SLC34A3 Membrane Protein Introduction

Introduction of SLC34A3

Solute carrier family 34 member 3 (SLC34A3), also known as Sodium-phosphate transport protein 2C, Na(+)-dependent phosphate cotransporter 2C, and Na(+)/Pi cotransporter 2C (NaPi-2c), is a protein that in humans is encoded by the SLC34A3 gene. NaPi-2c (SLC34A3) consists of 599 amino acids. It is mostly expressed in the kidney like NaPi-2a. In the kidney, SLC34A3 is found in the brush border membrane of the early proximal tubule (S1 segment) of juxtamedullary nephrons and is absent from other portions of the proximal nephron. During phosphate depletion, SLC34A3 protein is also detected in the early proximal tubule of superficial nephrons. SLC34A3 may also be expressed in bone, but its function there has not been elucidated.

Basic Information of SLC34A3
Protein Name Sodium-dependent phosphate transport protein 2C
Gene Name SLC34A3
Aliases Sodium-phosphate transport protein 2C, Na(+)-dependent phosphate cotransporter 2C, Sodium/inorganic phosphate cotransporter IIC, Sodium/phosphate cotransporter 2C, Na(+)/Pi cotransporter 2C, NaPi-2c, Solute carrier family 34 member 3, NPT2C, NPTIIC
Organism Homo sapiens (Human)
UniProt ID Q8N130
Transmembrane Times 8
Length (aa) 599

Function of SLC34A3 Membrane Protein

Hereditary hypophosphatemic rickets with hypercalcuria (HHRH) is a rare autosomal recessive disorder caused by mutations in the SLC34A3 gene which encodes for SLC34A3. Patients suffer from hypophosphatemia due to loss of renal phosphate. Reduced availability of phosphate impairs bone mineralization and growth leading to rickets. Compensatory increases in 1,25-OH2 vitamin D3 synthesis and levels stimulate intestinal phosphate and calcium absorption. However, excessive calcium intake is offset by increased urinary excretion, with high urinary calcium levels and phosphate causing kidney stones and renal calcinosis. Patients with HHRH showed SLC34A3 deletions and truncations as well as splice site mutations, homozygous missense, or compound missense mutations.

Topology and structure-function features of SLC34 proteins. Fig.1 Topology and structure-function features of SLC34 proteins. (Wagner, 2014)

Application of SLC34A3 Membrane Protein in Literature

  1. Dasgupta D., et al. Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol. 2014, 25(10): 2366-75. PubMed ID: 24700880

    The article reveals that the mutations in SLC34A3/NPT2c are involved in the kidney stones and nephrocalcinosis.

  2. Abe Y., et al. Association between compound heterozygous mutations of SLC34A3 and hypercalciuria. Horm Res Paediatr. 2014, 82(1): 65-71. PubMed ID: 24924704

    The article reports a patient with compound heterozygous mutations of SLC34A3. Biallelic mutations in SLC34A3 can thus be associated with hypercalciuria not accompanied by rickets.

  3. Chi Y., et al. A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient. Bone. 2014, 59: 114-21. PubMed ID: 24246249

    The article reports that a compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient. This is the first report of HHRH in the Chinese population.

  4. Ichikawa S., et al. Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. Bone. 2014, 59: 53-6. PubMed ID: 24176905

    The article reports a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH.

  5. Hasani-Ranjbar S., et al. SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria. J Clin Res Pediatr Endocrinol. 2012, 4(2): 89-93. PubMed ID: 22672866

    Authors in this group found 101-bp deletion in intron 9 of the SLC34A3 gene, which is the first report for the presence of SLC34A3 intron 9 deletion in an Iranian population.

SLC34A3 Preparation Options

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  1. Wagner C A, et al. (2014). The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch. 466(1): 139-53.

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