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CLCN5 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

CLCN5 gene

The CLCN5 gene provides instructions for a protein that regulates acidity and protein reabsorption in the kidneys, playing a critical role in preventing protein loss in urine.

Normal Function

The CLCN5 gene provides instructions for making a protein that transports charged molecules (ions) across cell membranes. Specifically, the CLCN5 protein exchanges negatively charged chloride ions for positively charged hydrogen ions.

The CLCN5 protein is found primarily in structures called proximal tubules in the kidneys. The proximal tubules help to reabsorb protein and other important substances back into the bloodstream. Substances that are not reabsorbed by the kidneys are released into the urine. Thus, the CLCN5 protein helps prevent protein loss in the urine (proteinuria).

Within proximal tubular cells, the CLCN5 protein is found in specialized compartments called endosomes. Endosomes at the proximal tubular cell surface are involved in the reabsorption of proteins. They also help transport proteins and other molecules to their proper locations within the cell. The process of transporting proteins from the outer cell membrane to the inside of the cell is called endocytosis.

By transporting hydrogen ions into endosomes and chloride ions out, the CLCN5 protein helps endosomes maintain the proper acidity level (pH). Endosomal pH levels must be acidic for the proximal tubular cells to function properly.

Health Conditions Related to Genetic Changes

Dent disease

Changes in the CLCN5 gene can cause a type of Dent disease called Dent disease 1. Genetic changes that cause disease are called pathogenic variants. Dent disease 1 occurs almost exclusively in males. This condition is characterized by chronic kidney disease that can lead to kidney failure and other health problems. Many of the pathogenic variants that are associated with Dent disease 1 cause cells to make a version of the protein that does not function properly. This impairs the regulation of endosomal pH and disrupts endocytosis and protein reabsorption in the proximal tubules. As a result, proteins and nutrients that should be reabsorbed into the bloodstream are released in the urine.

Other Names for This Gene

  • ClC-5
  • CLC5
  • Dent disease
  • DENTS
  • hCIC-K2
  • XLRH
  • XRN

Frequently Asked Questions

The first clues are often subtle protein in the urine (proteinuria) that can be detected on a routine urine test, sometimes accompanied by low levels of calcium in the blood (hypocalcemia) or mild swelling (edema). Parents should watch for persistent fatigue, growth delays, or frequent urinary tract infections, and have a pediatric nephrologist evaluate any abnormal urine findings.
Dent disease 1 is inherited in an X‑linked recessive manner, meaning it mainly affects males, while carrier females may have milder symptoms. Female relatives of affected males should consider genetic counseling and testing, especially if they plan to have children, to determine carrier status and assess risk for future offspring.
The mutation disrupts chloride/hydrogen ion exchange in kidney tubules, impairing protein reabsorption and causing chronic protein loss. Over time, this damages the tubules and can progress to chronic kidney disease. Early interventions include strict blood pressure control, limiting high-protein diets, using medications like ACE inhibitors or ARBs to reduce proteinuria, and regular monitoring of kidney function to catch decline early.
Preparation involves a blood draw after fasting is usually not required; the lab will sequence the CLCN5 gene. A positive result confirms the diagnosis, allowing targeted management: close monitoring of kidney function, early initiation of renoprotective therapy, and counseling on lifestyle changes. It also informs family planning decisions and enables early screening of at-risk relatives.
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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