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

Gene ID: 6787, updated on 2-Nov-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
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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: 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. 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)

Genotypes

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 ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS1 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
  
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

  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

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

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

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

  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

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

Gene LinkOut

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