VRK2
protein-codingVRK serine/threonine kinase 2
Gene summary
This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The encoded protein acts as an effector of signaling pathways that regulate apoptosis and tumor cell growth. Variants in this gene have been associated with schizophrenia. Alternative splicing results in multiple transcript variants that differ in their subcellular localization and biological activity. [provided by RefSeq, Jan 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~252.3 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 VRK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006296.7. 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 | 3 | 2 | 5 | |||
| missense | 104 | 6 | 110 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 114 | 8 | 0 | 122 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006287.2 | 12 | MANE Select | |
| Ensembl | ENSP00000342381.4 | 12 | MANE Select | |
| RefSeq | NP_001123952.1 | 12 | Standard | |
| RefSeq | NP_001123953.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Clearance of Nuclear Envelope Membranes from Chromatin
- Nuclear Envelope Breakdown
- Mitotic Prophase
- Initiation of Nuclear Envelope Reformation
- Nuclear Envelope Reassembly
Biological Process
- protein phosphorylation
- viral process
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
- cellular response to oxidative stress
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- protein kinase binding
- protein domain specific binding
Cellular Component
- nucleus
- cytoplasm
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000435505
- Coding exons
- 12
- Length
- 252270
- Individuals with no LoFs
- 125647
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 100
- Defined
- 125747
- p
- 0.000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.949 | 300 | 257 | 1.17 | 0.0000122 | 3329 |
| Missense (PolyPhen) | 97 | 89.337 | 1.0858 | 1167 | ||
| Synonymous | 0.0845 | 89 | 90.0 | 0.989 | 0.00000449 | 901 |
| Loss of Function | 1.39 | 21 | 29.1 | 0.721 | 0.00000141 | 377 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00034 | 0.00032 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00053 | 0.00053 | rare |
| South Asian | 0.00044 | 0.00042 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant.;
Recessive Scores
- pRec
- 0.0962
Intolerance Scores
- LoFtool
- 0.999
- RVIS EVS
- 0.07
- RVIS percentile EVS
- 58.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.951
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |