GENE REFERENCE / HGNC:14540

WNK1

WNK lysine deficient protein kinase 1

protein-coding gene12p13.33Gene information

What does this gene do?

The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. The different WNK1 isoforms are important in several functions in the body, including blood pressure regulation and pain sensation.

One isoform produced from the WNK1 gene is the full-length version, called the L-WNK1 protein, which is found in cells throughout the body. A different isoform, called the kidney-specific WNK1 protein or KS-WNK1, is found only in kidney cells. The L-WNK1 and KS-WNK1 proteins act as kinases, which are enzymes that change the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions.

The L-WNK1 and KS-WNK1 proteins regulate channels in the cell membrane that control the transport of sodium or potassium into and out of cells. In the kidneys, sodium channels help transport sodium into specialized cells, which then transfer it into the blood. This transfer helps keep sodium in the body through a process called reabsorption. Potassium channels handle excess potassium that has been transferred from the blood into kidney cells. The channels transport potassium out of the cells in a process called secretion, so that it can be removed from the body in urine.

The L-WNK1 protein increases sodium reabsorption and decreases potassium secretion, whereas the KS-WNK1 protein has the opposite effect. Sodium and potassium are important for regulating blood pressure, and a balance of L-WNK1 protein and KS-WNK1 protein in the kidneys helps maintain the correct levels of sodium and potassium for healthy blood pressure.

Another isoform produced from the WNK1 gene, called the WNK1/HSN2 protein, is found in the cells of the nervous system, including nerve cells that transmit the sensations of pain, temperature, and touch (sensory neurons). The WNK1/HSN2 protein appears to regulate channels in the cell membrane that can transport negatively charged chlorine atoms (chloride ions). These channels maintain the proper amount of chloride inside cells, which is important for controlling the activation (excitation) of the neurons.

Source: MedlinePlus, National Library of Medicine. Source publication: 2023-05-08. Source review: 2017-04.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
neuropathy, hereditary sensory and autonomic, type 2AMONDO:0024309 · Evaluated 2023-05-05	Autosomal recessive	DefinitiveCharcot-Marie-Tooth Disease Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 2,496
Submissions for variants in or overlapping this gene: 3,955
Submissions explicitly reporting this gene: 3,824
Alleles reported pathogenic / likely pathogenic: 80
VariationIDs with uncertain significance: 1,345
VariationIDs with conflicting classifications: 101

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about WNK1?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 80 alleles in WNK1 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in WNK1.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

Buy BioDecode See a sample report →Check file compatibility →