WNK2

Chr 9

WNK lysine deficient protein kinase 2

Also known as: NY-CO-43, P/OKcl.13, PRKWNK2, SDCCAG43

WNK2 encodes a serine/threonine kinase that regulates electrolyte homeostasis through phosphorylation of ion cotransporters and modulates cell signaling pathways including ERK/MAPK. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy or early childhood. The gene is highly constrained against loss-of-function variants, indicating critical importance for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.21
Clinical SummaryWNK2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 7.31
OE 0.12 (0.070.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.58Z-score
OE missense 0.80 (0.760.84)
1024 obs / 1284.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.070.21)
00.351.4
Missense OE0.80 (0.760.84)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 10 / 80.9Missense obs/exp: 1024 / 1284.4Syn Z: -1.24
DN
0.3296th %ile
GOF
0.4184th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

WNK2 · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC