IWS1 Gene

Name	IWS1 homolog (S. cerevisiae)
Description	Involved in regulation of mRNA export from nucleus; regulation of mRNA processing; and transcription elongation-coupled chromatin remodeling. Located in nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IWS1 is an essential RNA polymerase II–associated factor that functions as a molecular scaffold during transcription elongation by mediating the coupling of nascent RNA synthesis with mRNA processing, splicing, and export. In mammalian cells, IWS1 interacts with the elongation factor Spt6 to facilitate the co‐transcriptional recruitment of mRNA export factors such as REF1/Aly and to promote proper processing of transcripts, as evidenced by defects in splicing and nuclear mRNA retention when IWS1 or its associated partners are perturbed."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, IWS1 plays a pivotal role in establishing specific histone modification patterns by recruiting the histone methyltransferase SETD2 (also known as HYPB), which catalyzes H3K36 trimethylation across actively transcribed regions. This modification is crucial not only for proper splicing but also for creating a chromatin environment that sustains productive elongation and ensures genome integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n IWS1 function is further modulated by its phosphorylation status. Phosphorylation by Akt isoforms, particularly Akt1 and Akt3, governs alternative splicing decisions, as illustrated by the shift toward tumorigenic FGFR2 isoforms in cancer cells. This post‐translational modification underlines an Akt–IWS1 signaling axis that influences oncogenic RNA processing and tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of viral infections, IWS1 is implicated in the control of HIV-1 latency. By forming a complex with LEDGF/p75 and Spt6, IWS1 helps maintain the silent chromatin state at the integrated provirus and supports proper histone occupancy at the HIV promoter. Interference with this complex results in reactivation of viral expression, highlighting its importance for postintegration silencing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, genetic studies in mice have demonstrated that IWS1 is indispensable for early development, with its ablation leading to pre-implantation lethality and defects in embryonic genome activation and lineage specification. In embryonic cells, IWS1, together with Spt6, regulates pre-mRNA splicing, mRNA export, and the establishment of correct histone methylation patterns, a process further modulated by the Pi3k/Akt pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sunnie M Yoh, Helen Cho, Loni Pickle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1503107"}], "href": "https://doi.org/10.1101/gad.1503107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17234882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17234882"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sunnie M Yoh, Joseph S Lucas, Katherine A Jones "}, {"type": "b", "children": [{"type": "t", "text": "The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1720008"}], "href": "https://doi.org/10.1101/gad.1720008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19141475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19141475"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ioannis Sanidas, Christos Polytarchou, Maria Hatziapostolou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphoproteomics screen reveals akt isoform-specific signals linking RNA processing to lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2013.12.018"}], "href": "https://doi.org/10.1016/j.molcel.2013.12.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24462114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24462114"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Unknown Authors "}, {"type": "b", "children": [{"type": "t", "text": "AKT isoform-specific signals regulate RNA processing in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-RW2014-028"}], "href": "https://doi.org/10.1158/2159-8290.CD-RW2014-028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24596211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24596211"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Annabelle Gérard, Emmanuel Ségéral, Monica Naughtin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The integrase cofactor LEDGF/p75 associates with Iws1 and Spt6 for postintegration silencing of HIV-1 gene expression in latently infected cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2014.12.002"}], "href": "https://doi.org/10.1016/j.chom.2014.12.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25590759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25590759"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Arturo Orlacchio, Aaron E Stark, Claudia Foray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic ablation of interacting with Spt6 (Iws1) causes early embryonic lethality."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0201030"}], "href": "https://doi.org/10.1371/journal.pone.0201030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30208029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30208029"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Reza K Oqani, Tao Lin, Jae Eun Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iws1 and Spt6 Regulate Trimethylation of Histone H3 on Lysine 36 through Akt Signaling and are Essential for Mouse Embryonic Genome Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-40358-3"}], "href": "https://doi.org/10.1038/s41598-019-40358-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30846735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30846735"}]}]}]}
Proteins	IWS1_HUMAN
NCBI Gene ID	55677
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IWS1 has 5,551 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for IWS1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IWS1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IWS1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of IWS1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of IWS1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of IWS1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of IWS1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IWS1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IWS1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of IWS1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of IWS1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IWS1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IWS1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IWS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of IWS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing IWS1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IWS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing IWS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing IWS1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing IWS1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with IWS1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with IWS1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of IWS1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IWS1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with IWS1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with IWS1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by IWS1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with IWS1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with IWS1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with IWS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IWS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at IWS1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IWS1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of IWS1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing IWS1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with IWS1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing IWS1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of IWS1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of IWS1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of IWS1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of IWS1 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
	GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations	transcription factor perturbations changing expression of IWS1 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.