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    WAPL WAPL cohesin release factor [ Homo sapiens (human) ]

    Gene ID: 23063, updated on 10-Dec-2024

    Summary

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    Official Symbol
    WAPLprovided by HGNC
    Official Full Name
    WAPL cohesin release factorprovided by HGNC
    Primary source
    HGNC:HGNC:23293
    See related
    Ensembl:ENSG00000062650 MIM:610754; AllianceGenome:HGNC:23293
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FOE; WAPAL; KIAA0261
    Summary
    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, Dec 2024]
    Expression
    Ubiquitous expression in testis (RPKM 17.0), lymph node (RPKM 9.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See WAPL in Genome Data Viewer
    Location:
    10q23.2
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (86435256..86521792, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (87315788..87405903, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (88195013..88281549, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene glutamate ionotropic receptor delta type subunit 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88024064-88024564 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_17795 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88051161-88051975 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88051976-88052790 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88057946-88058446 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88089455-88090419 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88091551-88092052 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88092053-88092552 Neighboring gene Sharpr-MPRA regulatory region 9256 Neighboring gene microRNA 346 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88122633-88123146 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88123147-88123660 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2556 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2560 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2559 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2558 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2557 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88136831-88137373 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2563 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3683 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3684 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3685 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88159531-88160524 Neighboring gene uncharacterized LOC124902473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88162319-88162871 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:88160525-88161518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3688 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3689 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:88183258-88184012 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_17841 Neighboring gene Sharpr-MPRA regulatory region 10398 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:88221644-88222250 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3691 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88263469-88263969 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2569 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2570 Neighboring gene RNA, U6 small nuclear 780, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr10:88288988-88289146 Neighboring gene uncharacterized LOC105378408 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2571 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:88295813-88296362 Neighboring gene uncharacterized LOC105378407 Neighboring gene WAPL divergent transcript

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. WAPL-Dependent Repair of Damaged DNA Replication Forks Underlies Oncogene-Induced Loss of Sister Chromatid Cohesion. Benedict B, et al. Dev Cell, 2020 Mar 23. PMID 32084359
    2. Identification and cloning of a novel chromatin-associated protein partner of Epstein-Barr nuclear protein 2. Kwiatkowski BA, et al. Exp Cell Res, 2004 Oct 15. PMID 15383329
    3. Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection. Masamsetti VP, et al. Nat Commun, 2019 Sep 17. PMID 31530811, Free PMC Article
    4. WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7. Kumagai K, et al. Oncogene, 2021 May. PMID 33947962, Free PMC Article
    5. Unscheduled overexpression of human WAPL promotes chromosomal instability. Ohbayashi T, et al. Biochem Biophys Res Commun, 2007 May 11. PMID 17382297

    See all (121) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A Mediator-cohesin axis controls heterochromatin domain formation.
      Title: A Mediator-cohesin axis controls heterochromatin domain formation.
    2. WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7.
      Title: WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7.
    3. ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin(STAG1) from WAPL.
      Title: ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin(STAG1) from WAPL.
    4. WAPL-Dependent Repair of Damaged DNA Replication Forks Underlies Oncogene-Induced Loss of Sister Chromatid Cohesion.
      Title: WAPL-Dependent Repair of Damaged DNA Replication Forks Underlies Oncogene-Induced Loss of Sister Chromatid Cohesion.
    5. Absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin were measured by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells.
      Title: Absolute quantification of cohesin, CTCF and their regulators in human cells.
    6. In p53-compromised cells we find that lethal replication stress confers WAPL-dependent centromere cohesion defects that maintain spindle assembly checkpoint-dependent mitotic arrest in the same cell cycle.
      Title: Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection.
    7. Rec8-Stag3 cohesin is shown to be susceptible to Wapl-dependent ring opening and sororin-mediated protection.
      Title: Studying meiotic cohesin in somatic cells reveals that Rec8-containing cohesin requires Stag3 to function and is regulated by Wapl and sororin.
    8. We provide evidence that the underlying mechanism involves the viral NS3/4 protease and the cohesin regulator, WAPL
      Title: Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions.
    9. The results indicate a kinase-dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis.
      Title: A kinase-dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion.
    10. The results show that cohesin has an essential genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA by WAPL.
      Title: Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
    EBI GWAS Catalog
    Genome-wide association study of periodontal pathogen colonization.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP-dependent protein-DNA unloader activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic sister chromatid segregation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of chromatin binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of sister chromatid cohesion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization to chromatin IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in chromosome TAS
    Traceable Author Statement
    more info
    		  
    located_in chromosome, centromeric region TAS
    Traceable Author Statement
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in intercellular bridge IDA
    Inferred from Direct Assay
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitotic spindle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    wings apart-like protein homolog
    Names
    friend of EBNA2 (Epstein-Barr virus nuclear protein 2)
    friend of EBNA2 protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001318328.2 → NP_001305257.1  wings apart-like protein homolog isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate, in-frame splice site in the 5' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
      Source sequence(s)
      AL731569, AL844892
      UniProtKB/TrEMBL
      B2RTX8
      Conserved Domains (1) summary
      pfam07814
      Location:632 → 992
      WAPL; Wings apart-like protein regulation of heterochromatin

    2. NM_015045.5 → NP_055860.1  wings apart-like protein homolog isoform 1

      See identical proteins and their annotated locations for NP_055860.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AL731569, AL844892
      Consensus CDS
      CCDS7375.1
      UniProtKB/Swiss-Prot
      A7E2B5, Q5VSK5, Q7Z5K2, Q8IX10, Q92549
      Related
      ENSP00000298767.4, ENST00000298767.10
      Conserved Domains (1) summary
      pfam07814
      Location:638 → 998
      WAPL; Wings apart-like protein regulation of heterochromatin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      86435256..86521792 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      87315788..87405903 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q7Z5K2.1 GenPept UniProtKB/Swiss-Prot:Q7Z5K2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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