VRK1

The VRK1 gene provides instructions for making a protein called vaccinia-related kinase 1. This protein is active in cells throughout the body.

Vaccinia-related kinase 1 plays a critical role in directing cell growth and division. This protein regulates several transcription factors, which are proteins that control the activity of genes by attaching (binding) to specific regions of DNA. Vaccinia-related kinase 1 has a particularly important role in regulating a transcription factor called p53 (which is produced from the TP53 gene). The p53 protein repairs damaged DNA, regulates cell division, and prevents the formation of cancerous tumors. Vaccinia-related kinase 1 stabilizes and activates the p53 protein and controls the levels of p53 in the nucleus.

Studies suggest that vaccinia-related kinase 1 has several additional functions related to cell division. This protein is involved in the assembly of the nuclear envelope, which is a structure that surrounds the nucleus and acts as a barrier between the nucleus and the rest of the cell. The nuclear envelope protects the DNA contained in the nucleus and regulates the movement of molecules into and out of the nucleus. Vaccinia-related kinase 1 is also thought to play a role in the organization of chromatin. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. Both the assembly of the nuclear envelope and the proper organization of chromatin are necessary for normal cell division.

pontocerebellar hypoplasia - caused by mutations in the VRK1 gene

At least one mutation in the VRK1 gene has been found to cause pontocerebellar hypoplasia type 1 (PCH1). This mutation, which is written as Arg358Ter or R358X, introduces a premature stop signal in the instructions for making vaccinia-related kinase 1. As a result, cells make significantly less of this protein than usual. A shortage of vaccinia-related kinase 1 prevents this protein from interacting with other transcription factors, which likely affects cell growth and division. However, it is unclear how a lack of this protein disrupts normal brain development in people with PCH1. Researchers speculate that vaccinia-related kinase 1 may be involved in the development and maintenance of the nervous system in ways that are not well understood. It appears that mutations in the VRK1 gene are responsible for only a small percentage of all cases of PCH1.