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, ... See more...

Aliases for NEK4 Gene

Aliases for NEK4 Gene

  • NIMA Related Kinase 4 2 3 5
  • NIMA (Never In Mitosis Gene A)-Related Kinase 4 2 3
  • Serine/Threonine-Protein Kinase NRK2 3 4
  • Serine/Threonine-Protein Kinase Nek4 3 4
  • Never In Mitosis A-Related Kinase 4 3 4
  • Serine/Threonine Protein Kinase-2 2 3
  • NimA-Related Protein Kinase 4 3 4
  • Serine/Threonine Kinase 2 2 3
  • EC 2.7.11.1 4 52
  • STK2 3 4
  • Serine/Threonine-Protein Kinase Nek4 Variant 2 3
  • Serine/Threonine-Protein Kinase 2 4
  • EC 2.7.11 52
  • Pp12301 3
  • NRK2 3

External Ids for NEK4 Gene

Previous HGNC Symbols for NEK4 Gene

  • STK2

Previous GeneCards Identifiers for NEK4 Gene

  • GC03M051836
  • GC03M051996
  • GC03M052599
  • GC03M052702
  • GC03M052719
  • GC03M052744

Summaries for NEK4 Gene

Entrez Gene Summary for NEK4 Gene

  • 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]

GeneCards Summary for NEK4 Gene

NEK4 (NIMA Related Kinase 4) is a Protein Coding gene. Diseases associated with NEK4 include Ciliopathy. Among its related pathways are Sweet Taste Signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP4K4.

UniProtKB/Swiss-Prot Summary for NEK4 Gene

  • Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage.

Additional gene information for NEK4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NEK4 Gene

Genomics for NEK4 Gene

GeneHancer (GH) Regulatory Elements for NEK4 Gene

Promoters and enhancers for NEK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J052769 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +0.4 380 2.7 ZBTB40 ZNF217 SIN3A NRF1 TCF12 POLR2G GTF2E2 PHF8 ZFX REST NEK4 lnc-ITIH1-3 PBRM1 ITIH3 ITIH4-AS1 ITIH4 ENSG00000243696 SNORD69 GNL3 MUSTN1
GH03J052779 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 500.4 -9.3 -9252 4.8 REST ARNT MEF2B SPI1 SMARCA5 FOXP1 ELF1 EBF1 IKZF1 NR2F1 NEK4 ITIH4 PBRM1 ITIH4-AS1 ENSG00000243696 MUSTN1 STIMATE STIMATE-MUSTN1 WDR82 ITIH3
GH03J053345 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 10.4 -575.9 -575896 3.7 EP300 FOXK2 ZBTB40 ZNF217 ZSCAN5C SIN3A NRF1 MYC TCF12 USF1 DCP1A lnc-PRKCD-3 lnc-TKT-3 NISCH PBRM1 ENSG00000271976 RFT1 PHF7 ENSG00000212608 PRKCD
GH03J052061 Enhancer 1.1 Ensembl ENCODE dbSUPER 12.9 +708.6 708649 3.8 JUND FOS RFX1 ZBTB17 SMARCC1 FOSL2 CEBPB JUN FOSL1 SMARCA5 NEK4 GPR62 LINC00696 DUSP7
GH03J053141 Enhancer 1.1 FANTOM5 ENCODE dbSUPER 11.2 -370.0 -369981 0.4 FOXK2 NRF1 RFX1 ZNF148 SALL2 USF2 USF1 SRF ZNF207 MEF2B GLT8D1 NISCH PRKCD ACTR8 NEK4 RFT1 STIMATE DCP1A ITIH3 PBRM1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NEK4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NEK4

Top Transcription factor binding sites by QIAGEN in the NEK4 gene promoter:
  • aMEF-2
  • CREB
  • deltaCREB
  • Evi-1
  • GR
  • GR-alpha
  • MEF-2A
  • MIF-1
  • Pax-5
  • POU2F1a

Genomic Locations for NEK4 Gene

Genomic Locations for NEK4 Gene
chr3:52,708,444-52,770,949
(GRCh38/hg38)
Size:
62,506 bases
Orientation:
Minus strand
chr3:52,744,796-52,804,965
(GRCh37/hg19)
Size:
60,170 bases
Orientation:
Minus strand

