WNK1
Chr 12ARADWNK lysine deficient protein kinase 1
Also known as: HSAN2, HSN2, KDP, PPP1R167, PRKWNK1, PSK, p65
This gene encodes a serine/threonine protein kinase that regulates blood pressure by controlling sodium and chloride ion transport and acts as a molecular crowding sensor mediating cellular volume regulation. Mutations cause pseudohypoaldosteronism type IIC (autosomal dominant) and hereditary sensory and autonomic neuropathy type II (autosomal recessive), affecting renal electrolyte handling and peripheral sensory function respectively. WNK1 is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.126), indicating that complete loss of function is likely incompatible with normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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.
Literature Evidence
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
WNK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools