VRK1

Chr 14AR

VRK serine/threonine kinase 1

Also known as: HMNR10, PCH1, PCH1A

NCBI Gene: 7443ENSG00000100749UniProt: Q99986

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]

Primary Disease Associations & Inheritance

Neuronopathy, distal hereditary motor, autosomal recessive 10MIM #620542
AR
Pontocerebellar hypoplasia type 1AMIM #607596
AR
0
Active trials
0
Pathogenic / LP
0
ClinVar variants
24
Pubs (1 yr)
1.2
Missense Z
0.63
LOEUF
Clinical Summary— VRK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.002
Z-score 2.94
OE 0.36 (0.22–0.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.17Z-score
OE missense 0.78 (0.68–0.88)
167 obs / 215.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.22–0.63)
0≤0.351.4
Missense OE0.78 (0.68–0.88)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 9 / 24.8Missense obs/exp: 167 / 215.2Syn Z: 0.57
DN
DN
0.6550th %ile
GOF
0.5562th %ile
LOF
0.3452th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

VRK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

VRK1-related pontocerebellar hypoplasia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients