NEK1 (NIMA Related Kinase 1): ALS, PKD, and Ciliary Signaling
A comprehensive biomedical overview of NEK1, its genomic architecture, expression, disease associations, and functional roles.
Gene Information Card
| Symbol | NEK1 |
|---|---|
| Full Name | NIMA related kinase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 4q33 |
| NCBI Gene ID | 4750 ncbi.nlm.nih.gov/gene/4750 |
| Ensembl ID | ENSG00000109458 |
| UniProt ID | Q96PY6 |
| OMIM ID | 604798 |
| HGNC ID | 7744 |
| Aliases | NIMA (never in mitosis gene a)-related kinase 1; KIAA1901; NYD-SP27 |
Description
NEK1 encodes a serine/threonine kinase belonging to the NIMA (never in mitosis gene A) family. It plays critical roles in cell cycle regulation, DNA damage response, ciliary function, and mitochondrial homeostasis. Mutations in NEK1 are associated with amyotrophic lateral sclerosis (ALS) and polycystic kidney disease (PKD). The protein localizes to centrosomes, cilia, and mitochondria, and is involved in phosphorylation of multiple substrates.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Loss-of-function mutations (e.g., frameshift, splice-site) impair DNA damage repair and mitochondrial function, leading to motor neuron degeneration. | ClinVar, multiple case-control studies (e.g., Kenna et al., 2016) |
| Polycystic Kidney Disease (PKD) | Mutations disrupt ciliary signaling and cell cycle control, causing cyst formation in renal tubules. | OMIM, mouse models (e.g., NEK1-deficient mice) |
| Short-rib thoracic dysplasia (SRTD6) | Biallelic mutations cause ciliary dysfunction leading to skeletal and renal anomalies. | OMIM, case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Kidney | 8.7 | Low |
| Brain (cerebellum) | 6.3 | Low |
| Liver | 4.1 | Low |
| Lung | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.5 | Embryonic kidney cells; high expression |
| HeLa | 8.9 | Cervical cancer cells; moderate |
| A549 | 6.2 | Lung carcinoma; low-moderate |
| MCF7 | 5.4 | Breast cancer; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg261His | Missense | Rare (<0.1%) | Likely benign; found in ALS cases but also controls |
| p.Leu539Phe | Missense | Rare (<0.1%) | Uncertain significance; potential effect on kinase activity |
| c.1105C>T (p.Arg369*) | Nonsense | Very rare | Loss-of-function; associated with ALS |
| c.2146+1G>A | Splice-site | Very rare | Loss-of-function; associated with ALS |
Mutation functional classification
Loss of Function (LOF)
Most ALS-associated NEK1 mutations are loss-of-function (LOF), leading to haploinsufficiency. LOF impairs DNA damage repair and mitochondrial function, increasing neuronal vulnerability.
Gain of Function (GOF)
No clear gain-of-function mutations reported. Some missense variants may alter kinase activity but evidence is limited.
Dominant Negative (DN)
Not established for NEK1. LOF is the primary mechanism; dominant-negative effects are not supported by current data.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • centrosome | • cilium |
| • mitochondrion | • DNA damage response |
| • cell cycle | • phosphorylation |
Pathways
• DNA damage response (ATM/ATR signaling)
• Ciliary signaling (Hedgehog pathway)
• Mitochondrial apoptosis pathway
• Cell cycle checkpoint regulation
Protein Summary
NEK1 is a 1258-amino-acid protein with an N-terminal kinase domain and a C-terminal regulatory region. It phosphorylates substrates involved in DNA repair (e.g., Rad54) and ciliary function. NEK1 interacts with NEK8 and other ciliary proteins. Its kinase activity is essential for G2/M checkpoint and ciliary disassembly. Mutations causing loss of function lead to defective DNA repair and mitochondrial dysfunction, contributing to ALS pathology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEK1 Knockout HEK293 Cell Line | EDJ-KQ1954 | Human | 4750 | Details Get a Quote |
| NEK10 Knockout HEK293 Cell Line | EDJ-KQ10694 | Human | 152110 | Details Get a Quote |
| NEK11 Knockout HEK293 Cell Line | EDJ-KQ14410 | Human | 79858 | Details Get a Quote |
| NEK11 Knockout A-549 Cell Line | EDJ-KQ44606 | Human | 79858 | Details Get a Quote |
| NEK11 Knockout HCT 116 Cell Line | EDJ-KQ44607 | Human | 79858 | Details Get a Quote |
| NEK1 Knockout HCT 116 Cell Line | EDJ-KQ20614 | Human | 4750 | Details Get a Quote |
| NEK1 Knockout A-549 Cell Line | EDJ-KQ21906 | Human | 4750 | Details Get a Quote |
| NEK1 Knockout HeLa Cell Line | EDJ-KQ21907 | Human | 4750 | Details Get a Quote |
| NEK10 Knockout A-549 Cell Line | EDJ-KQ39571 | Human | 152110 | Details Get a Quote |
| NEK10 Knockout HCT 116 Cell Line | EDJ-KQ39573 | Human | 152110 | Details Get a Quote |
| NEK10 Knockout HeLa Cell Line | EDJ-KQ39574 | Human | 152110 | Details Get a Quote |
| NEK11 Knockout HeLa Cell Line | EDJ-KQ57245 | Human | 79858 | Details Get a Quote |
