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Gene Review

CLDN16  -  claudin 16

Homo sapiens

Synonyms: Claudin-16, HOMG3, PCLN-1, PCLN1, Paracellin-1
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Disease relevance of CLDN16


High impact information on CLDN16


Chemical compound and disease context of CLDN16


Biological context of CLDN16

  • Thus, mutations at different intragenic sites in the claudin 16 gene may lead to particular clinical phenotypes with a distinct prognosis [9].
  • Genotype analysis revealed PCLN-1 mutations in all except three mutant alleles (94%) [5].
  • Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene [11].
  • Extensive total-genome haplotype analysis revealed homozygosity in one family, in the region of the PCLN1 gene [12].
  • Blocking clathrin-mediated endocytosis increases surface expression of Cldn16 L203X [13].

Anatomical context of CLDN16


Associations of CLDN16 with chemical compounds

  • We hypothesize that in the thick ascending limb of the nephron, paracellin-1 dysfunction, with a concomitant loss of cation selectivity, could contribute to the dissipation of the lumen-positive potential that is the driving force for the reabsorption of Mg2+ [2].
  • Since claudin 16 functions as a paracellular channel for Mg(2+), its diffuse pattern in preeclamptic placentae suggests the altered paracellular transport of Mg(2+) between the maternal blood and the placental tissue [14].
  • Hydrochlorothiazide in CLDN16 mutation [8].
  • The degradation of dephosphorylated PCLN-1 and S217A mutant was inhibited by chloroquine, a specific lysosome inhibitor [16].
  • PKA inhibitors, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) and myristoylated protein kinase A inhibitor 14-22 amide PKI, and an adenylate cyclase inhibitor, 2',5'-dideoxy adenosine (DDA), reduced the phosphoserine level of PCLN-1 [16].

Other interactions of CLDN16


Analytical, diagnostic and therapeutic context of CLDN16

  • Mouse multiple-tissue Northern blot showed Pcln1 expression exclusively in the kidney [19].
  • The identification and characterization of the rodent Pcln1 genes provide the basis for further studies of paracellin-1 function in suitable animal models [19].
  • Cldn-16 transcripts were also identified by RT-PCR [20].
  • As the first step to clarify these roles, we examined the expression and distribution of claudin-16 and several other major claudin subtypes, claudins 1-4 and 10, in bovine renal tubular segments by immunofluorescence microscopy [21].
  • Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%) [22].


