WNK2
protein-codingWNK lysine deficient protein kinase 2, the group of WNK lysine deficient protein kinases
Gene summary
The protein encoded by this gene is a cytoplasmic serine-threonine kinase that belongs to the protein kinase superfamily. The protein plays an important role in the regulation of electrolyte homeostasis, cell signaling survival, and proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
- SDCCAG43
- PRKWNK2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~136.5 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 WNK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006648.4. 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 | 6 | 1303 | 1309 | |||
| missense | 2177 | 100 | 1 | 2278 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 4 | |||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 1 | 2191 | 1403 | 1 | 3596 |
Highest pathogenic variant AF is 0.000004466724
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006639.3 | 29 | MANE Select | |
| Ensembl | ENSP00000411181.4 | 29 | MANE Select | |
| RefSeq | NP_001269323.1 | 30 | Standard | |
| Ensembl | ENSP00000297954.4 | 30 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- protein phosphorylation
- negative regulation of cell population proliferation
- negative regulation of sodium ion transport
- positive regulation of ion transmembrane transporter activity
- intracellular signal transduction
Molecular Function
- protein serine/threonine kinase activity
- ATP binding
- chloride channel inhibitor activity
- potassium channel inhibitor activity
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297954
- Coding exons
- 30
- Length
- 135657
- Individuals with no LoFs
- 125594
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125606
- p
- 0.0000478
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.58 | 1024 | 1.28e+3 | 0.797 | 0.0000858 | 14370 |
| Missense (PolyPhen) | 32 | 39.979 | 0.80043 | 402 | ||
| Synonymous | -1.24 | 657 | 618 | 1.06 | 0.0000479 | 5047 |
| Loss of Function | 7.31 | 10 | 80.9 | 0.124 | 0.00000413 | 931 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000039 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1. WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity. {ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}.;
Recessive Scores
- pRec
- 0.122
Essentials
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.583
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |