VRK3
protein-codingVRK serine/threonine kinase 3
Gene summary
This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. In both human and mouse, this gene has substitutions at several residues within the ATP binding motifs that in other kinases have been shown to be required for catalysis. In vitro assays indicate the protein lacks phosphorylation activity. The protein, however, likely retains its substrate binding capability. This gene is widely expressed in human tissues and its protein localizes to the nucleus. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VRK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016440.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 54 | 4 | 58 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 60 | 4 | 0 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057524.3 | 12 | MANE Select | |
| Ensembl | ENSP00000324636.2 | 12 | MANE Select | |
| RefSeq | NP_001020949.1 | 11 | Standard | |
| RefSeq | NP_001295349.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toll Like Receptor 7/8 (TLR7/8) Cascade
- Interleukin-17 signaling
- Signal Transduction
- Signaling by Interleukins
- Cytokine Signaling in Immune system
Biological Process
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
- positive regulation of phosphoprotein phosphatase activity
- negative regulation of ERK1 and ERK2 cascade
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- protein phosphatase binding
Cellular Component
- nucleus
- nucleolus
- cytoplasm
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000599538
- Coding exons
- 12
- Length
- 49480
- Individuals with no LoFs
- 125645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 102
- Defined
- 125747
- p
- 0.000406
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.572 | 242 | 268 | 0.902 | 0.0000149 | 3082 |
| Missense (PolyPhen) | 92 | 107.42 | 0.85642 | 1211 | ||
| Synonymous | -0.243 | 112 | 109 | 1.03 | 0.00000630 | 915 |
| Loss of Function | 1.26 | 20 | 27.1 | 0.739 | 0.00000141 | 297 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00040 | 0.00040 | rare |
| Ashkenazi Jewish | 0.0025 | 0.0025 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00042 | 0.00042 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus. {ECO:0000250, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289}.;
Recessive Scores
- pRec
- 0.0818
Intolerance Scores
- LoFtool
- 0.926
- RVIS EVS
- 0.89
- RVIS percentile EVS
- 89.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |