPJ","IKBKG","SF3B1","LGE1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13573","full_name":"SNW domain-containing protein 1","aliases":["Nuclear protein SkiP","Nuclear receptor coactivator NCoA-62","Ski-interacting protein"],"length_aa":536,"mass_kda":61.5,"function":"Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q13573/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SNW1","classification":"Common Essential","n_dependent_lines":1208,"n_total_lines":1208,"dependency_fraction":1.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"PRPF4B","stoichiometry":4.0},{"gene":"SF3A2","stoichiometry":4.0},{"gene":"CD2BP2","stoichiometry":0.2},{"gene":"CPSF6","stoichiometry":0.2},{"gene":"RBM14","stoichiometry":0.2},{"gene":"RBM33","stoichiometry":0.2},{"gene":"RBM39","stoichiometry":0.2},{"gene":"RBM42","stoichiometry":0.2},{"gene":"RBM6","stoichiometry":0.2},{"gene":"SF3A1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SNW1","total_profiled":1310},"omim":[{"mim_id":"618083","title":"WW-BINDING PROTEIN 11; WBP11","url":"https://www.omim.org/entry/618083"},{"mim_id":"603055","title":"SKI-INTERACTING PROTEIN; SKIIP","url":"https://www.omim.org/entry/603055"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNW1"},"hgnc":{"alias_symbol":["NCoA-62","SKIP","Prp45","PRPF45","Bx42","SKIP1","FUN20"],"prev_symbol":["SKIIP"]},"alphafold":{"accession":"Q13573","domains":[{"cath_id":"-","chopping":"35-119","consensus_level":"medium","plddt":89.4834,"start":35,"end":119},{"cath_id":"1.20.5","chopping":"284-332","consensus_level":"medium","plddt":92.1141,"start":284,"end":332}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13573","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13573-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13573-F1-predicted_aligned_error_v6.png","plddt_mean":78.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNW1","jax_strain_url":"https://www.jax.org/strain/search?query=SNW1"},"sequence":{"accession":"Q13573","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13573.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13573/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13573"}},"corpus_meta":[{"pmid":"9632709","id":"PMC_9632709","title":"Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9632709","citation_count":113,"is_preprint":false},{"pmid":"9569025","id":"PMC_9569025","title":"The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42.","date":"1998","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/9569025","citation_count":94,"is_preprint":false},{"pmid":"11514567","id":"PMC_11514567","title":"Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11514567","citation_count":60,"is_preprint":false},{"pmid":"25257309","id":"PMC_25257309","title":"SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs.","date":"2014","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/25257309","citation_count":49,"is_preprint":false},{"pmid":"25450007","id":"PMC_25450007","title":"Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells.","date":"2014","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25450007","citation_count":37,"is_preprint":false},{"pmid":"21358802","id":"PMC_21358802","title":"SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos.","date":"2011","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/21358802","citation_count":37,"is_preprint":false},{"pmid":"12529369","id":"PMC_12529369","title":"Interactions of SKIP/NCoA-62, TFIIB, and retinoid X receptor with vitamin D receptor helix H10 residues.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12529369","citation_count":35,"is_preprint":false},{"pmid":"26393790","id":"PMC_26393790","title":"Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes.","date":"2015","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26393790","citation_count":31,"is_preprint":false},{"pmid":"19016306","id":"PMC_19016306","title":"Prp45 affects Prp22 partition in spliceosomal complexes and splicing efficiency of non-consensus substrates.","date":"2009","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19016306","citation_count":31,"is_preprint":false},{"pmid":"30397075","id":"PMC_30397075","title":"SNW1, a Novel Transcriptional Regulator of the NF-κB Pathway.","date":"2019","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/30397075","citation_count":27,"is_preprint":false},{"pmid":"1424996","id":"PMC_1424996","title":"The Drosophila nuclear protein Bx42, which is found in many puffs on polytene chromosomes, is highly charged.","date":"1992","source":"Chromosoma","url":"https://pubmed.ncbi.nlm.nih.gov/1424996","citation_count":24,"is_preprint":false},{"pmid":"12204255","id":"PMC_12204255","title":"Inducible RNA interference uncovers the Drosophila protein Bx42 as an essential nuclear cofactor involved in Notch signal transduction.","date":"2002","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/12204255","citation_count":23,"is_preprint":false},{"pmid":"8973337","id":"PMC_8973337","title":"The homolog of chromatin binding protein Bx42 identified in Dictyostelium.","date":"1996","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8973337","citation_count":21,"is_preprint":false},{"pmid":"15194481","id":"PMC_15194481","title":"The human Ski-interacting protein functionally substitutes for the yeast PRP45 gene.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15194481","citation_count":18,"is_preprint":false},{"pmid":"30642633","id":"PMC_30642633","title":"SNW1 regulates Notch signaling in neuroblastoma through interacting with RBPJ.","date":"2019","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/30642633","citation_count":16,"is_preprint":false},{"pmid":"12359070","id":"PMC_12359070","title":"Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability.","date":"2002","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12359070","citation_count":16,"is_preprint":false},{"pmid":"28701519","id":"PMC_28701519","title":"Nineteen complex-related factor Prp45 is required for the early stages of cotranscriptional spliceosome assembly.","date":"2017","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/28701519","citation_count":11,"is_preprint":false},{"pmid":"32805409","id":"PMC_32805409","title":"SNW1 interacts with IKKγ to positively regulate antiviral innate immune responses against influenza A virus infection.","date":"2020","source":"Microbes and infection","url":"https://pubmed.ncbi.nlm.nih.gov/32805409","citation_count":8,"is_preprint":false},{"pmid":"39591904","id":"PMC_39591904","title":"Antrodia cinnamomea triterpenoids attenuate cardiac hypertrophy via the SNW1/RXR/ALDH2 axis.","date":"2024","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/39591904","citation_count":5,"is_preprint":false},{"pmid":"21461980","id":"PMC_21461980","title":"Stress-induced expression of p53 target genes is insensitive to SNW1/SKIP downregulation.","date":"2011","source":"Cellular & molecular biology letters","url":"https://pubmed.ncbi.nlm.nih.gov/21461980","citation_count":5,"is_preprint":false},{"pmid":"35818332","id":"PMC_35818332","title":"Dexmedetomidine Inhibits NF-κB-Transcriptional Activity in Neurons Undergoing Ischemia-Reperfusion by Regulating O-GlcNAcylation of SNW1.","date":"2022","source":"Journal of neuropathology and experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/35818332","citation_count":4,"is_preprint":false},{"pmid":"40608414","id":"PMC_40608414","title":"Mutations in the spliceosomal gene SNW1 cause neurodevelopment disorders with microcephaly.","date":"2025","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/40608414","citation_count":2,"is_preprint":false},{"pmid":"39905161","id":"PMC_39905161","title":"Integration of transcriptomics and metabolomics data revealed role of insulin resistant SNW1 gene in the pathophysiology of gestational diabetes.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39905161","citation_count":2,"is_preprint":false},{"pmid":"38711165","id":"PMC_38711165","title":"Truncating the spliceosomal 'rope protein' Prp45 results in Htz1 dependent phenotypes.","date":"2024","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/38711165","citation_count":1,"is_preprint":false},{"pmid":"39730520","id":"PMC_39730520","title":"Phosphorylation of SNW1 protein associated with equine melanocytic neoplasm identified in serum and feces.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39730520","citation_count":1,"is_preprint":false},{"pmid":"39093930","id":"PMC_39093930","title":"Genomic characterization of SNW-1, a novel prophage of the deep-sea vent chemolithoautotroph Sulfurimonas indica NW79.","date":"2024","source":"Genetics and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/39093930","citation_count":1,"is_preprint":false},{"pmid":"32692995","id":"PMC_32692995","title":"A novel SNW/SKIP domain-containing protein, Bx42, is involved in the antibacterial responses of Macrobrachium nipponense.","date":"2020","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/32692995","citation_count":0,"is_preprint":false},{"pmid":"40667372","id":"PMC_40667372","title":"The RNA splicing factor Prp45 directs histone H2B ubiquitination through its C-terminal domain.