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SLC34A1 gene

solute carrier family 34 member 1
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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, which is characterized by high levels of calcium in the blood (hypercalcemia) and urine (hypercalciuria) and deposits of calcium in the kidneys (nephrocalcinosis). Individuals with this form of idiopathic infantile hypercalcemia also have 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, although some affected individuals do not develop signs and symptoms of the condition until adulthood. Features in affected adults, whether they had symptoms in infancy or not, typically include hypercalciuria, nephrocalcinosis, and kidney stones (nephrolithiasis).

The SLC34A1 gene mutations that cause infantile hypercalcemia 2 lead to production of an altered NaPi-IIa channel that cannot transport phosphate across kidney cell membranes. As a result, phosphate reabsorption is reduced and phosphate levels in the body are low.

Phosphate homeostasis is also controlled by vitamin D. When turned on (active), this vitamin stimulates the absorption of both phosphate and calcium from the intestines into the bloodstream. In an effort to raise the low phosphate levels caused by the loss of functional NaPi-IIa channels, vitamin D is activated. Too much active vitamin D increases calcium absorption into the bloodstream, causing hypercalcemia in affected individuals. The abnormal balance of calcium leads to high levels of the mineral in urine and can result in deposition of calcium in kidney tissue and the formation of kidney stones.

More About This Health Condition

Other disorders

Mutations in the SLC34A1 gene can cause several other health conditions with a variety of signs and symptoms related to hypophosphatemia. As in infantile hypercalcemia (described above), the gene mutations that cause these health conditions prevent the NaPi-IIa transporter from functioning, reducing phosphate absorption in the kidneys and causing hypophosphatemia. Some people with these mutations, diagnosed with hypophosphatemic nephrolithiasis/osteoporosis 1, have nephrolithiasis or low bone mineral density (osteoporosis). Others, diagnosed with Fanconi renotubular syndrome 2, develop problems with kidney function and hypophosphatemic rickets, a bone disorder that often causes bone pain and bowed legs. It is unclear why mutations in this gene lead to different sets of signs and symptoms.

Other Names for This Gene

  • FRTS2
  • HCINF2
  • Na(+)-dependent phosphate cotransporter 2A
  • Na(+)/Pi cotransporter 2A
  • Na+-phosphate cotransporter type II
  • naPi-2a
  • NAPI-3
  • NPHLOP1
  • NPT2
  • NPTIIa
  • renal sodium-dependent phosphate transporter
  • SLC11
  • SLC17A2
  • sodium-dependent phosphate transport protein 2A isoform 1
  • sodium-dependent phosphate transport protein 2A isoform 2
  • sodium-phosphate transport protein 2A
  • sodium/phosphate co-transporter
  • sodium/phosphate cotransporter 2A
  • solute carrier family 17 (sodium phosphate), member 2
  • solute carrier family 34 (sodium phosphate), member 1
  • solute carrier family 34 (type II sodium/phosphate cotransporter), member 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Research Resources

References

  • Kido S, Kaneko I, Tatsumi S, Segawa H, Miyamoto K. Vitamin D and type II sodium-dependent phosphate cotransporters. Contrib Nephrol. 2013;180:86-97. doi: 10.1159/000346786. Epub 2013 May 6. Review. Citation on PubMed
  • Magen D, Berger L, Coady MJ, Ilivitzki A, Militianu D, Tieder M, Selig S, Lapointe JY, Zelikovic I, Skorecki K. A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome. N Engl J Med. 2010 Mar 25;362(12):1102-9. doi: 10.1056/NEJMoa0905647. Citation on PubMed
  • Prié D, Huart V, Bakouh N, Planelles G, Dellis O, Gérard B, Hulin P, Benqué-Blanchet F, Silve C, Grandchamp B, Friedlander G. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002 Sep 26;347(13):983-91. Citation on PubMed
  • Pronicka E, Ciara E, Halat P, Janiec A, Wójcik M, Rowińska E, Rokicki D, Płudowski P, Wojciechowska E, Wierzbicka A, Książyk JB, Jacoszek A, Konrad M, Schlingmann KP, Litwin M. Biallelic mutations in CYP24A1 or SLC34A1 as a cause of infantile idiopathic hypercalcemia (IIH) with vitamin D hypersensitivity: molecular study of 11 historical IIH cases. J Appl Genet. 2017 Aug;58(3):349-353. doi: 10.1007/s13353-017-0397-2. Epub 2017 May 3. Citation on PubMed or Free article on PubMed Central
  • Schlingmann KP, Ruminska J, Kaufmann M, Dursun I, Patti M, Kranz B, Pronicka E, Ciara E, Akcay T, Bulus D, Cornelissen EA, Gawlik A, Sikora P, Patzer L, Galiano M, Boyadzhiev V, Dumic M, Vivante A, Kleta R, Dekel B, Levtchenko E, Bindels RJ, Rust S, Forster IC, Hernando N, Jones G, Wagner CA, Konrad M. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia. J Am Soc Nephrol. 2016 Feb;27(2):604-14. doi: 10.1681/ASN.2014101025. Epub 2015 Jun 5. Citation on PubMed or Free article on PubMed Central
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