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    SYNE4 spectrin repeat containing nuclear envelope family member 4 [ Homo sapiens (human) ]

    Gene ID: 163183, updated on 11-Apr-2024

    Summary

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    Official Symbol
    SYNE4provided by HGNC
    Official Full Name
    spectrin repeat containing nuclear envelope family member 4provided by HGNC
    Primary source
    HGNC:HGNC:26703
    See related
    Ensembl:ENSG00000181392 MIM:615535; AllianceGenome:HGNC:26703
    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
    KASH4; Nesp4; DFNB76; C19orf46
    Summary
    This gene is a member of the nesprin family of genes, that encode KASH (Klarsicht, Anc-1, Syne Homology) domain-containing proteins. In addition to the KASH domain, this protein also contains a coiled-coil and leucine zipper region, a spectrin repeat, and a kinesin-1 binding region. This protein localizes to the outer nuclear membrane, and is part of the linker of nucleoskeleton and cytoskeleton (LINC) complex in the nuclear envelope. LINC complexes are formed by SUN (Sad1, UNC-84)-KASH pairs, and are thought to mechanically couple nuclear components to the cytoskeleton. Mutations in this gene have been associated with progressive high-frequency hearing loss. The absence of this protein in mice also caused hearing loss, and changes in hair cell morphology in the ears. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
    Expression
    Broad expression in prostate (RPKM 6.3), thyroid (RPKM 3.5) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    19q13.12
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (36003307..36008813, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (38549106..38554612, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (36494209..36499715, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372383 Neighboring gene Sharpr-MPRA regulatory region 3529 Neighboring gene Sharpr-MPRA regulatory region 1826 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10543 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10544 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14510 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:36453209-36453373 Neighboring gene MPRA-validated peak3453 silencer Neighboring gene MPRA-validated peak3454 silencer Neighboring gene MPRA-validated peak3455 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14511 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:36485053-36485552 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14513 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10545 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10546 Neighboring gene succinate dehydrogenase complex assembly factor 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:36498887-36499428 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:36499429-36499968 Neighboring gene uncharacterized LOC101927572 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14514 Neighboring gene alkB homolog 6 Neighboring gene CAP-Gly domain containing linker protein 3

    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
    • 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. The LINC complex is essential for hearing. Horn HF, et al. J Clin Invest, 2013 Feb. PMID 23348741, Free PMC Article
    2. Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization. Roux KJ, et al. Proc Natl Acad Sci U S A, 2009 Feb 17. PMID 19164528, Free PMC Article
    3. Genetic Hearing Loss Overview. Adam MP, et al. , 1993. PMID 20301607
    4. Widespread macromolecular interaction perturbations in human genetic disorders. Sahni N, et al. Cell, 2015 Apr 23. PMID 25910212, Free PMC Article
    5. Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Yang X, et al. Cell, 2016 Feb 11. PMID 26871637, Free PMC Article

    See all (17) citations in PubMed

    GeneRIFs: Gene References Into Functions

    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
    Autosomal recessive nonsyndromic hearing loss 76
    MedGen: C3147083 OMIM: 615540 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    • FLJ36445

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in establishment of epithelial cell apical/basal polarity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in establishment of epithelial cell apical/basal polarity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    part_of meiotic nuclear membrane microtubule tethering complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nuclear outer membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nuclear outer membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    nesprin-4
    Names
    KASH domain-containing protein 4
    deafness, autosomal recessive 76
    nuclear envelope spectrin repeat protein 4

    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_042831.1 RefSeqGene

      Range
      4981..10487
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1385

    mRNA and Protein(s)

    1. NM_001039876.3 → NP_001034965.1  nesprin-4 isoform 1

      See identical proteins and their annotated locations for NP_001034965.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AA991508, AC002116, AF038458, BC038360, BC052573
      Consensus CDS
      CCDS42553.1
      UniProtKB/Swiss-Prot
      A8MRS0, A8MYE3, Q7Z7L3, Q8N205
      Related
      ENSP00000316130.3, ENST00000324444.9
      Conserved Domains (1) summary
      pfam10541
      Location:368 → 404
      KASH; Nuclear envelope localization domain

    2. NM_001297735.3 → NP_001284664.1  nesprin-4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two consecutive, alternate in-frame exons in the coding region, compared to variant 1. It encodes isoform 2, which lacks an internal segment and is shorter, compared to isoform 1.
      Source sequence(s)
      AA991508, AC002116, AK093764, BC038360, BC052573
      Consensus CDS
      CCDS77285.1
      UniProtKB/Swiss-Prot
      Q8N205
      Related
      ENSP00000343152.5, ENST00000340477.9
      Conserved Domains (1) summary
      pfam10541
      Location:255 → 291
      KASH; Nuclear envelope localization domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      36003307..36008813 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047438350.1 → XP_047294306.1  nesprin-4 isoform X7

    2. XM_047438347.1 → XP_047294303.1  nesprin-4 isoform X4

    3. XM_047438345.1 → XP_047294301.1  nesprin-4 isoform X2

    4. XM_047438351.1 → XP_047294307.1  nesprin-4 isoform X8

    5. XM_047438344.1 → XP_047294300.1  nesprin-4 isoform X1

    6. XM_047438349.1 → XP_047294305.1  nesprin-4 isoform X6

    7. XM_047438346.1 → XP_047294302.1  nesprin-4 isoform X3

      Related
      ENSP00000422716.1, ENST00000490730.1

    8. XM_047438348.1 → XP_047294304.1  nesprin-4 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      38549106..38554612 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054320091.1 → XP_054176066.1  nesprin-4 isoform X7

    2. XM_054320088.1 → XP_054176063.1  nesprin-4 isoform X4

    3. XM_054320086.1 → XP_054176061.1  nesprin-4 isoform X2

    4. XM_054320092.1 → XP_054176067.1  nesprin-4 isoform X8

    5. XM_054320085.1 → XP_054176060.1  nesprin-4 isoform X1

    6. XM_054320090.1 → XP_054176065.1  nesprin-4 isoform X6

    7. XM_054320087.1 → XP_054176062.1  nesprin-4 isoform X3

    8. XM_054320089.1 → XP_054176064.1  nesprin-4 isoform X5

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_153233.1: Suppressed sequence

      Description
      NM_153233.1: This RefSeq was permanently suppressed because it is a nonsense-mediated decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N205.2 GenPept UniProtKB/Swiss-Prot:Q8N205

    Gene LinkOut

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

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