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40667372","citation_count":0,"is_preprint":false},{"pmid":"41704767","id":"PMC_41704767","title":"SNW1 promotes lymphatic metastasis in bladder cancer by modulating SRPK1 splicing.","date":"2026","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/41704767","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.18.660225","title":"The RNA splicing factor Prp45 plays an evolutionarily conserved role in histone H2B ubiquitination","date":"2025-06-18","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.18.660225","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.06.26.600844","title":"Inhibition of SF3B1 affects recruitment of P-TEFb to chromatin through multiple mechanisms","date":"2024-06-27","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.26.600844","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15819,"output_tokens":5375,"usd":0.064041,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13739,"output_tokens":4802,"usd":0.094372,"stage2_stop_reason":"end_turn"},"total_usd":0.158413,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"NCoA-62 (SNW1) directly interacts with the ligand binding domain of the vitamin D receptor (VDR) via protein-protein contact, functioning as a transcriptional coactivator that augments 1,25-dihydroxyvitamin D3-activated transcription but has little effect on basal transcription or Gal4-VP16-activated transcription.\",\n      \"method\": \"Yeast two-hybrid, GST fusion protein pull-down assays, transient gene expression/reporter assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal yeast two-hybrid and in vitro GST pulldown with functional reporter assays in single lab\",\n      \"pmids\": [\"9632709\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"SNW1 (SKIP) interacts with both cellular and viral forms of the Ski oncoprotein through a highly conserved region of Ski required for transforming activity, and SNW1 localizes to the cell nucleus.\",\n      \"method\": \"Yeast two-hybrid, nuclear localization by subcellular fractionation/immunostaining\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid interaction, single lab, localization reported but limited functional follow-up\",\n      \"pmids\": [\"9569025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"NCoA-62/SKIP (SNW1) forms a ternary complex with the VDR-RXR heterodimer and SRC coactivator proteins; SNW1 contacts a distinct domain from SRC coactivators on VDR (AF-2 independent), and both coactivators synergistically enhance VDR-mediated transcription.\",\n      \"method\": \"Ternary complex binding assay, LXXLL peptide competition, co-immunoprecipitation, transient transfection reporter assays, protein interference assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal biochemical methods (in vitro binding, competition, functional reporter) establishing distinct interaction interface and cooperative mechanism\",\n      \"pmids\": [\"11514567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"SKIP/NCoA-62 (SNW1) interacts with a conserved, surface-exposed region of VDR helix H10 (an AF-2 independent interface), and this interaction is required for full ligand-dependent transactivation; helix H10 mutants showed reduced interaction with SKIP/NCoA-62, TFIIB, and RXR.\",\n      \"method\": \"GST pulldown with VDR helix H10 point mutants, transactivation reporter assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — active-site mutagenesis with in vitro binding and functional assay, but single lab\",\n      \"pmids\": [\"12529369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The Drosophila ortholog Bx42 (SNW1) is essential for Notch signal transduction; RNAi depletion of Bx42 phenocopies Notch mutants, suppresses Notch target genes (cut, Enhancer of split m8), and the wing phenotype is enhanced by overexpression of Suppressor of Hairless.\",\n      \"method\": \"Inducible RNAi (UAS/GAL4), genetic epistasis with Suppressor of Hairless overexpression, in situ hybridization of Notch target genes\",\n      \"journal\": \"Mechanisms of development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with defined Notch pathway components and target gene readouts, Drosophila ortholog\",\n      \"pmids\": [\"12204255\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The SNW domain (N-terminal half, aa 1–190) of yeast Prp45 (SNW1 ortholog) is sufficient for essential viability; GFP-tagged Prp45 localizes to nuclear speckles over a diffuse nuclear background; Prp45 can activate transcription of a reporter gene when targeted to DNA.