VRK3 (Vaccinia Related Kinase 3)
A pseudokinase involved in cell cycle regulation and neurological disorders
Gene Information Card
| Symbol | VRK3 |
|---|---|
| Full Name | Vaccinia Related Kinase 3 |
| Gene Type | Protein coding (pseudokinase) |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 51231 ncbi.nlm.nih.gov/gene/51231 |
| Ensembl ID | ENSG00000105048 |
| UniProt ID | Q8IV63 |
| OMIM ID | 618224 |
| HGNC ID | 12718 |
| Aliases | VRK-3, FLJ11127 |
Description
VRK3 encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. Unlike other VRK family members, VRK3 lacks catalytic activity due to critical substitutions in the ATP-binding site, functioning as a pseudokinase. It plays a role in cell cycle regulation, particularly in the G1/S transition, and interacts with proteins such as BAF (barrier-to-autointegration factor). VRK3 is widely expressed and has been implicated in neurological conditions and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability | VRK3 mutations may disrupt neuronal development and synaptic function | ClinVar, OMIM |
| Autism spectrum disorder | Rare variants in VRK3 associated with ASD risk | ClinVar |
| Cancer (general) | Altered VRK3 expression may affect cell cycle control | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.2 | Medium |
| Lung | 8.9 | Medium |
| Liver | 6.1 | Low |
| Heart | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | Embryonic kidney |
| SH-SY5Y | 14.2 | Neuroblastoma |
| HeLa | 11.8 | Cervical cancer |
| A549 | 9.5 | Lung cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497C>T (p.Thr166Ile) | Missense | Rare | Likely pathogenic in intellectual disability |
| c.104G>A (p.Arg35Gln) | Missense | Rare | Uncertain significance |
| c.1234delG | Frameshift | Very rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.1234delG) predicted to cause loss of VRK3 pseudokinase function.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not established for VRK3.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity (GO:0004672) | • ATP binding (GO:0005524) |
| • cell cycle (GO:0007049) | • nucleus (GO:0005634) |
| • kinase activity (GO:0016301) |
Pathways
• Cell cycle (Reactome: R-HSA-1640170)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
Protein Summary
VRK3 is a 474-amino acid pseudokinase that lacks catalytic activity due to substitutions in the ATP-binding motif (e.g., Lys179Glu). It localizes to the nucleus and interacts with BAF, influencing cell cycle progression. VRK3 is expressed in multiple tissues, with highest levels in brain and testis. Mutations in VRK3 are associated with neurodevelopmental disorders, and altered expression is observed in some cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VRK3 Knockout HEK293 Cell Line | EDJ-KQ10276 | Human | 51231 | Details Get a Quote |
| VRK3 Knockout A-549 Cell Line | EDJ-KQ38822 | Human | 51231 | Details Get a Quote |
| VRK3 Knockout HCT 116 Cell Line | EDJ-KQ38823 | Human | 51231 | Details Get a Quote |
| VRK3 Knockout HeLa Cell Line | EDJ-KQ38824 | Human | 51231 | Details Get a Quote |
