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    NEK4 NIMA related kinase 4 [ Homo sapiens (human) ]

    Gene ID: 6787, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NEK4provided by HGNC
    Official Full Name
    NIMA related kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:11399
    See related
    Ensembl:ENSG00000114904 MIM:601959; AllianceGenome:HGNC:11399
    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
    NRK2; STK2; pp12301
    Summary
    The protein encoded by this gene is a serine/threonine protein kinase required for normal entry into replicative senescence. The encoded protein also is involved in cell cycle arrest in response to double-stranded DNA damage. Finally, this protein plays a role in maintaining cilium integrity, and defects in this gene have been associated with ciliopathies. [provided by RefSeq, Jan 2017]
    Expression
    Broad expression in testis (RPKM 13.9), thyroid (RPKM 5.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NEK4 in Genome Data Viewer
    Location:
    3p21.1
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (52708444..52770940, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (52741355..52803847, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52742460..52804956, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene G protein nucleolar 3 Neighboring gene small nucleolar RNA, C/D box 69 Neighboring gene glycosyltransferase 8 domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14451 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19946 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14452 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:52749367-52749954 Neighboring gene signal peptidase complex subunit 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:52765581-52766780 Neighboring gene zinc finger protein 610 pseudogene Neighboring gene adenylate kinase 3 pseudogene Neighboring gene AK3 pseudogene 7 Neighboring gene AKTIP pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:52804733-52805250 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:52812248-52813447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19948 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:52828410-52829299 Neighboring gene inter-alpha-trypsin inhibitor heavy chain 3 Neighboring gene uncharacterized LOC124906240

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach. Zhang C, et al. Schizophr Bull, 2024 Aug 27. PMID 38869147,
    2. [Basic factors influencing gene expressivity and penetrance in tapeto-retinal abiotrophy]. Katsnel'son LA, et al. Vestn Oftalmol, 1977 Nov-Dec. PMID 601959
    3. NEK4 kinase regulates EMT to promote lung cancer metastasis. Ding NH, et al. J Cell Mol Med, 2018 Dec. PMID 30247800, Free PMC Article
    4. Inhibition of never in mitosis A (NIMA)-related kinase-4 reduces survivin expression and sensitizes cancer cells to TRAIL-induced cell death. Park SJ, et al. Oncotarget, 2016 Oct 4. PMID 27602754, Free PMC Article
    5. Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling. Ahmad F, et al. Biochim Biophys Acta Mol Basis Dis, 2020 Mar 1. PMID 31743747, Free PMC Article

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.
      Title: Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.
    2. NRK-2 deficiency promotes post-MI scar expansion, rapid LV chamber dilatation, cardiac dysfunction and fibrosis possibly due to increased p38alpha activation.
      Title: Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling.
    3. this study demonstrates NEK4 as a novel kinase involved in regulation of Epithelial-to-mesenchymal transition.
      Title: NEK4 kinase regulates EMT to promote lung cancer metastasis.
    4. High NEK4 expression is associated with lung cancer and colorectal cancer.
      Title: Inhibition of never in mitosis A (NIMA)-related kinase-4 reduces survivin expression and sensitizes cancer cells to TRAIL-induced cell death.
    5. Nek4 as a novel regulator of replicative senescence and the response to double-stranded DNA damage.
      Title: Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts.
    6. Nek4 interaction with both RPGRIP1 and the RPGRIP1L is involved in cilium assembly.
      Title: The ciliopathy-associated protein homologs RPGRIP1 and RPGRIP1L are linked to cilium integrity through interaction with Nek4 serine/threonine kinase.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
    8. Data show that after Taxol treatment, Nek4 promoted microtubule outgrowth, whereas Nek4 deficiency impaired G(2)-M arrest and decreased formation of mitotic-like asters.
      Title: Nek4 status differentially alters sensitivity to distinct microtubule poisons.
    9. Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.
    Submit: New GeneRIF Correction

    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
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog
    Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
    EBI GWAS Catalog
    Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.
    EBI GWAS Catalog
    Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC33171

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables AMP-activated protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables Rho-dependent protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables eukaryotic translation initiation factor 2alpha kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS121 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AT120 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXS139 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2BS14 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2BS36 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S10 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S28 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S57 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T11 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T3 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T45 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4S1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables manganese ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables ribosomal protein S6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA damage response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA damage response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic cell cycle 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 protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of cellular senescence IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in ciliary basal body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in ciliary plasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in ciliary rootlet IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in ciliary transition zone IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein kinase Nek4
    Names
    NIMA (never in mitosis gene a)-related kinase 4
    never in mitosis A-related kinase 4
    nimA-related protein kinase 4
    serine/threonine kinase 2
    serine/threonine protein kinase-2
    serine/threonine-protein kinase NRK2
    NP_001180462.1
    NP_001335341.1
    NP_001335342.1
    NP_001335343.1
    NP_003148.2
    XP_011532341.1
    XP_011532342.1
    XP_016862574.1
    XP_016862575.1
    XP_047304728.1
    XP_047304730.1
    XP_054203612.1
    XP_054203613.1
    XP_054203614.1
    XP_054203615.1
    XP_054203616.1
    XP_054203617.1

