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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NEK4
NIMA related kinase 4
Chromosome 3 Β· 3p21.1
NCBI Gene: 6787Ensembl: ENSG00000114904.14HGNC: HGNC:11399UniProt: P51957
40PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA damage responsemitotic cell cyclepositive regulation of DNA-templated transcriptioncytosolneurodegenerative diseaseosteoarthritis, hiposteoarthritis, kneetotal joint arthroplasty
✦AI Summary

NEK4 (NIMA-related kinase 4) is a serine/threonine protein kinase with critical roles in cell cycle regulation, DNA damage response, and neurological function 1. The protein is essential for normal entry into replicative senescence after a limited number of cell divisions, as NEK4 suppression extends cellular lifespan and decreases p21 transcription 1. Mechanistically, NEK4 forms complexes with DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku70, and Ku80, and is required for proper DNA-PKcs recruitment to DNA damage sites, enabling p53 activation and H2AX phosphorylation 1. Beyond cell cycle control, NEK4 has significant neuropsychiatric relevance, with elevated hippocampal expression associated with increased bipolar disorder risk 2. NEK4 overexpression in male mice causes circadian shifts in anxiety-like behaviors and affects synaptic structure and dendritic spine morphology 2. The gene exists as two isoforms with distinct interaction profiles, both involved in DNA damage response, cilia maintenance, and RNA splicing control 3. NEK4 has emerged as a potential therapeutic target for multiple psychiatric disorders including schizophrenia and bipolar disorder 45, and has been identified as a candidate gene in ciliopathies 6.

Sources cited
1
NEK4 is required for replicative senescence, forms DNA-PK complexes, and regulates DNA damage response
PMID: 22851694
2
NEK4 overexpression affects circadian anxiety behaviors and synaptic structure in mice, with elevated expression linked to bipolar disorder risk
PMID: 39448584
3
NEK4 is identified as a shared risk protein for schizophrenia and bipolar disorder through proteome-wide association studies
PMID: 38869147
4
NEK4 identified as genetically supported drug target for schizophrenia and bipolar disorder through Mendelian randomization
PMID: 37418754
5
NEK4 has two isoforms with distinct interaction profiles involved in DNA damage response, cilia maintenance, and RNA splicing
PMID: 25798074
6
NEK4 identified as novel candidate gene in ciliopathies genomic analysis
PMID: 27894351
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.36Weak
osteoarthritis, hipOpen Targets
0.33Weak
osteoarthritis, kneeOpen Targets
0.31Weak
total joint arthroplastyOpen Targets
0.28Weak
ciliopathyOpen Targets
0.26Weak
bipolar disorderOpen Targets
0.16Weak
schizophreniaOpen Targets
0.16Weak
pituitary gland diseaseOpen Targets
0.12Weak
hypertensionOpen Targets
0.09Suggestive
intelligenceOpen Targets
0.08Suggestive
ureterolithiasisOpen Targets
0.08Suggestive
essential hypertensionOpen Targets
0.08Suggestive
Inguinal herniaOpen Targets
0.08Suggestive
Abnormality of the skeletal systemOpen Targets
0.07Suggestive
nephrolithiasisOpen Targets
0.07Suggestive
osteoarthritisOpen Targets
0.06Suggestive
nervous system diseaseOpen Targets
0.06Suggestive
psychiatric disorderOpen Targets
0.06Suggestive
eye diseaseOpen Targets
0.06Suggestive
cataractOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_003157.6(NEK4):c.2017dup (p.Ile673fs)Likely pathogenic
Ciliopathy
β˜†β˜†β˜†β˜†β†’ Residue 673
View on ClinVar β†—
Related Genes
RPGRIP1LProtein interaction90%NRBP2Shared pathway40%WNK2Shared pathway38%NRBP1Shared pathway36%SGK2Shared pathway29%MKNK1Shared pathway29%
Tissue Expression6 tissues
Liver
100%
Brain
97%
Ovary
96%
Bone Marrow
93%
Heart
89%
Lung
53%
Gene Interaction Network
Click a node to explore
NEK4RPGRIP1LNRBP2WNK2NRBP1SGK2MKNK1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P51957
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.16LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.94 [0.77–1.16]
RankingsWhere NEK4 stands among ~20K protein-coding genes
  • #10,214of 20,598
    Most Researched40
  • #5,172of 5,498
    Most Pathogenic Variants1
  • #12,095of 17,882
    Most Constrained (LOEUF)1.16
Genes detectedNEK4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Characterizing the morbid genome of ciliopathies.
PMID: 27894351
Genome Biol Β· 2016
1.00
2
NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice.
PMID: 39448584
Nat Commun Β· 2024
0.90
3
Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.
PMID: 38869147
Schizophr Bull Β· 2024
0.80
4
Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts.
PMID: 22851694
Mol Cell Biol Β· 2012
0.70
5
Mendelian Randomization Using the Druggable Genome Reveals Genetically Supported Drug Targets for Psychiatric Disorders.
PMID: 37418754
Schizophr Bull Β· 2023
0.60