\",\n      \"method\": \"Complementation assay with deletion constructs in prp45Δ yeast, GFP live imaging, Gal4-fusion transcriptional reporter assay\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mapping by functional complementation, localization by live imaging, transcriptional activity by reporter assay in yeast ortholog\",\n      \"pmids\": [\"12359070\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Human SKIP (SNW1) can functionally complement yeast prp45Δ lethality, demonstrating conserved mRNA splicing function.\",\n      \"method\": \"Genetic complementation of prp45Δ yeast with human SKIP expression construct\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean functional complementation of lethal deletion, single lab\",\n      \"pmids\": [\"15194481\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Yeast Prp45 (SNW1 ortholog) affects the stoichiometric partitioning of the 2nd-step helicase Prp22 in spliceosomal complexes; prp45(1-169) cells show elevated lariat-exon intermediates at 5' and 3' splice site mutant substrates and pre-mRNA accumulation at branch point mutants, indicating Prp45 contributes to splicing efficiency of non-consensus substrates partly through its interaction with Prp22.\",\n      \"method\": \"Synthetic lethality screen, Cwc2-pulldown spliceosomal complex purification, in vivo splicing reporter assays with splice site mutants\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic and biochemical (pulldown) evidence for Prp22 interaction and splicing function, single lab with multiple methods\",\n      \"pmids\": [\"19016306\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In Xenopus and zebrafish, SNW1 is required for neural crest specification by regulating a specific domain of BMP activity in the dorsal ectoderm at the neural plate border; SNW1 acts upstream of BMP receptors, and targeted BMP overexpression at the neural plate border rescues neural crest formation in SNW1 morphants.\",\n      \"method\": \"Antisense morpholino knockdown in Xenopus and zebrafish, immunostaining for phospho-Smad1, BMP reporter transgenic zebrafish, tissue explants, epistasis rescue experiments\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two vertebrate model organisms, multiple orthogonal assays (pSmad1 immunostaining, transgenic reporter, rescue by BMP overexpression), pathway position established by epistasis\",\n      \"pmids\": [\"21358802\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SNW1 is an essential spliceosome subunit required for sister chromatid cohesion; SNW1 depletion causes mis-splicing of specific introns in sororin and APC2 pre-mRNAs, reducing sororin levels (destabilizing cohesin on DNA) and APC/C activity; simultaneous intron-less cDNA expression of sororin and APC2 rescues cohesion defects in SNW1-depleted cells.\",\n      \"method\": \"siRNA knockdown, transcriptome-wide splicing analysis (RNA-seq), live-cell imaging (sister chromatid cohesion assay), intron-less cDNA rescue, western blot\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — transcriptome-wide analysis combined with mechanistic rescue experiments (intron-less cDNA), defines both molecular substrate and cellular phenotype\",\n      \"pmids\": [\"25257309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SNW1 directly associates with spliceosomal proteins EFTUD2 (Snu114) and SNRNP200 (Brr2); the SKIP region of SNW1 interacts with the N-terminus of EFTUD2 and two independent regions in the C-terminus of SNRNP200; depletion of SNW1 or EFTUD2 induces apoptosis in breast cancer cells.\",\n      \"method\": \"Proteomics, co-immunoprecipitation, domain mapping with deletion constructs, siRNA knockdown with apoptosis assay\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal biochemical interaction mapping with domain deletion constructs plus functional knockdown phenotype, single lab\",\n      \"pmids\": [\"25450007\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Yeast Prp45 (SNW1 ortholog) crosslinks to nucleotides surrounding the pre-mRNA branch-site upon step 1 catalysis in the spliceosome; these contacts are enhanced in B* and C complexes compared to Bact, indicating dynamic interaction of Prp45 with the pre-mRNA during catalytic activation.\",\n      \"method\": \"UV-induced crosslinking of purified yeast spliceosomal complexes (Bact, B*, C) on site-specifically labeled pre-mRNA, mass spectrometry\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous in vitro crosslinking with purified complexes but single study for the Prp45-specific contacts\",\n      \"pmids\": [\"26393790\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Yeast Prp45 (SNW1 ortholog) is required for early cotranscriptional spliceosome assembly; truncated Prp45(1-169) impairs cotranscriptional recruitment of U2 snRNP and, more strongly, U5 snRNP and NTC, while U1 snRNP recruitment is unaffected, indicating Prp45 facilitates conformational rearrangements coupling U1 snRNP recognition to downstream assembly (complex A formation).