SLC34A3

Summary

Gene Symbol: SLC34A3
Description: solute carrier family 34 member 3
Alias: HHRH, NPTIIc, sodium-dependent phosphate transport protein 2C, Na(+)-dependent phosphate cotransporter 2C, Na(+)/Pi cotransporter 2C, naPi-2c, sodium-phosphate transport protein 2C, sodium/inorganic phosphate cotransporter IIC, solute carrier family 34 (sodium phosphate), member 3, solute carrier family 34 (type II sodium/phosphate cotransporter), member 3, type IIc Na+/Pi cotransporter
Species: human
Products:     SLC34A3

Top Publications

  1. Forster I, Hernando N, Biber J, Murer H. Proximal tubular handling of phosphate: A molecular perspective. Kidney Int. 2006;70:1548-59 pubmed
    ..for three Na+-dependent phosphate (P i) cotransporter proteins, two of which (NaPi-IIa/SLC34A1 and NaPi-IIc/SLC34A3) control renal reabsorption of P i in the proximal tubule of mammals, whereas NaPi-IIb/SCLC34A2 mediates P i ..
  2. Yamamoto T, Michigami T, Aranami F, Segawa H, Yoh K, Nakajima S, et al. Hereditary hypophosphatemic rickets with hypercalciuria: a study for the phosphate transporter gene type IIc and osteoblastic function. J Bone Miner Metab. 2007;25:407-13 pubmed
    Two cases of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) were reported in Japanese female siblings...
  3. Bergwitz C, Roslin N, Tieder M, Loredo Osti J, Bastepe M, Abu Zahra H, et al. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet. 2006;78:179-92 pubmed
    ..The disease mapped to a 1.6-Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaP(i)-IIc...
  4. Lorenz Depiereux B, Benet Pages A, Eckstein G, Tenenbaum Rakover Y, Wagenstaller J, Tiosano D, et al. Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet. 2006;78:193-201 pubmed
    ..The candidate region contained a sodium-phosphate cotransporter gene, SLC34A3, which has been shown to be expressed in proximal tubulus cells...
  5. Schönauer R, Petzold F, Lucinescu W, Seidel A, Muller L, Neuber S, et al. Evaluating pathogenicity of SLC34A3-Ser192Leu, a frequent European missense variant in disorders of renal phosphate wasting. Urolithiasis. 2019;: pubmed publisher
    Loss-of-function mutations of SLC34A3 represent an established cause of a distinct renal phosphate wasting disorder termed hereditary hypophosphatemic rickets with hypercalciuria (HHRH)...
  6. Ichikawa S, Tuchman S, Padgett L, Gray A, Baluarte H, Econs M. Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. Bone. 2014;59:53-6 pubmed publisher
    ..HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc...
  7. Hasani Ranjbar S, Ejtahed H, Amoli M, Bitarafan F, Qorbani M, Soltani A, et al. SLC34A3 Intronic Deletion in an Iranian Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria. J Clin Res Pediatr Endocrinol. 2018;10:343-349 pubmed publisher
    ..profile results and gene analysis of 12 members of a family of a patient previously diagnosed with HHRH due to SLC34A3 mutation. Ten healthy controls were also evaluated...
  8. Levi M, Gratton E. Visualizing the regulation of SLC34 proteins at the apical membrane. Pflugers Arch. 2019;471:533-542 pubmed publisher
    The cloning of the renal NaPi-2a (SLC34A1) and NaPi-2c (SLC34A3) phosphate transporters has made it possible to characterize the molecular and biophysical regulation of renal proximal tubular reabsorption of inorganic phosphate (Pi)...
  9. Fujii T, Shiozaki Y, Segawa H, Nishiguchi S, Hanazaki A, Noguchi M, et al. Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney. Clin Exp Nephrol. 2019;23:313-324 pubmed publisher
    ..Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by loss-of-function mutations in the IIc Na+-dependent Pi transporter (NPT2c/Npt2c/NaPi-IIc) ..

