NEK8: NIMA Related Kinase 8
A key regulator of ciliary function and cell cycle progression, implicated in nephronophthisis and related ciliopathies.
Gene Information Card
| Symbol | NEK8 |
|---|---|
| Full Name | NIMA related kinase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 284086 ncbi.nlm.nih.gov/gene/284086 |
| Ensembl ID | ENSG00000160606 |
| UniProt ID | Q86SG6 |
| OMIM ID | 609799 |
| HGNC ID | 13387 |
| Aliases | NPHP9, JCK, NEK12A |
Description
NEK8 (NIMA related kinase 8) encodes a serine/threonine kinase belonging to the NEK family, which is involved in cell cycle regulation and ciliary function. The protein localizes to the proximal region of the primary cilium and is essential for ciliary signaling and maintenance. Mutations in NEK8 cause nephronophthisis type 9 (NPHP9), a renal ciliopathy characterized by cystic kidney disease, and are also associated with other ciliopathy phenotypes including cardiac and skeletal anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nephronophthisis 9 (NPHP9) | Loss-of-function mutations in NEK8 disrupt ciliary localization and function, leading to renal tubular degeneration and cyst formation. | OMIM #609799; ClinVar; PMID: 23349334 |
| Renal-hepatic-pancreatic dysplasia (RHPD) | NEK8 mutations impair ciliary signaling pathways, contributing to syndromic ciliopathy with multiorgan involvement. | OMIM #609799; PMID: 23349334 |
| Ciliopathy-related cardiac defects | NEK8 dysfunction alters Hedgehog and other ciliary signaling, associated with congenital heart defects in some patients. | PMID: 23349334; PMID: 25652405 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 8.2 | Medium |
| Testis | 6.5 | Medium |
| Liver | 4.1 | Low |
| Heart | 3.8 | Low |
| Brain | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.3 | Embryonic kidney cells; high expression |
| HepG2 | 5.6 | Liver cancer cell line; moderate expression |
| K562 | 3.1 | Leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.428C>T (p.Pro143Leu) | Missense | Rare | Loss of kinase activity; disrupts ciliary localization |
| c.1045C>T (p.Arg349*) | Nonsense | Rare | Premature truncation; loss of function |
| c.1645G>A (p.Gly549Arg) | Missense | Rare | Impaired protein stability; reduced ciliary function |
Mutation functional classification
Loss of Function (LOF)
Most NEK8 disease-associated mutations are loss-of-function, leading to reduced kinase activity or protein instability, impairing ciliary function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NEK8.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type NEK8 localization or function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ciliary signaling pathway (Hedgehog
• Wnt)
• Cell cycle regulation (G2/M transition)
Protein Summary
NEK8 is a 692-amino acid serine/threonine kinase with an N-terminal catalytic domain and a C-terminal regulatory region. It localizes to the proximal region of the primary cilium and is required for ciliary assembly and signaling. The protein interacts with other ciliary proteins such as NPHP1 and NPHP4, and its kinase activity is essential for proper cell cycle progression and ciliary function. Loss of NEK8 function leads to ciliary defects and contributes to nephronophthisis and related ciliopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEK8 Knockout HEK293 Cell Line | EDJ-KQ12127 | Human | 284086 | Details Get a Quote |
| NEK8 Knockout A-549 Cell Line | EDJ-KQ40816 | Human | 284086 | Details Get a Quote |
| NEK8 Knockout HCT 116 Cell Line | EDJ-KQ40817 | Human | 284086 | Details Get a Quote |
| NEK8 Knockout HeLa Cell Line | EDJ-KQ40818 | Human | 284086 | Details Get a Quote |
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