\",\n      \"method\": \"RNA-seq, RT-qPCR, splicing reporters, chromatin immunoprecipitation (ChIP) along gene bodies for spliceosome components\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-based cotranscriptional assembly assay with defined genetic allele, multiple target genes examined, single lab\",\n      \"pmids\": [\"28701519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SNW1 acts as a transcriptional regulator of the NF-κB pathway by complexing with the NF-κB heterodimer in the nucleus; upon NF-κB activation, SNW1 detaches from its spliceosomal complex (with SNRNP200 and SNRNP220) and binds to the NF-κB transcriptional elongation partner p-TEFb, and is required for transcriptional elongation of NF-κB target genes IL-8 and TNF.\",\n      \"method\": \"Genome-wide RNAi screen, co-immunoprecipitation, siRNA knockdown with reporter and endogenous gene expression assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide screen hit validated by co-IP and functional knockdown with defined target genes, single lab\",\n      \"pmids\": [\"30397075\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SNW1 interacts with RBPJ to regulate Notch target gene expression in neuroblastoma; silencing RBPJ blocks SNW1-mediated Notch gene expression.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown of RBPJ, luciferase reporter assay for Notch targets\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP with limited functional follow-up, single lab\",\n      \"pmids\": [\"30642633\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SNW1 interacts with IKKγ (regulatory subunit of IκB kinase complex) to promote influenza A virus-induced activation of NF-κB and phosphorylation of TBK1, thereby increasing pro-inflammatory cytokines and IFN-β expression.\",\n      \"method\": \"Co-immunoprecipitation, SNW1 depletion/overexpression with reporter and ELISA assays, western blot for pathway activation\",\n      \"journal\": \"Microbes and infection\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP for IKKγ interaction, functional data from OE/KD, single lab\",\n      \"pmids\": [\"32805409\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"O-GlcNAcylation of SNW1 negatively regulates its ability to activate NF-κB p65 transcriptional activity; dexmedetomidine upregulates OGT-mediated O-GlcNAcylation of SNW1, reducing SNW1/NF-κB complex formation and inflammatory gene expression in neurons undergoing ischemia-reperfusion.\",\n      \"method\": \"Immunoprecipitation to detect O-GlcNAc on SNW1, luciferase reporter assay for NF-κB activity, OGT inhibitor experiments, ELISA for inflammatory factors, in vivo MCAO model\",\n      \"journal\": \"Journal of neuropathology and experimental neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct detection of PTM on SNW1 by IP, functional reporter assay, multiple in vitro and in vivo readouts, single lab\",\n      \"pmids\": [\"35818332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SNW1 promotes SRPK1 splicing by interacting with core spliceosome components NUDT21 and CPSF6, producing opposite expression changes in two distinct SRPK1 transcripts; SNW1's pro-metastatic effect in bladder cancer is dependent on SRPK1 protein expression.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, RT-PCR splicing assay, invasion/migration assays\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP and rescue experiments, single lab, limited mechanistic depth\",\n      \"pmids\": [\"41704767\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DSA (a monomer of Antrodia cinnamomea triterpenoids) binds SNW1 as a target protein; SNW1 promotes ALDH2 transcription and translation through synergistic interaction with the transcription factor RXR.\",\n      \"method\": \"Target fishing/cellular thermal shift assay for DSA-SNW1 binding, co-immunoprecipitation of SNW1-RXR, ALDH2 expression and activity assays\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — target engagement by thermal shift and co-IP, single lab with limited mechanistic follow-up\",\n      \"pmids\": [\"39591904\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The C-terminal region of yeast Prp45 (SNW1 ortholog) physically and functionally interacts with Lge1 (scaffold protein essential for the H2B ubiquitin ligase complex Bre1), stabilizing Lge1 and thereby promoting histone H2B ubiquitination; loss of the Prp45 C-terminus causes severe loss of H2B ubiquitination; the C-terminal IDR/helical domain from humans or plants can restore Lge1 stability and H2B ubiquitination in yeast.