NEK1 — NIMA Related Kinase 1

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gene976 wordssynced 2026-04-02

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">NEK1 — NIMA Related Kinase 1</th>
</tr>
<tr> [@upadhya2000]
<td class="label">Symbol</td> [@white2007]
<td><strong>NEK1</strong></td> [@fang2015]
</tr> [@rifai2025]
<tr> [@sagu2024]
<td class="label">Full Name</td> [@helal2025]
<td>NIMA Related Kinase 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>4q33</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/4750" target="_blank">4750</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137601" target="_blank">ENSG00000137601</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/604588" target="_blank">604588</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q96PY6" target="_blank">Q96PY6</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[ALS](/diseases/als)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Motor cortex, Spinal cord, Widespread</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">Loss-of-function variants<br>p.Arg261His<br>Splice-site mutations</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-la

...

Brain Atlas Resources

[Allen Human Brain Atlas search: NEK1](https://human.brain-map.org/search?searchText=NEK1)
[Allen Mouse Brain Atlas search: NEK1](https://mouse.brain-map.org/search/index.html?query=NEK1)
[Allen Brain Map portal search: NEK1](https://portal.brain-map.org/search?query=NEK1)
[BrainSpan developmental transcriptome search: NEK1](https://www.brainspan.org/search/index.html?search=NEK1)

Introduction

Nek1 — Nima Related Kinase 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Mermaid diagram (expand to render)

NEK1 (NIMA Related Kinase 1, also known as never in mitosis A-related kinase 1) is a serine/threonine kinase gene located on chromosome 4q33 that participates in DNA damage response, ciliogenesis, and cell cycle regulation. A landmark 2016 genome-wide association study identified NEK1 loss-of-function (LOF) variants as a significant genetic risk factor for [amyotrophic lateral sclerosis (ALS)](/diseases/als), with enrichment of rare damaging variants in ALS patients compared to controls ([Kenna et al., 2016](https://doi.org/10.1038/ng.3626)). NEK1 is catalogued as NCBI Gene ID [4750](https://www.ncbi.nlm.nih.gov/gene/4750) and OMIM [604588](https://omim.org/entry/604588).

Function

NEK1 is a multifunctional kinase with roles spanning several critical cellular processes. Unlike most NIMA-related kinases that primarily regulate mitosis, NEK1 has diverged to regulate non-mitotic functions particularly important in post-mitotic [neurons](/entities/neurons).

DNA Damage Response

NEK1 is essential for the ionizing radiation-induced DNA damage response (DDR), where it primes the ATR kinase and phosphorylates Rad54, a key homologous recombination repair factor ([Chen et al., 2011](https://doi.org/10.1038/ncb2382)). NEK1 loss-of-function leads to impaired DDR, resulting in accumulation of DNA damage in motor neurons—a cell type highly vulnerable to genomic instability due to high metabolic demands and long axonal processes ([Higelin et al., 2018](https://doi.org/10.1186/s13287-018-0815-7)).

Ciliogenesis and Primary Cilium

NEK1 localizes to the basal body region and regulates primary cilium assembly and disassembly ([Shalom et al., 2008](https://doi.org/10.1016/j.febslet.2008.01.029)). Mice lacking Nek1 develop polycystic kidney disease (PKD), linking ciliary dysfunction to renal pathology ([Upadhya et al., 2000](https://doi.org/10.1073/pnas.230469597)). NEK1 coordinates ciliogenesis with cell cycle progression, and its overexpression inhibits cilium formation in epithelial cells ([White & Bhatt, 2007](https://doi.org/10.1186/1471-2121-9-29)).

Cytoskeletal Regulation

NEK1 phosphorylates α-tubulin and regulates microtubule stability. NEK1 variants cause decreased α-tubulin acetylation, which impairs axonal transport—a process critical for motor neuron survival ([Fang et al., 2015](https://doi.org/10.1093/hmg/ddv263)).

Brain Expression

NEK1 is broadly expressed across the nervous system including motor [cortex](/brain-regions/cortex), spinal cord motor neurons, and diverse brain regions. Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=NEK1).

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

NEK1 loss-of-function variants confer significant susceptibility to [ALS](/diseases/als) ([Kenna et al., 2016](https://doi.org/10.1038/ng.3626)). The gene interacts with [C21ORF2](/proteins/c9orf72-protein), VCP, and Cyclin F in a converging ALS pathogenesis network ([Helal et al., 2025](https://doi.org/10.3390/genes16040407)).

Key Mutations

| Mutation | Type | Effect |
|----------|------|--------|
| p.Arg261His | Missense | Causes NEK1-positive cytoplasmic aggregates and increased NEK1 mRNA; associated with [TDP-43](/proteins/tdp-43) pathology ([Rifai et al., 2025](https://doi.org/10.1111/bpa.13287)) |
| LOF splice variants | Splice-site | Loss of functional protein, impaired DDR |
| Truncating variants | Frameshift/nonsense | Haploinsufficiency |

Pathogenic Mechanisms

DNA damage accumulation: NEK1 LOF causes impaired DDR, leading to genomic instability in motor neurons ([Higelin et al., 2018](https://doi.org/10.1186/s13287-018-0815-7)).

Mitochondrial dysfunction: NEK1 variants lead to mitochondrial alterations and energy deficits ([Sagu et al., 2024](https://doi.org/10.1093/hmg/ddae122)).

Ciliary dysfunction: NEK1 mutations may impair primary cilium signaling, recently identified as a novel ALS pathogenic mechanism ([Helal et al., 2025](https://doi.org/10.3390/genes16040407)).

Cytoskeletal impairment: Decreased α-tubulin acetylation disrupts microtubule-dependent axonal transport.

Protein aggregation: The p.Arg261His mutation produces NEK1-positive cytoplasmic aggregates, a novel pathological feature ([Rifai et al., 2025](https://doi.org/10.1111/bpa.13287)).

Therapeutic Implications

HDAC6 inhibition: Pharmacological inhibition of HDAC6 restores NEK1-dependent deficits in patient fibroblasts by increasing α-tubulin acetylation, representing an attractive therapeutic strategy ([Fang et al., 2015](https://doi.org/10.1093/hmg/ddv263)).
DNA repair enhancement: Strategies to boost DDR capacity in motor neurons may protect against NEK1-associated neurodegeneration.

External Links

NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/4750](https://www.ncbi.nlm.nih.gov/gene/4750)
Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137601](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137601)
OMIM: [https://omim.org/entry/604588](https://omim.org/entry/604588)
UniProt: [https://www.uniprot.org/uniprot/Q96PY6](https://www.uniprot.org/uniprot/Q96PY6)
Allen Human Brain Atlas: [NEK1 expression](https://human.brain-map.org/microarray/search/show?search_term=NEK1)

Background

The study of Nek1 — Nima Related Kinase 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Kenna KP, et al, NEK1 variants confer susceptibility to amyotrophic lateral sclerosis (2016)](https://doi.org/10.1038/ng.3626)

[Chen Y, et al, NEK1 kinase functions in DNA damage response and checkpoint control (2011)](https://doi.org/10.1038/ncb2382)

[Higelin J, et al, NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons (2018)](https://doi.org/10.1186/s13287-018-0815-7)

[Shalom O, et al, The mammalian Nek1 kinase is involved in primary cilium formation (2008)](https://doi.org/10.1016/j.febslet.2008.01.029)

[Upadhya P, et al, NIMA-related kinases defective in murine models of polycystic kidney diseases (2000)](https://doi.org/10.1073/pnas.230469597)

[White MC, Bhatt KV, The NIMA-family kinase, Nek1 affects the stability of centrosomes and ciliogenesis (2007)](https://doi.org/10.1186/1471-2121-9-29)

[Fang X, et al, NEK1 interacts with C21orf2 in DNA damage response and ALS (2015)](https://doi.org/10.1093/hmg/ddv263)

[Rifai Z, et al, Clinicopathological analysis of NEK1 variants in amyotrophic lateral sclerosis (2025)](https://doi.org/10.1111/bpa.13287)

[Sagu ST, et al, ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, and NEK1 levels (2024)](https://doi.org/10.1093/hmg/ddae122)

[Helal M, et al, The molecular intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS pathogenesis (2025)](https://doi.org/10.3390/genes16040407)

Pathway Diagram

The following diagram shows the key molecular relationships involving NEK1 — NIMA Related Kinase 1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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NEK1 — NIMA Related Kinase 1