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    WAC WW domain containing adaptor with coiled-coil [ Homo sapiens (human) ]

    Gene ID: 51322, updated on 2-Nov-2024

    Summary

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    Official Symbol
    WACprovided by HGNC
    Official Full Name
    WW domain containing adaptor with coiled-coilprovided by HGNC
    Primary source
    HGNC:HGNC:17327
    See related
    Ensembl:ENSG00000095787 MIM:615049; AllianceGenome:HGNC:17327
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    Wwp4; DESSH; BM-016; PRO1741
    Summary
    The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]
    Expression
    Ubiquitous expression in bone marrow (RPKM 29.5), thyroid (RPKM 26.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See WAC in Genome Data Viewer
    Location:
    10p12.1; 10p12.1-p11.2
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (28532779..28623112)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (28563354..28653650)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (28821708..28912041)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2652 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:28733718-28733938 Neighboring gene RN7SK pseudogene 39 Neighboring gene NANOG hESC enhancer GRCh37_chr10:28782091-28782660 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:28821447-28822130 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2253 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2254 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2255 Neighboring gene WAC antisense RNA 1 (head to head) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2256 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:28943960-28944522 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:28946775-28947338 Neighboring gene RNA, U4atac small nuclear 6, pseudogene Neighboring gene TP53RK binding protein pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. WAC-Related Intellectual Disability. Adam MP, et al. , 1993. PMID 29190062
    2. A de novo 10p11.23-p12.1 deletion recapitulates the phenotype observed in WAC mutations and strengthens the role of WAC in intellectual disability and behavior disorders. Abdelhedi F, et al. Am J Med Genet A, 2016 Jul. PMID 27119754
    3. A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES). Leonardi E, et al. Genes (Basel), 2020 Mar 24. PMID 32214004, Free PMC Article
    4. Clinical and molecular characterization of five new individuals with WAC-related intellectual disability: Evidence of pathogenicity for a novel splicing variant. Morales JA, et al. Am J Med Genet A, 2022 May. PMID 35018708
    5. Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder. Tammimies K, et al. JAMA, 2015 Sep 1. PMID 26325558

    See all (86) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Clinical and molecular characterization of five new individuals with WAC-related intellectual disability: Evidence of pathogenicity for a novel splicing variant.
      Title: Clinical and molecular characterization of five new individuals with WAC-related intellectual disability: Evidence of pathogenicity for a novel splicing variant.
    2. WAC, a novel GBM tumor suppressor, induces GBM cell apoptosis and promotes autophagy.
      Title: WAC, a novel GBM tumor suppressor, induces GBM cell apoptosis and promotes autophagy.
    3. Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript.
      Title: Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript.
    4. Self-limited focal epilepsy and childhood apraxia of speech with WAC pathogenic variants.
      Title: Self-limited focal epilepsy and childhood apraxia of speech with WAC pathogenic variants.
    5. A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES).
      Title: A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES).
    6. these results indicate an important role for WAC in promoting Plk1 activation and the timely entry into mitosis.
      Title: WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry.
    7. Our observation allows us to redefine the smallest region of overlap among patients reported so far, with a size of 80 Kb and which contains only the WAC gene. These findings strengthen the hypothesis that haploinsufficency of WAC gene might be likely responsible for intellectual disability and behavior disorders.
      Title: A de novo 10p11.23-p12.1 deletion recapitulates the phenotype observed in WAC mutations and strengthens the role of WAC in intellectual disability and behavior disorders.
    8. De novo WAC loss-of-function mutations were identified through exome sequencing of individuals with unexplained intellectual disability.
      Title: De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila.
    9. WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome
      Title: WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome.
    10. Data show that WAC directly binds to GM130 and that this binding is required for autophagosome formation through interacting with GABARAP regulating its subcellular localization.
      Title: Activation of ULK Kinase and Autophagy by GABARAP Trafficking from the Centrosome Is Regulated by WAC and GM130.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Associated conditions

    Description Tests
    DeSanto-Shinawi syndrome due to WAC point mutation
    MedGen: C5681129 OMIM: 616708 GeneReviews: WAC-Related Intellectual Disability
    		not available

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2018-02-28)

    ClinGen Genome Curation PagePubMed
    Triplosensitivity

    No evidence available (Last evaluated 2018-02-28)

    ClinGen Genome Curation Page

    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

    Clone Names

    • MGC10753

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA polymerase II complex binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II complex binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables chromatin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables chromatin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in chromatin remodeling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitotic G1 DNA damage checkpoint signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of TORC1 signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of macroautophagy IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of autophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in nuclear speck IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of spliceosomal complex IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    WW domain-containing adapter protein with coiled-coil

    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.