\",\n      \"method\": \"Genetic analysis (truncation alleles), proteomics (pulldown-MS), biochemical co-IP, western blot for H2B ubiquitination, cross-species complementation\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (genetics, proteomics, biochemistry, cross-species complementation) in a single preprint study\",\n      \"pmids\": [\"40667372\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Mutations in SNW1 impair its interactions with core spliceosomal proteins, causing defective RNA splicing (especially exon skipping) and reduced neural stem cell proliferation with increased apoptosis; disrupted alternative splicing of CENPE, MEF2C, and NRXN2 genes is observed in SNW1-depleted cerebral organoids and Drosophila.\",\n      \"method\": \"Patient mutation analysis, co-immunoprecipitation (mutant vs wild-type interactions), RNA-seq splicing analysis, Drosophila RNAi knockdown, human cerebral organoid model with siRNA depletion\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple model systems and orthogonal methods establishing splicing mechanism, though single study\",\n      \"pmids\": [\"40608414\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SNW1 is found in a chromatin-associated complex with SF3B1, P-TEFb, and the elongation/splicing factor HTATSF1; SF3B1 inhibition causes nuclear export of SNW1 (but not HTATSF1), contributing to decreased P-TEFb recruitment to chromatin.\",\n      \"method\": \"Co-immunoprecipitation, nuclear/cytoplasmic fractionation, chromatin immunoprecipitation after SF3B1 inhibitor treatment\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single preprint, Co-IP interaction and fractionation, limited functional follow-up specific to SNW1\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"SNW1 (also known as SKIP, NCoA-62, Prp45) is a dual-function nuclear protein that operates as both a spliceosome component and a transcriptional coactivator: within the spliceosome it makes dynamic contacts with the pre-mRNA branch-site region during catalytic activation, facilitates cotranscriptional recruitment of U2, U5, and NTC complexes, and enables splicing of specific introns (including those in sororin and APC2) required for sister chromatid cohesion and mitosis; in transcription it interacts directly with the VDR-RXR heterodimer at helix H10 (AF-2-independent) and with SRC coactivators to synergistically drive nuclear-receptor-mediated gene expression, complexes with NF-κB and p-TEFb to promote transcriptional elongation of inflammatory target genes, and its C-terminus stabilizes the Lge1 scaffold of the Bre1 H2B ubiquitin ligase, linking splicing to active transcription elongation through histone modification.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNW1 (SKIP/NCoA-62; yeast Prp45) is a dual-function nuclear protein that couples pre-mRNA splicing to transcriptional regulation [#9, #2]. As an essential spliceosome subunit, it associates directly with the core splicing machinery EFTUD2 (Snu114) and SNRNP200 (Brr2) through defined interaction surfaces [#10], makes dynamic contacts with nucleotides flanking the pre-mRNA branch site during catalytic activation [#11], and is required for early cotranscriptional recruitment of U2 and U5 snRNPs and the NTC, downstream of U1 recognition [#12]. Through this activity SNW1 enables splicing of specific introns in sororin and APC2 needed for sister chromatid cohesion and APC/C activity, with intron-less cDNA expression of these substrates rescuing cohesion defects in SNW1-depleted cells [#9]. In its transcriptional role, SNW1 acts as a coactivator that contacts the vitamin D receptor at an AF-2-independent surface of helix H10 and cooperates with SRC coactivators in a ternary complex with the VDR-RXR heterodimer to synergistically drive ligand-dependent transcription [#2, #3]. SNW1 also detaches from the spliceosome to bind the NF-\\u03baB heterodimer and the elongation factor p-TEFb, driving transcriptional elongation of inflammatory target genes such as IL-8 and TNF [#13], an activity negatively regulated by OGT-mediated O-GlcNAcylation of SNW1 [#16]. Developmentally, SNW1 is required for neural crest specification by setting a BMP-activity domain at the neural plate border upstream of BMP receptors [#8], and patient mutations that impair SNW1 contacts with core spliceosomal proteins cause exon-skipping defects and reduced neural stem cell proliferation in cerebral organoids and Drosophila [#20]. A C-terminal region of the protein additionally stabilizes the Lge1 scaffold of the Bre1 H2B ubiquitin ligase, linking SNW1 to histone H2B ubiquitination [#19].