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WNK1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

WNK1 gene

The WNK1 gene provides instructions for creating proteins that regulate blood pressure, electrolyte balance, and pain sensation throughout the body.

Normal Function

The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. These isoforms are essential for several bodily functions, including blood pressure regulation and pain sensation.

  • L-WNK1 protein: A full-length version found in cells throughout the body. It increases sodium reabsorption and decreases potassium secretion.
  • KS-WNK1 protein: A kidney-specific version that has the opposite effect of L-WNK1, helping to maintain the correct balance of sodium and potassium for healthy blood pressure.
  • WNK1/HSN2 protein: Found in the nervous system, including sensory neurons that transmit pain, temperature, and touch. It regulates chloride ion channels, which are important for controlling the excitation of neurons.

The L-WNK1 and KS-WNK1 proteins act as kinases, enzymes that modify the activity of other proteins by adding a phosphate group. They regulate cell membrane channels that control the transport of sodium and potassium in the kidneys.

Health Conditions Related to Genetic Changes

Hereditary sensory and autonomic neuropathy type II

Mutations in the WNK1 gene are responsible for HSAN2A, a condition where individuals lose the ability to feel pain or sense hot and cold. These mutations lead to an abnormally shortened, nonfunctional WNK1/HSN2 protein, resulting in a reduction of sensory neurons.

Pseudohypoaldosteronism type 2

Mutations that delete large numbers of DNA building blocks from the WNK1 gene can cause pseudohypoaldosteronism type 2 (PHA2). This condition is characterized by:

  • High blood pressure (hypertension)
  • High levels of potassium in the blood (hyperkalemia)

These mutations increase the activity of the WNK1 gene, leading to an excess of L-WNK1 protein, which abnormally increases sodium reabsorption and blocks potassium secretion.

Other disorders

Normal variations in the WNK1 gene have been associated with an increased risk of high blood pressure in the general population, likely influenced by a combination of genetic and environmental factors.

Frequently Asked Questions

Individuals presenting with unexplained high blood pressure and hyperkalemia, or those with a family history of early‑onset hypertension and sensory neuropathy, should be evaluated for WNK1 mutations. Testing is performed via blood or saliva samples and analyzed by targeted sequencing or multiplex ligation‑dependent probe amplification to detect deletions or point mutations.
The deletion increases the activity of the L‑WNK1 kinase, which enhances sodium reabsorption and reduces potassium excretion in the kidneys. This results in hypertension and hyperkalemia. Treatment typically includes thiazide or loop diuretics to promote potassium loss, potassium‑binding resins, and sometimes mineralocorticoid receptor antagonists to counteract the hormonal imbalance.
Yes. Reducing dietary sodium, limiting potassium‑rich foods, and maintaining a healthy weight can lower blood pressure. Regular monitoring of serum potassium and blood pressure at home or in clinic is essential to adjust medications and dietary plans.
Patients with WNK1/HSN2 mutations often report numbness or a complete loss of pain perception, especially in the extremities. They may also describe an inability to sense hot or cold temperatures, leading to unnoticed injuries such as burns or fractures. Early evaluation by a neurologist and sensory testing can confirm the diagnosis.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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