| NEK1 — NIMA Related Kinase 1 | |
|---|---|
| Symbol | NEK1 |
| Full Name | NIMA Related Kinase 1 |
| Chromosome | 4q33 |
| NCBI Gene | 4750 |
| Ensembl | ENSG00000137601 |
| OMIM | 604588 |
| UniProt | Q96PY6 |
| Diseases | ALS |
| Expression | Motor cortex, Spinal cord, Widespread |
| Key Mutations | |
| Loss-of-function variants p.Arg261His Splice-site mutations |
|
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.
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), with enrichment of rare damaging variants in ALS patients compared to controls (Kenna et al., 2016). NEK1 is catalogued as NCBI Gene ID 4750 and OMIM 604588.
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.
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). 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).
NEK1 localizes to the basal body region and regulates primary cilium assembly and disassembly (Shalom et al., 2008). Mice lacking Nek1 develop polycystic kidney disease (PKD), linking ciliary dysfunction to renal pathology (Upadhya et al., 2000). NEK1 coordinates ciliogenesis with cell cycle progression, and its overexpression inhibits cilium formation in epithelial cells (White & Bhatt, 2007).
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).
NEK1 is broadly expressed across the nervous system including motor cortex, spinal cord motor neurons, and diverse brain regions. Expression data is available from the Allen Human Brain Atlas.
NEK1 loss-of-function variants confer significant susceptibility to ALS (Kenna et al., 2016). The gene interacts with C21ORF2, VCP, and Cyclin F in a converging ALS pathogenesis network (Helal et al., 2025).
| Mutation | Type | Effect |
|---|---|---|
| p.Arg261His | Missense | Causes NEK1-positive cytoplasmic aggregates and increased NEK1 mRNA; associated with TDP-43 pathology (Rifai et al., 2025) |
| LOF splice variants | Splice-site | Loss of functional protein, impaired DDR |
| Truncating variants | Frameshift/nonsense | Haploinsufficiency |
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.
Page expanded by NeuroWiki quality review. Last updated: 2026-02-27.