    Genomic

    1. NG_046603.1 RefSeqGene

      Range
      5531..95525
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_016628.5 → NP_057712.2  WW domain-containing adapter protein with coiled-coil isoform 1

      See identical proteins and their annotated locations for NP_057712.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AK290174, AL161936, AL358234, CB143386
      Consensus CDS
      CCDS7159.1
      UniProtKB/Swiss-Prot
      A8K2A9, C9JBT9, D3DRW5, D3DRW6, D3DRW7, Q53EN9, Q5JU75, Q5JU77, Q5VXK0, Q5VXK2, Q8TCK1, Q96DP3, Q96FW6, Q96JI3, Q9BTA9
      UniProtKB/TrEMBL
      A0A8V8TQV5
      Related
      ENSP00000346986.4, ENST00000354911.9
      Conserved Domains (1) summary
      pfam00397
      Location:133 → 160
      WW; WW domain

    2. NM_100264.3 → NP_567822.1  WW domain-containing adapter protein with coiled-coil isoform 2

      See identical proteins and their annotated locations for NP_567822.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate 5' terminal exon, and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) is shorter at the N-terminus, comapared to isoform 1.
      Source sequence(s)
      AA424883, AK225846, AL161936
      Consensus CDS
      CCDS7161.1
      UniProtKB/TrEMBL
      A0A8V8TQV5
      Related
      ENSP00000364816.3, ENST00000375664.8
      Conserved Domains (2) summary
      pfam00397
      Location:88 → 115
      WW; WW domain
      cl26464
      Location:190 → 466
      Atrophin-1; Atrophin-1 family

    3. NM_100486.4 → NP_567823.1  WW domain-containing adapter protein with coiled-coil isoform 3

      See identical proteins and their annotated locations for NP_567823.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks a coding exon but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AL161936, AL358234, BC010356, BI226998, CB143386
      Consensus CDS
      CCDS7160.1
      UniProtKB/TrEMBL
      A0A0A0MRT2
      Related
      ENSP00000311106.4, ENST00000347934.8
      Conserved Domains (1) summary
      pfam00397
      Location:133 → 160
      WW; WW domain

    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
      28532779..28623112
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047425320.1 → XP_047281276.1  WW domain-containing adapter protein with coiled-coil isoform X5

      Related
      ENSP00000506445.1, ENST00000679428.1

    2. XM_047425315.1 → XP_047281271.1  WW domain-containing adapter protein with coiled-coil isoform X5

    3. XM_047425321.1 → XP_047281277.1  WW domain-containing adapter protein with coiled-coil isoform X5

    4. XM_047425310.1 → XP_047281266.1  WW domain-containing adapter protein with coiled-coil isoform X1

    5. XM_047425311.1 → XP_047281267.1  WW domain-containing adapter protein with coiled-coil isoform X2

    6. XM_047425318.1 → XP_047281274.1  WW domain-containing adapter protein with coiled-coil isoform X6

    7. XM_047425316.1 → XP_047281272.1  WW domain-containing adapter protein with coiled-coil isoform X5

    8. XM_047425312.1 → XP_047281268.1  WW domain-containing adapter protein with coiled-coil isoform X3

    9. XM_047425313.1 → XP_047281269.1  WW domain-containing adapter protein with coiled-coil isoform X4

    10. XM_047425319.1 → XP_047281275.1  WW domain-containing adapter protein with coiled-coil isoform X7

    11. XM_047425309.1 → XP_047281265.1  WW domain-containing adapter protein with coiled-coil isoform X9

    12. XM_047425314.1 → XP_047281270.1  WW domain-containing adapter protein with coiled-coil isoform X10

    13. XM_047425322.1 → XP_047281278.1  WW domain-containing adapter protein with coiled-coil isoform X8

    14. XM_047425317.1 → XP_047281273.1  WW domain-containing adapter protein with coiled-coil isoform X5

      Related
      ENSP00000506624.1, ENST00000679398.1

    RNA

    1. XR_007061967.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      28563354..28653650
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054366042.1 → XP_054222017.1  WW domain-containing adapter protein with coiled-coil isoform X5

    2. XM_054366036.1 → XP_054222011.1  WW domain-containing adapter protein with coiled-coil isoform X5

    3. XM_054366043.1 → XP_054222018.1  WW domain-containing adapter protein with coiled-coil isoform X5

    4. XM_054366032.1 → XP_054222007.1  WW domain-containing adapter protein with coiled-coil isoform X1

    5. XM_054366033.1 → XP_054222008.1  WW domain-containing adapter protein with coiled-coil isoform X2

    6. XM_054366038.1 → XP_054222013.1  WW domain-containing adapter protein with coiled-coil isoform X11

    7. XM_054366039.1 → XP_054222014.1  WW domain-containing adapter protein with coiled-coil isoform X6

    8. XM_054366037.1 → XP_054222012.1  WW domain-containing adapter protein with coiled-coil isoform X5

    9. XM_054366034.1 → XP_054222009.1  WW domain-containing adapter protein with coiled-coil isoform X3

    10. XM_054366035.1 → XP_054222010.1  WW domain-containing adapter protein with coiled-coil isoform X4

    11. XM_054366040.1 → XP_054222015.1  WW domain-containing adapter protein with coiled-coil isoform X7

    12. XM_054366044.1 → XP_054222019.1  WW domain-containing adapter protein with coiled-coil isoform X8

    13. XM_054366041.1 → XP_054222016.1  WW domain-containing adapter protein with coiled-coil isoform X12

    RNA

    1. XR_008488219.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BTA9.3 GenPept UniProtKB/Swiss-Prot:Q9BTA9

    Gene LinkOut

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