| Name | WAPL cohesin release factor |
| Description | Enables ATP-dependent protein-DNA unloader activity. Involved in several processes, including mitotic sister chromatid segregation; negative regulation of DNA replication; and negative regulation of sister chromatid cohesion. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCohesin complexes are essential architectural components of the genome that form chromatin loops and topologically associated domains, processes that are critically modulated by the dynamic loading and unloading of cohesin. WAPL functions as a DNA release factor by promoting the dissociation of cohesin from chromatin, thereby restricting the processive enlargement of chromatin loops and preventing aberrant looping—such as contacts between incorrectly oriented CTCF sites—that could compromise proper genome organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDuring mitosis, the role of WAPL becomes even more pivotal as it facilitates the removal of cohesin from chromosomes during prophase, a critical step for ensuring timely sister chromatid resolution and accurate chromosome segregation. Depletion of WAPL leads to prolonged cohesin residence on chromatin, delays in chromatid separation, and subsequent mitotic errors. Structural studies further reveal that WAPL, together with binding partners such as PDS5, acts as a negative regulator of cohesin stability on DNA, thus contributing to proper chromosomal condensation and the fidelity of cell division."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent evidence also indicates that selective modulation of cohesin’s chromatin residence involves protective mechanisms against WAPL-mediated release—for instance, through acetylation of cohesin subunits (such as cohesin‐STAG1) that renders them resistant to WAPL activity. This interplay permits the formation of long-lived chromatin loops and nested loop extrusion events, integrating WAPL’s release function with the stabilization of higher-order chromatin architecture essential for proper gene regulation and genome integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Judith H I Haarhuis, Robin H van der Weide, Vincent A Blomen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2017.04.013"}], "href": "https://doi.org/10.1016/j.cell.2017.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28475897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28475897"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gordana Wutz, Csilla Várnai, Kota Nagasaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201798004"}], "href": "https://doi.org/10.15252/embj.201798004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29217591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29217591"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Stephanie Kueng, Björn Hegemann, Beate H Peters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wapl controls the dynamic association of cohesin with chromatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.09.040"}], "href": "https://doi.org/10.1016/j.cell.2006.09.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17113138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17113138"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nan Wu, Xiangduo Kong, Zhejian Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.193615.112"}], "href": "https://doi.org/10.1101/gad.193615.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751501"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Judith H I Haarhuis, Ahmed M O Elbatsh, Bram van den Broek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WAPL-mediated removal of cohesin protects against segregation errors and aneuploidy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2013.09.003"}], "href": "https://doi.org/10.1016/j.cub.2013.09.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24055153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24055153"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gordana Wutz, Rene Ladurner, Brian Glenn St Hilaire, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "STAG1"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " from WAPL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.52091"}], "href": "https://doi.org/10.7554/eLife.52091"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32065581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32065581"}]}]}]}
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| NCBI Gene ID | 23063 |
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| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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WAPL has 3,025 functional associations with biological entities spanning 5 categories (chemical, functional term, phrase or reference, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA) extracted from 44 datasets.
Click the + buttons to view associations for WAPL from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of WAPL gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of WAPL gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Proteomics | Cell lines associated with WAPL protein from the CCLE Cell Line Proteomics dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with WAPL gene from the CellMarker Gene-Cell Type Associations dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of WAPL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of WAPL gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing WAPL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 | cellular components containing WAPL 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 2025 | cellular components co-occuring with WAPL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by WAPL gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with WAPL 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 WAPL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with WAPL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving WAPL gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving WAPL gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing WAPL protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing WAPL protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of WAPL gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with WAPL gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of WAPL gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of WAPL gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| KEGG Pathways 2026 | pathways involving WAPL protein from the KEGG Pathways 2026 dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of WAPL gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of WAPL gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by WAPL gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of WAPL gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of WAPL gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving WAPL protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving WAPL protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2024 | pathways involving WAPL protein from the Reactome Pathways 2024 dataset. | |
| Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of WAPL gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of WAPL gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of WAPL gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of WAPL gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of WAPL gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of WAPL gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sanger Dependency Map Cancer Cell Line Proteomics | cell lines associated with WAPL protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset. | |
| Sci-Plex Drug Perturbation Signatures | drug perturbations changing expression of WAPL gene from the Sci-Plex Drug Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of WAPL gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| Tahoe Therapeutics Tahoe 100M Perturbation Atlas | drug perturbations changing expression of WAPL gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of WAPL protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of WAPL protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with WAPL protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving WAPL protein from the WikiPathways Pathways 2024 dataset. | |
