VRK1

Chr 14

VRK serine/threonine kinase 1

Also known as: HMNR10, PCH1, PCH1A

NCBI Gene: 7443 ENSG00000100749 UniProt: Q99986

The protein is a nuclear serine/threonine kinase that phosphorylates p53, histones, and transcription factors including ATF2 and c-JUN, thereby regulating cell proliferation and transcriptional activity. Autosomal recessive mutations cause pontocerebellar hypoplasia type 1A and distal hereditary motor neuronopathy type 10. The pathogenic mechanism appears to involve dominant-negative effects disrupting normal kinase function.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human tissues and has increased expression in actively dividing cells, such as those in testis, thymus, fetal liver, and carcinomas. Its protein localizes to the nucleus and has been shown to promote the stability and nuclear accumulation of a transcriptionally active p53 molecule and, in vitro, to phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This gene, therefore, may regulate cell proliferation. This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and c-JUN. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPontocerebellar hypoplasia 1A

UniProtNeuronopathy, distal hereditary motor, autosomal recessive 10

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.63

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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