More Information

Publications36

  1. Bai Y, Liu N, Shao M, Qin G, Gao X, Kong X. [Mutation analysis of four pedigrees affected with hypophosphatemic rickets through targeted next-generation sequencing]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018;35:638-643 pubmed publisher
    ..The coding regions and exon/intron boundaries of PHEX, FGF23, DMP1, ENPP1, CLCN5 and SLC34A3 genes of the probands were analyzed by targeted next-generation sequencing (NGS)...
  2. Muscher Banse A, Breves G. Mechanisms and regulation of epithelial phosphate transport in ruminants: approaches in comparative physiology. Pflugers Arch. 2019;471:185-191 pubmed publisher
    ..plasma Pi is mainly mediated by the Pi transporters NaPi IIa (SLC34A1) and NaPi IIc (SLC34A3) in proximal tubule apical cells...
  3. Bergwitz C, Miyamoto K. Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy. Pflugers Arch. 2019;471:149-163 pubmed publisher
    Hereditary hypophosphatemic rickets with hypercalciuria (HHRH; OMIM: 241530) is a rare autosomal recessive disorder with an estimated prevalence of 1:250,000 that was originally described by Tieder et al...
  4. Acar S, BinEssa H, Demir K, Al Rijjal R, Zou M, Catli G, et al. Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3. PLoS ONE. 2018;13:e0193388 pubmed publisher
    ..sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions...
  5. Goldsweig B, Carpenter T. Hypophosphatemic rickets: lessons from disrupted FGF23 control of phosphorus homeostasis. Curr Osteoporos Rep. 2015;13:88-97 pubmed publisher
    ..disorders with FGF23-independent hypophosphatemia, specifically hypophosphatemic rickets with hypercalciuria (HHRH). Errant diagnosis of hypophosphatemic disorders is common...
  6. Guven A, Al Rijjal R, BinEssa H, Dogan D, Kor Y, Zou M, et al. Mutational analysis of PHEX, FGF23 and CLCN5 in patients with hypophosphataemic rickets. Clin Endocrinol (Oxf). 2017;87:103-112 pubmed publisher
    ..of rare hereditary renal phosphate wasting disorders caused by mutations in PHEX, FGF23, DMP1, ENPP1, CLCN5 or SLC34A3. To investigate underlying genetic defects in patients with hypophosphataemic rickets...
  7. Marangella M, Marcuccio C, Vitale C. [Genetic approach to nephrolithiasis]. G Ital Nefrol. 2015;32 Suppl 64: pubmed
    ..calcium sensing receptor mutations, familial hypopomagnesiemic hypercalciuria (FHHNC), hypophosphatemic rickets (HHRH), renal tubular acidosis (dRTA), primary hyperoxaluria (PH), cystinuria, 2-8 dihydroxyadeninuria (2-8 DHA)...
  8. Ma S, Vega Warner V, Gillies C, Sampson M, Kher V, Sethi S, et al. Whole Exome Sequencing Reveals Novel PHEX Splice Site Mutations in Patients with Hypophosphatemic Rickets. PLoS ONE. 2015;10:e0130729 pubmed publisher
    ..by mutations in the PHEX gene located on the X-chromosome or by mutations in CLCN5, DMP1, ENPP1, FGF23, and SLC34A3. The aims of this study were to perform molecular diagnostics for four patients with HR of Indian origin (two ..
  9. Wagner C, Rubio Aliaga I, Hernando N. Renal phosphate handling and inherited disorders of phosphate reabsorption: an update. Pediatr Nephrol. 2019;34:549-559 pubmed publisher
    ..phosphate transporters located in the brush border membrane of the proximal tubule: NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2)...
  10. Yagi S, Shiojiri N. Identification of novel genetic markers for mouse yolk sac cells by using microarray analyses. Placenta. 2017;49:68-71 pubmed publisher
    ..Apoa4, Lrp2, Fxyd2, Slc34a3 and Entpd2 were predominantly expressed in VYS epithelial cells...
  11. Dinour D, Davidovits M, Ganon L, Ruminska J, Forster I, Hernando N, et al. Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency. Pediatr Nephrol. 2016;31:2289-2297 pubmed
    ..The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly...
  12. Shiozaki Y, Segawa H, Ohnishi S, Ohi A, Ito M, Kaneko I, et al. Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells. J Med Invest. 2015;62:209-18 pubmed publisher
    NaPi-IIc/SLC34A3 is a sodium-dependent inorganic phosphate (Pi) transporter in the renal proximal tubules and its mutations cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH)...
  13. Rafaelsen S, Johansson S, Ræder H, Bjerknes R. Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol. 2016;174:125-36 pubmed publisher
    ..Patients with hypercalcuria were screened for SLC34A3 mutations. In one family, exome sequencing was performed...
  14. Areses Trapote R, López García J, Ubetagoyena Arrieta M, Eizaguirre A, Sáez Villaverde R. Hereditary hypophosphatemic rickets with hypercalciuria: case report. Nefrologia. 2012;32:529-34 pubmed publisher
    ..The molecular study found a change in homozygosity in intron 5 of gene SLC34A3 (NM_080877.2:c[ 448 +5G>A] + [ 448 +5G>A] )...
