VRK1

Chr 14AR

VRK serine/threonine kinase 1

Also known as: HMNR10, PCH1, PCH1A

NCBI Gene: 7443ENSG00000100749UniProt: Q99986OMIM: 602168

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.632 OMIM phenotypes
Clinical Summary— VRK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 125 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongVRK1-related pontocerebellar hypoplasiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6550th %ile
GOF
0.5562th %ile
LOF
0.3452th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic39
VUS125
Likely Benign177
Benign13
Conflicting3
35
Pathogenic
39
Likely Pathogenic
125
VUS
177
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
0
10
0
35
Likely Pathogenic
34
3
2
0
39
VUS
2
102
16
5
125
Likely Benign
0
2
85
90
177
Benign
0
0
13
0
13
Conflicting
—3
Total6110712695392

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VRK1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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