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established SNW1's first molecular role by showing it binds the vitamin D receptor and acts as a ligand-specific transcriptional coactivator, defining it as more than a generic factor.\",\n      \"evidence\": \"Yeast two-hybrid, GST pull-down, and reporter assays with VDR; parallel two-hybrid with the Ski oncoprotein and nuclear localization\",\n      \"pmids\": [\"9632709\", \"9569025\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not resolve the VDR interaction interface\", \"No structural model of the coactivator contact\", \"Functional role in splicing not yet recognized\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Defined how SNW1 cooperates with other coactivators, showing it engages a VDR surface distinct from SRC proteins to synergistically enhance nuclear-receptor transcription.\",\n      \"evidence\": \"Ternary complex binding, LXXLL peptide competition, co-IP, and reporter assays; later mapped to VDR helix H10 by point-mutant pull-downs\",\n      \"pmids\": [\"11514567\", \"12529369\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"AF-2-independent interface mapped functionally but not structurally\", \"Generalization beyond VDR to other nuclear receptors not established\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Connected SNW1 to conserved developmental signaling and splicing through model organisms, establishing both Notch-pathway requirement and an essential N-terminal SNW domain.\",\n      \"evidence\": \"Drosophila Bx42 RNAi with Notch genetic epistasis and target-gene readouts; yeast Prp45 domain complementation, GFP speckle localization, and Gal4-fusion reporter\",\n      \"pmids\": [\"12204255\", \"12359070\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether Notch effect is direct or via splicing not resolved\", \"Molecular function of the SNW domain undefined\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrated functional conservation of the splicing role by showing human SKIP rescues lethality of the yeast Prp45 deletion.\",\n      \"evidence\": \"Genetic complementation of prp45\\u0394 yeast with human SKIP\",\n      \"pmids\": [\"15194481\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Complementation shows conserved function but not mechanistic detail\", \"Substrate specificity in human cells not addressed\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Began to localize SNW1's action within the spliceosome by linking yeast Prp45 to the second-step helicase Prp22 and to splicing efficiency of non-consensus substrates.\",\n      \"evidence\": \"Synthetic lethality screen, Cwc2-pulldown complex purification, and in vivo splicing reporters with splice-site mutants\",\n      \"pmids\": [\"19016306\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect Prp22 interaction not fully resolved\", \"Human relevance of the Prp22 link untested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Placed SNW1 in vertebrate development by showing it patterns a BMP-activity domain upstream of BMP receptors to specify neural crest.\",\n      \"evidence\": \"Morpholino knockdown in Xenopus and zebrafish, pSmad1 immunostaining, BMP reporter transgenics, and rescue by targeted BMP overexpression\",\n      \"pmids\": [\"21358802\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether BMP regulation is via splicing of pathway components unknown\", \"Direct molecular target within the BMP axis not identified\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Resolved how SNW1 connects splicing to mitosis, identifying sororin and APC2 introns as critical substrates whose mis-splicing explains cohesion defects, and mapping direct contacts to EFTUD2 and SNRNP200.\",\n      \"evidence\": \"siRNA knockdown with RNA-seq splicing analysis, live-cell cohesion imaging, intron-less cDNA rescue; proteomics and reciprocal domain-mapped co-IP\",\n      \"pmids\": [\"25257309\", \"25450007\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why specific introns depend on SNW1 not mechanistically explained\", \"Structural basis of EFTUD2/SNRNP200 contacts unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the step at which SNW1 acts in spliceosome assembly, showing yeast Prp45 contacts the branch site during catalytic activation and is needed for cotranscriptional U2/U5/NTC recruitment after U1 recognition.