VRK1 (Vaccinia Related Kinase 1)
A serine/threonine kinase involved in cell cycle regulation, DNA damage response, and neurodevelopment; mutations cause distal hereditary motor neuropathy and pontocerebellar hypoplasia.
Gene Information Card
| Symbol | VRK1 |
|---|---|
| Full Name | Vaccinia Related Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 7443 ncbi.nlm.nih.gov/gene/7443 |
| Ensembl ID | ENSG00000100726 |
| UniProt ID | Q99986 |
| OMIM ID | 602168 |
| HGNC ID | 12718 |
| Aliases | VRK1, vaccinia related kinase 1 |
Description
VRK1 encodes a serine/threonine protein kinase that belongs to the vaccinia-related kinase family. It plays essential roles in cell cycle progression, chromatin condensation, DNA damage repair, and nuclear envelope dynamics. VRK1 phosphorylates key substrates such as p53, histone H3, and barrier-to-autointegration factor (BAF). Mutations in VRK1 are associated with autosomal recessive distal hereditary motor neuropathy (dHMN) and pontocerebellar hypoplasia type 1 (PCH1).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Distal hereditary motor neuropathy (dHMN) | Loss-of-function mutations impair kinase activity, leading to motor neuron degeneration. | ClinVar, OMIM |
| Pontocerebellar hypoplasia type 1 (PCH1) | Biallelic VRK1 mutations disrupt neurodevelopment and cause cerebellar atrophy. | ClinVar, OMIM |
| Microcephaly | VRK1 deficiency affects cell cycle and DNA repair, contributing to reduced brain size. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Brain | 8.7 | Medium |
| Lymph node | 6.5 | Medium |
| Liver | 4.2 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| HEK293 | 11.4 | Moderate expression |
| SH-SY5Y | 9.8 | Neuronal cell line |
| K562 | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1079G>A (p.Arg360Gln) | Missense | Rare | Loss of kinase activity; associated with dHMN |
| c.1192C>T (p.Arg398*) | Nonsense | Rare | Premature truncation; loss of function; PCH1 |
| c.658C>T (p.Arg220Cys) | Missense | Rare | Impaired substrate binding; dHMN |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein production; PCH1 |
Mutation functional classification
Loss of Function (LOF)
Most VRK1 mutations are loss-of-function, reducing or abolishing kinase activity, leading to impaired cell cycle and DNA repair.
Gain of Function (GOF)
No gain-of-function mutations reported in VRK1.
Dominant Negative (DN)
No dominant-negative mutations reported; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004674 (protein serine/threonine kinase activity) | • GO:0005524 (ATP binding) |
| • GO:0006468 (protein phosphorylation) | • GO:0007049 (cell cycle) |
| • GO:0006974 (DNA damage response) | • GO:0005634 (nucleus) |
| • GO:0016301 (kinase activity) |
Pathways
• Cell cycle (Reactome: R-HSA-1640170)
• DNA damage response (p53 pathway)
• Chromatin condensation (histone H3 phosphorylation)
Protein Summary
VRK1 is a 396-amino acid serine/threonine kinase localized predominantly in the nucleus. It phosphorylates histone H3 at Thr3 and Ser10, p53 at Thr18, and BAF at Ser4, regulating chromatin structure, cell cycle progression, and DNA repair. VRK1 is widely expressed, with highest levels in testis and brain. Loss-of-function mutations cause autosomal recessive neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VRK1 Knockout HAP1 Cell Line | EDC07875 | Human | 7443 | Details Get a Quote |
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