  1. Exclusion of mutations in FXYD2, CLDN16 and SLC12A3 in two families with primary renal Mg2+ loss. Meij, I.C., van den Heuvel, L.P., Hemmes, S., van der Vliet, W.A., Willems, J.L., Monnens, L.A., Knoers, N.V. Nephrol. Dial. Transplant. (2003) [Pubmed]
  2. Paracellin-1 and the modulation of ion selectivity of tight junctions. Hou, J., Paul, D.L., Goodenough, D.A. J. Cell. Sci. (2005) [Pubmed]
  3. Unusual clinical presentation and possible rescue of a novel claudin-16 mutation. Müller, D., Kausalya, P.J., Bockenhauer, D., Thumfart, J., Meij, I.C., Dillon, M.J., van't Hoff, W., Hunziker, W. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  4. Paracellin-1 gene mutation with multiple congenital abnormalities. Türkmen, M., Kasap, B., Soylu, A., Böber, E., Konrad, M., Kavukçu, S. Pediatr. Nephrol. (2006) [Pubmed]
  5. Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Weber, S., Schneider, L., Peters, M., Misselwitz, J., Rönnefarth, G., Böswald, M., Bonzel, K.E., Seeman, T., Suláková, T., Kuwertz-Bröking, E., Gregoric, A., Palcoux, J.B., Tasic, V., Manz, F., Schärer, K., Seyberth, H.W., Konrad, M. J. Am. Soc. Nephrol. (2001) [Pubmed]
  6. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Simon, D.B., Lu, Y., Choate, K.A., Velazquez, H., Al-Sabban, E., Praga, M., Casari, G., Bettinelli, A., Colussi, G., Rodriguez-Soriano, J., McCredie, D., Milford, D., Sanjad, S., Lifton, R.P. Science (1999) [Pubmed]
  7. Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16. Kausalya, P.J., Amasheh, S., Günzel, D., Wurps, H., Müller, D., Fromm, M., Hunziker, W. J. Clin. Invest. (2006) [Pubmed]
  8. Hydrochlorothiazide in CLDN16 mutation. Zimmermann, B., Plank, C., Konrad, M., Stöhr, W., Gravou-Apostolatou, C., Rascher, W., Dötsch, J. Nephrol. Dial. Transplant. (2006) [Pubmed]
  9. A novel claudin 16 mutation associated with childhood hypercalciuria abolishes binding to ZO-1 and results in lysosomal mistargeting. Müller, D., Kausalya, P.J., Claverie-Martin, F., Meij, I.C., Eggert, P., Garcia-Nieto, V., Hunziker, W. Am. J. Hum. Genet. (2003) [Pubmed]
  10. An Unusual Patient with Hypercalciuria, Recurrent Nephrolithiasis, Hypomagnesemia and G227R Mutation of Paracellin-1. An Unusual Patient with Hypercalciuria and Hypomagnesemia Unresponsive to Thiazide Diuretics. Kutluturk, F., Temel, B., Uslu, B., Aral, F., Azezli, A., Orhan, Y., Konrad, M., Ozbey, N. Horm. Res. (2006) [Pubmed]
  11. Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene. Weber, S., Hoffmann, K., Jeck, N., Saar, K., Boeswald, M., Kuwertz-Broeking, E., Meij, I.I., Knoers, N.V., Cochat, P., Suláková, T., Bonzel, K.E., Soergel, M., Manz, F., Schaerer, K., Seyberth, H.W., Reis, A., Konrad, M. Eur. J. Hum. Genet. (2000) [Pubmed]
  12. Mapping of gene loci for nephronophthisis type 4 and Senior-Løken syndrome, to chromosome 1p36. Schuermann, M.J., Otto, E., Becker, A., Saar, K., Rüschendorf, F., Polak, B.C., Ala-Mello, S., Hoefele, J., Wiedensohler, A., Haller, M., Omran, H., Nürnberg, P., Hildebrandt, F. Am. J. Hum. Genet. (2002) [Pubmed]
  13. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: blocking endocytosis restores surface expression of a novel Claudin-16 mutant that lacks the entire C-terminal cytosolic tail. Müller, D., Kausalya, P.J., Meij, I.C., Hunziker, W. Hum. Mol. Genet. (2006) [Pubmed]
  14. Endothelia of term human placentae display diminished expression of tight junction proteins during preeclampsia. Liévano, S., Alarcón, L., Chávez-Munguía, B., González-Mariscal, L. Cell Tissue Res. (2006) [Pubmed]
  15. Genetic heterogeneity in familial renal magnesium wasting. Kantorovich, V., Adams, J.S., Gaines, J.E., Guo, X., Pandian, M.R., Cohn, D.H., Rude, R.K. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  16. Phosphorylation of paracellin-1 at Ser217 by protein kinase A is essential for localization in tight junctions. Ikari, A., Matsumoto, S., Harada, H., Takagi, K., Hayashi, H., Suzuki, Y., Degawa, M., Miwa, M. J. Cell. Sci. (2006) [Pubmed]
  17. A novel locus for autosomal dominant nonsyndromic hearing loss (DFNA44) maps to chromosome 3q28-29. Modamio-Høybjør, S., Moreno-Pelayo, M.A., Mencía, A., del Castillo, I., Chardenoux, S., Armenta, D., Lathrop, M., Petit, C., Moreno, F. Hum. Genet. (2003) [Pubmed]
  18. Inherited hypercalciuric syndromes: Dent's disease (CLC-5) and familial hypomagnesemia with hypercalciuria (paracellin-1). Knohl, S.J., Scheinman, S.J. Semin. Nephrol. (2004) [Pubmed]
  19. Primary gene structure and expression studies of rodent paracellin-1. Weber, S., Schlingmann, K.P., Peters, M., Nejsum, L.N., Nielsen, S., Engel, H., Grzeschik, K.H., Seyberth, H.W., Gröne, H.J., Nüsing, R., Konrad, M. J. Am. Soc. Nephrol. (2001) [Pubmed]
  20. Identification of multiple claudins in the rat epididymis. Gregory, M., Cyr, D.G. Mol. Reprod. Dev. (2006) [Pubmed]
  21. Restricted localization of claudin-16 at the tight junction in the thick ascending limb of henle's loop together with claudins 3, 4, and 10 in bovine nephrons. Ohta, H., Adachi, H., Takiguchi, M., Inaba, M. J. Vet. Med. Sci. (2006) [Pubmed]
  22. Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. Lee, C.T., Lien, Y.H., Lai, L.W., Chen, J.B., Lin, C.R., Chen, H.C. Kidney Int. (2006) [Pubmed]
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