  15. Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, et al. Growth-related renal type II Na/Pi cotransporter. J Biol Chem. 2002;277:19665-72 pubmed
    ..The finding of the present study suggest that the type IIc is a growth-related renal Na/P(i) cotransporter, which has a high affinity for P(i) and is electroneutral. ..
  16. Hasani Ranjbar S, Amoli M, Ebrahim Habibi A, Dehghan E, Soltani A, Amiri P, et al. SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria. J Clin Res Pediatr Endocrinol. 2012;4:89-93 pubmed publisher
    ..In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter...
  17. Braithwaite V, Pettifor J, Prentice A. Novel SLC34A3 mutation causing hereditary hypophosphataemic rickets with hypercalciuria in a Gambian family. Bone. 2013;53:216-20 pubmed publisher
    ..The mother and clinically unaffected siblings had largely normal biochemistry. Genetic analysis of the SLC34A3 gene, encoding the type IIc sodium-phosphate cotransporter, in DNA samples from the siblings and their mother was ..
  18. Dhir G, Li D, Hakonarson H, Levine M. Late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH) due to mutation of SLC34A3/NPT2c. Bone. 2017;97:15-19 pubmed publisher
    ..We performed biochemical studies and sequenced the SLC34A3 gene using genomic DNA from peripheral blood mononuclear cells...
  19. Abe Y, Nagasaki K, Watanabe T, Abe T, Fukami M. Association between compound heterozygous mutations of SLC34A3 and hypercalciuria. Horm Res Paediatr. 2014;82:65-71 pubmed publisher
    Mutations in SLC34A3 have been shown to cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH)...
  20. Tencza A, Ichikawa S, Dang A, Kenagy D, McCarthy E, Econs M, et al. Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/type IIc sodium-phosphate cotransporter: presentation as hypercalciuria and nephrolithiasis. J Clin Endocrinol Metab. 2009;94:4433-8 pubmed publisher
    ..rickets with hypercalciuria (HHRH) is a metabolic disorder due to homozygous loss-of-function mutations in the SLC34A3 gene encoding the renal type IIc sodium-phosphate cotransporter (NaPi-IIc)...
  21. Jaureguiberry G, Carpenter T, Forman S, Juppner H, Bergwitz C. A novel missense mutation in SLC34A3 that causes hereditary hypophosphatemic rickets with hypercalciuria in humans identifies threonine 137 as an important determinant of sodium-phosphate cotransport in NaPi-IIc. Am J Physiol Renal Physiol. 2008;295:F371-9 pubmed publisher
    ..410C>T(p.T137M) (T137M) on the maternal and g.4225_50del on the paternal allele of SLC34A3, in a previously reported male with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and recurrent ..
  22. Pesta D, Tsirigotis D, Befroy D, Caballero D, Jurczak M, Rahimi Y, et al. Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB J. 2016;30:3378-3387 pubmed
    ..Similar findings were observed in a patient with chronic hypophosphatemia as a result of a mutation in SLC34A3 who had a 50% reduction in both serum Pi content and muscle VATP After oral Pi ..
  23. Ehnes C, Forster I, Bacconi A, Kohler K, Biber J, Murer H. Structure-function relations of the first and fourth extracellular linkers of the type IIa Na+/Pi cotransporter: II. Substrate interaction and voltage dependency of two functionally important sites. J Gen Physiol. 2004;124:489-503 pubmed
    ..The simulations predict that cys substitution at Gly-134 or cys modification of Cys-533 alters the preferred orientation of the empty carrier from an inward to outward-facing conformation for hyperpolarizing voltages. ..
  24. Gisler S, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin L, et al. PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. Kidney Int. 2003;64:1733-45 pubmed
    ..We hypothesize that PDZK1 and NHERF-1 establish an extended network beneath the apical membrane to which membrane proteins and regulatory components are anchored. ..
  25. Dasgupta D, Wee M, Reyes M, Li Y, Simm P, Sharma A, et al. Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol. 2014;25:2366-75 pubmed publisher
    Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na(+))-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with ..
  26. Yu Y, Sanderson S, Reyes M, Sharma A, Dunbar N, Srivastava T, et al. Novel NaPi-IIc mutations causing HHRH and idiopathic hypercalciuria in several unrelated families: long-term follow-up in one kindred. Bone. 2012;50:1100-6 pubmed publisher
    Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-..
  27. Haito Sugino S, Ito M, Ohi A, Shiozaki Y, Kangawa N, Nishiyama T, et al. Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria. Am J Physiol Cell Physiol. 2012;302:C1316-30 pubmed publisher
    Mutations in the apically located Na(+)-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH)...