    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_053026.1 RefSeqGene

      Range
      5010..67506
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001193533.3 → NP_001180462.1  serine/threonine-protein kinase Nek4 isoform 2

      See identical proteins and their annotated locations for NP_001180462.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate, in-frame, 5' coding region segment, compared to variant 1. The resulting protein (isoform 2) has a shorter N-terminus when it is compared to isoform 1.
      Source sequence(s)
      AC104446, AK294165, DB073127, L20321
      Consensus CDS
      CCDS54593.1
      UniProtKB/TrEMBL
      E7EX48
      Related
      ENSP00000437703.1, ENST00000535191.5
      Conserved Domains (2) summary
      smart00220
      Location:31 → 172
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:5 → 172
      PKc_like; Protein Kinases, catalytic domain

    2. NM_001348412.2 → NP_001335341.1  serine/threonine-protein kinase Nek4 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC006254, AC104446
      UniProtKB/TrEMBL
      A0A059V7J1
      Conserved Domains (1) summary
      cd08223
      Location:5 → 261
      STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

    3. NM_001348413.2 → NP_001335342.1  serine/threonine-protein kinase Nek4 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon and differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (4) lacks an alternate internal segment and has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC006254
      Consensus CDS
      CCDS87089.1
      UniProtKB/TrEMBL
      A0A059V7J1
      Related
      ENSP00000373227.4, ENST00000383721.8
      Conserved Domains (1) summary
      cd08223
      Location:5 → 261
      STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

    4. NM_001348414.2 → NP_001335343.1  serine/threonine-protein kinase Nek4 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AC006254, AC104446
      UniProtKB/TrEMBL
      E7EX48
      Conserved Domains (1) summary
      cl21453
      Location:1 → 179
      PKc_like; Protein Kinases, catalytic domain

    5. NM_003157.6 → NP_003148.2  serine/threonine-protein kinase Nek4 isoform 1

      See identical proteins and their annotated locations for NP_003148.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC104446, BC015515, DB073127, L20321
      Consensus CDS
      CCDS2863.1
      UniProtKB/Swiss-Prot
      A5YM70, B2R633, B7Z200, P51957, Q6P576
      UniProtKB/TrEMBL
      A0A059V7J1
      Related
      ENSP00000233027.5, ENST00000233027.10
      Conserved Domains (2) summary
      smart00220
      Location:6 → 261
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08223
      Location:5 → 261
      STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      52708444..52770940 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047448772.1 → XP_047304728.1  serine/threonine-protein kinase Nek4 isoform X4

      UniProtKB/TrEMBL
      A0A059V7J1

    2. XM_011534039.4 → XP_011532341.1  serine/threonine-protein kinase Nek4 isoform X2

      UniProtKB/TrEMBL
      A0A059V7J1
      Related
      ENSP00000419666.1, ENST00000461689.5
      Conserved Domains (2) summary
      smart00220
      Location:6 → 261
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08223
      Location:5 → 261
      STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

    3. XM_017007086.2 → XP_016862575.1  serine/threonine-protein kinase Nek4 isoform X3

      UniProtKB/TrEMBL
      A0A059V7J1

    4. XM_017007085.2 → XP_016862574.1  serine/threonine-protein kinase Nek4 isoform X1

      UniProtKB/TrEMBL
      A0A059V7J1

    5. XM_047448774.1 → XP_047304730.1  serine/threonine-protein kinase Nek4 isoform X6

    6. XM_011534040.4 → XP_011532342.1  serine/threonine-protein kinase Nek4 isoform X5

      UniProtKB/TrEMBL
      E7EX48
      Conserved Domains (2) summary
      smart00220
      Location:6 → 261
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd08223
      Location:5 → 261
      STKc_Nek4; Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      52741355..52803847 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054347640.1 → XP_054203615.1  serine/threonine-protein kinase Nek4 isoform X4

      UniProtKB/TrEMBL
      A0A059V7J1

    2. XM_054347638.1 → XP_054203613.1  serine/threonine-protein kinase Nek4 isoform X2

      UniProtKB/TrEMBL
      A0A059V7J1

    3. XM_054347637.1 → XP_054203612.1  serine/threonine-protein kinase Nek4 isoform X1

      UniProtKB/TrEMBL
      A0A059V7J1

    4. XM_054347639.1 → XP_054203614.1  serine/threonine-protein kinase Nek4 isoform X3

      UniProtKB/TrEMBL
      A0A059V7J1

    5. XM_054347642.1 → XP_054203617.1  serine/threonine-protein kinase Nek4 isoform X6

    6. XM_054347641.1 → XP_054203616.1  serine/threonine-protein kinase Nek4 isoform X5

      UniProtKB/TrEMBL
      E7EX48
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51957.2 GenPept UniProtKB/Swiss-Prot:P51957

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