Genomic View for NEK4 Gene

Genes around NEK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NEK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NEK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NEK4 Gene

Proteins for NEK4 Gene

  • Protein details for NEK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51957-NEK4_HUMAN
    Recommended name:
    Serine/threonine-protein kinase Nek4
    Protein Accession:
    P51957
    Secondary Accessions:
    • A5YM70
    • B2R633
    • B7Z200
    • Q6P576

    Protein attributes for NEK4 Gene

    Size:
    841 amino acids
    Molecular mass:
    94597 Da
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Interacts with RPGRIP1 and RPGRIP1L.

    Alternative splice isoforms for NEK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NEK4 Gene

Selected DME Specific Peptides for NEK4 Gene

P51957:
  • ILHRDLK
  • GTPYYMSPE

Post-translational modifications for NEK4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for NEK4 Gene

Gene Families for NEK4 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for NEK4 Gene

Suggested Antigen Peptide Sequences for NEK4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ53862, highly similar to Homo sapiens NIMA (never in mitosis gene a)-related kinase 4 (NEK4), mRNA (B7Z200_HUMAN)
  • Serine/threonine-protein kinase NRK2 (NEK4_HUMAN)
  • NEK4 protein (Q05DF6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P51957

UniProtKB/Swiss-Prot:

NEK4_HUMAN :
  • Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Family:
  • Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
genes like me logo Genes that share domains with NEK4: view

Function for NEK4 Gene

Molecular function for NEK4 Gene

UniProtKB/Swiss-Prot Function:
Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence=. ;.

Enzyme Numbers (IUBMB) for NEK4 Gene

Phenotypes From GWAS Catalog for NEK4 Gene

Gene Ontology (GO) - Molecular Function for NEK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity TAS,ISS --
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with NEK4: view
genes like me logo Genes that share phenotypes with NEK4: view

Animal Model Products

  • Taconic Biosciences Mouse Models for NEK4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NEK4

Clone Products

  • Addgene plasmids for NEK4

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NEK4 Gene

Localization for NEK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NEK4 Gene

Cell projection, cilium. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NEK4 gene
Compartment Confidence
cytosol 5
nucleus 4
cytoskeleton 3
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NEK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA,ISS --
GO:0005829 cytosol IDA --
GO:0005929 cilium IEA --
GO:0035253 ciliary rootlet IEA --
GO:0035869 ciliary transition zone IEA --
genes like me logo Genes that share ontologies with NEK4: view

Pathways & Interactions for NEK4 Gene

PathCards logo

SuperPathways for NEK4 Gene

SuperPathway Contained pathways
1 Sweet Taste Signaling
.37
genes like me logo Genes that share pathways with NEK4: view

Pathways by source for NEK4 Gene

1 Qiagen pathway for NEK4 Gene
  • Sperm Motility

Gene Ontology (GO) - Biological Process for NEK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000278 mitotic cell cycle IMP 22851694
GO:0006468 protein phosphorylation ISS --
GO:0006974 cellular response to DNA damage stimulus IMP 22851694
GO:0007049 cell cycle IEA --
GO:0016310 phosphorylation IEA --
genes like me logo Genes that share ontologies with NEK4: view

No data available for SIGNOR curated interactions for NEK4 Gene

Drugs & Compounds for NEK4 Gene

(3) Drugs for NEK4 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0

(1) Additional Compounds for NEK4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with NEK4: view

Transcripts for NEK4 Gene

mRNA/cDNA for NEK4 Gene

5 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NEK4

Clone Products

  • Addgene plasmids for NEK4

Alternative Splicing Database (ASD) splice patterns (SP) for NEK4 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17a · 17b ^ 18
SP1: - - -
SP2: - - -
SP3:
SP4: -
SP5:
SP6: -

Relevant External Links for NEK4 Gene

GeneLoc Exon Structure for
NEK4

Expression for NEK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NEK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NEK4 Gene

This gene is overexpressed in Adipocyte (25.5), Testis (15.0), Tlymphocyte (12.4), and Peripheral blood mononuclear cells (9.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NEK4 Gene



Protein tissue co-expression partners for NEK4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NEK4

SOURCE GeneReport for Unigene cluster for NEK4 Gene:

Hs.631921

mRNA Expression by UniProt/SwissProt for NEK4 Gene:

P51957-NEK4_HUMAN
Tissue specificity: Highest expression in adult heart, followed by pancreas, skeletal muscle, brain, testis, retina, liver, kidney, lung and placenta. Present in most primary carcinomas.

