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

KL gene

The KL gene provides instructions for producing the alpha-klotho protein, which is essential for regulating phosphate levels in the body.

Normal Function

The KL gene provides instructions for making the protein alpha-klotho, which is found primarily in kidney cells. This protein plays a major role in regulating the phosphate levels within the body (phosphate homeostasis). Phosphate is critical for the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys, which rid the body of excess phosphate by excreting it in urine or reabsorbing it into the bloodstream when needed.

Alpha-klotho attaches to and activates a protein called FGF receptor 1, which spans the membrane of many cell types, including kidney cells. Once the receptor is active, another protein called fibroblast growth factor 23 can bind to it. This binding stimulates signaling that stops phosphate reabsorption into the bloodstream.

Health Conditions Related to Genetic Changes

Hyperphosphatemic familial tumoral calcinosis

At least one mutation in the KL gene has been found to cause hyperphosphatemic familial tumoral calcinosis (HFTC), a condition characterized by an increase in the levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues.

  • The mutation replaces the amino acid histidine with arginine at position 193 (His193Arg or H193R).
  • This results in a shortage of functional alpha-klotho.
  • Consequently, FGF receptor 1 is not activated and cannot bind to fibroblast growth factor 23.
  • Because the signaling to stop phosphate reabsorption is disrupted, too much phosphate is reabsorbed into the bloodstream, leading to hyperphosphatemia and subsequent calcinosis.

Genomic Location

The KL gene is found on chromosome 13.

Frequently Asked Questions

Yes. Limiting dietary phosphate—found in dairy, nuts, processed foods, and certain meats—can reduce serum phosphate spikes. Consuming foods low in phosphate additives, such as fresh fruits and vegetables, and using phosphate‑free or low‑phosphate processed foods can help. Adequate hydration and regular exercise also support kidney function, which is crucial for phosphate excretion. Patients should work with a dietitian to create a balanced, low‑phosphate meal plan.
Patients with a KL gene mutation often develop painful, hard lumps under the skin, especially around the hips, elbows, or knees. These calcified deposits can cause swelling, redness, and limited joint movement. Other signs include unexplained fatigue, bone pain, or recurrent infections at the sites of calcinosis. If these symptoms appear, especially in a child or young adult, a clinician should consider checking serum phosphate levels and ordering a genetic test for KL mutations.
Diagnosis begins with a physical exam and measurement of serum phosphate and calcium. Imaging studies such as X‑ray, CT, or MRI can reveal characteristic calcified masses. A definitive diagnosis requires genetic testing—usually a targeted sequencing panel for the KL gene—to identify pathogenic variants like His193Arg (H193R). Some labs also perform whole‑exome sequencing if the panel is negative but clinical suspicion remains high.
Management focuses on lowering serum phosphate. Oral phosphate binders (e.g., calcium carbonate, sevelamer) are taken with meals to reduce absorption. In severe cases, low‑phosphate diets, frequent monitoring, and sometimes intravenous phosphate‑lowering agents or dialysis may be needed. Because the underlying defect is in the KL gene, gene‑therapy approaches are still experimental and not yet standard care.
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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