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SLC34A1 gene

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

SLC34A1 gene

The SLC34A1 gene provides instructions for making a protein essential for regulating phosphate levels in the body, and mutations in this gene are linked to various metabolic and kidney-related disorders.

Normal Function

The SLC34A1 gene provides instructions for making a protein called sodium-dependent phosphate transporter 2A (NaPi-IIa), which plays a role in the regulation of phosphate levels in the body (phosphate homeostasis). Phosphate is needed for many functions including the breakdown of substances (metabolic processes), signaling between cells, and the production of DNA building blocks (nucleotides) and fats. The NaPi-IIa protein is located in the membrane surrounding kidney cells, where it transports phosphate across the cell membrane. NaPi-IIa reabsorbs phosphate from urine back into the body when more of the mineral is needed.

Health Conditions Related to Genetic Changes

Idiopathic infantile hypercalcemia

At least 14 mutations in the SLC34A1 gene have been found to cause a type of idiopathic infantile hypercalcemia called infantile hypercalcemia 2. This condition is characterized by:

  • High levels of calcium in the blood (hypercalcemia) and urine (hypercalciuria)
  • Deposits of calcium in the kidneys (nephrocalcinosis)
  • Low levels of phosphate in the blood (hypophosphatemia)

The hypercalcemia typically causes vomiting, poor feeding, and an inability to grow and gain weight at the expected rate (failure to thrive) in infancy. In adults, features typically include hypercalciuria, nephrocalcinosis, and kidney stones (nephrolithiasis).

Mutations in this gene lead to an altered NaPi-IIa channel that cannot transport phosphate effectively. Because phosphate reabsorption is reduced, the body attempts to compensate by activating vitamin D. Excess active vitamin D increases calcium absorption into the bloodstream, leading to the abnormal calcium balance and kidney complications associated with the condition.

Other disorders

Mutations in the SLC34A1 gene can cause other health conditions related to hypophosphatemia, including:

  • Hypophosphatemic nephrolithiasis/osteoporosis 1: Characterized by kidney stones or low bone mineral density (osteoporosis).
  • Fanconi renotubular syndrome 2: Characterized by problems with kidney function and hypophosphatemic rickets, a bone disorder that often causes bone pain and bowed legs.

Frequently Asked Questions

Infantile hypercalcemia 2 typically presents in infancy with symptoms such as vomiting, poor feeding, dehydration, and failure to thrive. Infants may also appear irritable or lethargic. Diagnosis is usually made through blood tests that reveal high levels of calcium (hypercalcemia) and low levels of phosphate (hypophosphatemia). Urine tests may show high calcium levels (hypercalciuria). Imaging studies, such as ultrasound or CT scans, may be used to detect nephrocalcinosis, which is the deposition of calcium in the kidneys. Genetic testing for mutations in the SLC34A1 gene can confirm the diagnosis.
The SLC34A1 gene produces a protein that reabsorbs phosphate from the urine back into the bloodstream. When this protein is defective due to a mutation, the kidneys lose excessive phosphate, leading to low blood phosphate levels (hypophosphatemia). In response to low phosphate, the body activates vitamin D to try to increase phosphate absorption. However, active vitamin D also significantly increases the absorption of calcium from the gut and the release of calcium from bones. This compensatory mechanism results in high levels of calcium in the blood (hypercalcemia) and urine (hypercalciuria), which can lead to kidney stones and calcium deposits in the kidneys.
Long-term complications primarily affect the kidneys due to the persistent high levels of calcium in the urine. This can lead to nephrocalcinosis, where calcium deposits form in the kidney tissue, potentially causing scarring and impaired kidney function. Patients are also at a high risk for developing kidney stones (nephrolithiasis), which can cause pain, blockages, and further damage to the kidneys. Over time, chronic kidney disease may develop if the calcium deposits and stones are not managed effectively. Regular monitoring of kidney function and imaging is crucial to detect and manage these complications early.
Management often involves dietary modifications to help control calcium and phosphate levels. Patients may be advised to maintain adequate hydration to help flush calcium from the kidneys and reduce the risk of stone formation. Dietary calcium intake may need to be carefully balanced; while excessive calcium should be avoided, severe restriction is generally not recommended as it can worsen the body's compensatory mechanisms. Some patients may require phosphate supplementation to help correct hypophosphatemia, which can in turn help reduce the excessive activation of vitamin D and subsequent hypercalcemia. Individualized dietary plans should be developed in consultation with a metabolic specialist or dietitian.
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.