\",\n      \"evidence\": \"UV crosslinking of purified Bact/B*/C complexes with mass spectrometry; ChIP along gene bodies for spliceosome components with the prp45(1-169) allele\",\n      \"pmids\": [\"26393790\", \"28701519\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Human conservation of these assembly-stage roles not directly tested\", \"How Prp45 drives the conformational coupling mechanistically unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed a regulated switch from spliceosome to transcription, with SNW1 detaching from the spliceosome to bind NF-\\u03baB and p-TEFb and drive elongation of inflammatory genes, and engaging RBPJ for Notch targets.\",\n      \"evidence\": \"Genome-wide RNAi screen, co-IP, and knockdown with target-gene expression for NF-\\u03baB; co-IP and reporter assays for RBPJ in neuroblastoma\",\n      \"pmids\": [\"30397075\", \"30642633\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Trigger and kinetics of the spliceosome-to-NF-\\u03baB switch undefined\", \"RBPJ interaction rests on a single Co-IP without reciprocal validation\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended SNW1's NF-\\u03baB role to innate antiviral signaling, showing it engages IKK\\u03b3 to promote influenza-induced NF-\\u03baB and TBK1 activation.\",\n      \"evidence\": \"Co-IP, depletion/overexpression with reporter and ELISA, and western blot for pathway activation\",\n      \"pmids\": [\"32805409\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"IKK\\u03b3 interaction from a single Co-IP without reciprocal confirmation\", \"Direct vs indirect engagement unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified a post-translational control point, showing O-GlcNAcylation of SNW1 suppresses its NF-\\u03baB-activating function.\",\n      \"evidence\": \"IP-based detection of O-GlcNAc on SNW1, NF-\\u03baB reporter, OGT-inhibitor experiments, ELISA, and an in vivo MCAO model\",\n      \"pmids\": [\"35818332\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Modified residue(s) on SNW1 not mapped\", \"Whether O-GlcNAcylation also affects splicing function untested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Broadened the splicing repertoire and disease relevance, linking SNW1 to SRPK1 transcript choice via NUDT21/CPSF6 and to a chromatin complex with SF3B1, P-TEFb, and HTATSF1.\",\n      \"evidence\": \"Co-IP, knockdown, RT-PCR splicing and invasion assays for SRPK1; co-IP, fractionation and ChIP after SF3B1 inhibition (preprint); DSA target-engagement and SNW1-RXR co-IP for ALDH2\",\n      \"pmids\": [\"41704767\", \"39591904\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"SRPK1 and ALDH2 mechanisms rest on single-lab Co-IP/rescue\", \"SF3B1/P-TEFb complex evidence is a preprint with limited SNW1-specific follow-up\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established a human disease link and a new C-terminal function, showing pathogenic SNW1 mutations disrupt spliceosomal contacts and exon inclusion to impair neurodevelopment, while the C-terminus stabilizes the Lge1 scaffold to promote H2B ubiquitination.\",\n      \"evidence\": \"Patient mutation analysis, mutant-vs-WT co-IP, RNA-seq, Drosophila RNAi and cerebral organoid models; truncation genetics, pulldown-MS, H2B-ubiquitination western blot and cross-species complementation (preprint)\",\n      \"pmids\": [\"40608414\", \"40667372\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Genotype-phenotype spectrum of SNW1 mutations not fully delineated\", \"Lge1/Bre1 link demonstrated in yeast with cross-species rescue but not in human cells\", \"How splicing and H2B-ubiquitination roles are coordinated unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SNW1 dynamically partitions between its spliceosomal and transcriptional/chromatin roles, and what governs substrate intron selectivity, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of SNW1 within the human spliceosome\", \"Signals controlling the spliceosome-to-transcription switch unknown\", \"Rules determining which introns require SNW1 undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 2, 13]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [9, 11, 12]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 10, 19]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [5, 13]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [21]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [9, 11, 12]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [2, 13]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [8, 20]}\n    ],\n    \"complexes\": [\"spliceosome\", \"VDR-RXR-SRC coactivator complex\", \"NF-\\u03baB/p-TEFb elongation complex\"],\n    \"partners\": [\"VDR\", \"RXR\", \"EFTUD2\", \"SNRNP200\", \"RBPJ\", \"IKBKG\", \"SF3B1\", \"Lge1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}