| Tbio | Claudin-16 |
Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Involved in paracellular magnesium reabsorption. Required for a selective paracellular conductance. May form, alone or in partnership with other constituents, an intercellular pore permitting paracellular passage of magnesium and calcium ions down their electrochemical gradients. Alternatively, it could be a sensor of magnesium concentration that could alter paracellular permeability mediated by other factors.
Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]
Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]
Comments
| Disease | Target Count |
|---|---|
| HYPERCALCIURIA, CHILDHOOD, SELF-LIMITING | 1 |
| Primary hypomagnesemia (disorder) | 2 |
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6685 | 4.4911933745588E-49 |
| ovarian cancer | 8492 | 2.0534372986142E-5 |
| Disease | Target Count |
|---|---|
| renal hypomagnesemia 3 | 2 |
| Disease | Target Count |
|---|---|
| Hypomagnesemia 3 | 1 |
| Accession | Q9Y5I7 |
| Symbols |
HOMG3 PCLN1 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Platypus | EggNOG Inparanoid |
| Chicken | OMA Inparanoid |
| Anole lizard | OMA EggNOG Inparanoid |
| Xenopus | OMA EggNOG Inparanoid |
| PMID | Text |
|---|---|
| 25557732 | 1,25(OH)2 VitD transcriptionally inhibits renal claudin-16 expression by a mechanism sensitive to CaSR and Mg(2+). |
| 25477417 | CLDN16 mutations are associated with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. |
| 24659781 | These results suggest that STX8 mediates the recycling of CLDN16 and constitutes an important component of the CLDN16 trafficking machinery in the kidney. |
| 24321194 | A novel CLDN16 mutation has been identified in a large consanguineous family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. |
| 22422540 | Six different mutations of CLDN16 were detected (five missense and one nonsense); three of the missense mutations were previously unknown (p.Cys80Tyr, p.Lys183Glu, and p.Gly233Arg). |
| 21848011 | Claudin 16 gene revealed homozygosity for the p.K183E(AAA>GAA) C. 547A>G indicating the diagnosis of hypomagnesemia with hypercalciuria and nephrocalcinosis. |
| 21717372 | Claudin-16 plays a role beyond that of an initial metastasis repressor in breast cancer. |
| 21669885 | A novel mutation of CLDN16 gene is responsible for familial hypomagnesaemia in Turkish children. |
| 21186073 | Multiple distinct mutations in the CLDN16 and CLDN19 genes have been found responsible for familial hypomagnesemia with hypercalciuria and nephrocalcinosis. |
| 20664984 | Elevated CLDN16 gene expression was suggested to be involved in the development of breast cancer and to be a biomarker and target treatment for breast cancer. |
| More... |
MTSRTPLLVTACLYYSYCNSRHLQQGVRKSKRPVFSHCQVPETQKTDTRHLSGARAGVCPCCHPDGLLAT 1 - 70 MRDLLQYIACFFAFFSAGFLIVATWTDCWMVNADDSLEVSTKCRGLWWECVTNAFDGIRTCDEYDSILAE 71 - 140 HPLKLVVTRALMITADILAGFGFLTLLLGLDCVKFLPDEPYIKVRICFVAGATLLIAGTPGIIGSVWYAV 141 - 210 DVYVERSTLVLHNIFLGIQYKFGWSCWLGMAGSLGCFLAGAVLTCCLYLFKDVGPERNYPYSLRKAYSAA 211 - 280 GVSMAKSYSAPRTETAKMYAVDTRV 281 - 305 //
| PMID | Year | Title |
|---|---|---|
| 25557732 | 2015 | The claudin-16 channel gene is transcriptionally inhibited by 1,25-dihydroxyvitamin D. |
| 25477417 | 2015 | Retrospective cohort study of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis due to CLDN16 mutations. |
| 24659781 | 2014 | Tight junctional localization of claudin-16 is regulated by syntaxin 8 in renal tubular epithelial cells. |
| 24321194 | 2013 | A novel CLDN16 mutation in a large family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. |
| 22422540 | 2012 | Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations. |
| 22373575 | 2012 | Claudin-14 regulates renal Ca?? transport in response to CaSR signalling via a novel microRNA pathway. |
| 21848011 | 2011 | A novel mutation of the claudin 16 gene in familial hypomagnesemia with hypercalciuria and nephrocalcinosis mimicking rickets. |
| 21717372 | 2011 | Claudin-16/paracellin-1, cloning, expression, and its role in tight junction functions in cancer and endothelial cells. |
| 21669885 | 2012 | Clinical and molecular characterization of Turkish patients with familial hypomagnesaemia: novel mutations in TRPM6 and CLDN16 genes. |
| 21186073 | 2011 | The role of tight junctions in paracellular ion transport in the renal tubule: lessons learned from a rare inherited tubular disorder. |
| More... |