Evidence on tissue expression from TISSUES for NEK4 Gene

  • Nervous system(4.6)
genes like me logo Genes that share expression patterns with NEK4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NEK4 Gene

Orthologs for NEK4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NEK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NEK4 30
  • 99.35 (n)
cow
(Bos Taurus)
Mammalia NEK4 31 30
  • 86.87 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NEK4 31 30
  • 86.74 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Nek4 17 31 30
  • 82.61 (n)
rat
(Rattus norvegicus)
Mammalia Nek4 30
  • 81.08 (n)
oppossum
(Monodelphis domestica)
Mammalia NEK4 31
  • 65 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NEK4 31
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves NEK4 31 30
  • 65.24 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NEK4 31
  • 56 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nek4 30
  • 56.57 (n)
Str.18724 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.18997 30
zebrafish
(Danio rerio)
Actinopterygii nek4 31 30
  • 67.59 (n)
OneToOne
-- 30
worm
(Caenorhabditis elegans)
Secernentea Y39G10AR.4 32
  • 42 (a)
ZC581.1 32
  • 32 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 68 (a)
OneToOne
Species where no ortholog for NEK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NEK4 Gene

ENSEMBL:
Gene Tree for NEK4 (if available)
TreeFam:
Gene Tree for NEK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NEK4: view image

Paralogs for NEK4 Gene

genes like me logo Genes that share paralogs with NEK4: view

Variants for NEK4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NEK4 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
730038 Likely Benign: not provided 52,737,634(-) T/C SYNONYMOUS_VARIANT
rs770418305 Likely Pathogenic: Ciliopathy 52,741,486(-) A/AT FRAMESHIFT_VARIANT
VAR_040921 A colorectal adenocarcinoma sample p.Arg777Lys
rs1029871 - p.Pro225Ala
rs2230537 - p.Thr357Ile

Additional dbSNP identifiers (rs#s) for NEK4 Gene

Structural Variations from Database of Genomic Variants (DGV) for NEK4 Gene

Variant ID Type Subtype PubMed ID
esv2762328 CNV loss 21179565
esv3596162 CNV loss 21293372
nsv1010761 CNV gain 25217958
nsv508219 CNV deletion 20534489
nsv508928 CNV insertion 20534489
nsv834698 CNV gain 17160897

Variation tolerance for NEK4 Gene

Residual Variation Intolerance Score: 33.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.57; 88.96% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NEK4 Gene

Human Gene Mutation Database (HGMD)
NEK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NEK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NEK4 Gene

Disorders for NEK4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for NEK4 Gene - From: GeneCards

Disorder Aliases PubMed IDs
ciliopathy
- elite association - COSMIC cancer census association via MalaCards
Search NEK4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NEK4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NEK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NEK4 Gene

Publications for NEK4 Gene

  1. Two novel human serine/threonine kinases with homologies to the cell cycle regulating Xenopus MO15, and NIMA kinases: cloning and characterization of their expression pattern. (PMID: 8208544) Levedakou EN … Lewis TB (Oncogene 1994) 2 3 4 54
  2. Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts. (PMID: 22851694) Nguyen CL … Hahn WC (Molecular and cellular biology 2012) 3 4 54
  3. The ciliopathy-associated protein homologs RPGRIP1 and RPGRIP1L are linked to cilium integrity through interaction with Nek4 serine/threonine kinase. (PMID: 21685204) Coene KL … Roepman R (Human molecular genetics 2011) 3 4 54
  4. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PMID: 20800603) Flachsbart F … Nebel A (Mutation research 2010) 3 41 54
  5. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 41 54

Products for NEK4 Gene

Sources for NEK4 Gene