Abstract
Background and Objectives: The defects in the CLDN16 gene are a cause of primary hypomagnesemia (FHHNC), which is characterized by massive renal magnesium wasting, resulting in nephrocalcinosis and renal failure. The mutations occur throughout the gene’s coding region and can impact on intracellular trafficking of the protein or its paracellular pore forming function. To gain more understanding about the mechanisms by which CLDN16 mutations can induce FHHNC, we performed an in-depth computational analysis of the CLDN16 gene and protein, focusing specifically on the prediction of the latter’s subcellular localization. Materials and Methods: The complete nucleotide or amino acid sequence of CLDN16 in FASTA format was entered and processed in 14 databases. Results: One CpG island was identified. Twenty five promoters/enhancers were predicted. The CLDN16 interactome was found to consist of 20 genes, mainly involved in kidney diseases. No signal peptide cleavage site was identified. A probability of export to mitochondria equal to 0.9740 and a cleavable mitochondrial localization signal in the N terminal of the CLDN16 protein were predicted. The secondary structure prediction was visualized. Νo phosphorylation sites were identified within the CLDN16 protein region by applying DISPHOS to the functional class of transport. The KnotProt database did not predict any knot or slipknot in the protein structure of CLDN16. Seven putative miRNA binding sites within the 3’-UTR region of CLDN16 were identified. Conclusions: This is the first study to identify mitochondria as a probable cytoplasmic compartment for CLDN16 localization, thus providing new insights into the protein’s intracellular transport. The results relative to the CLDN16 interactome underline its role in renal pathophysiology and highlight the functional dependence of CLDNs-10, 14, 16, 19. The predictions pertaining to the miRNAs, promoters/enhancers and CpG islands of the CLDN16 gene indicate a strict regulation of its expression both transcriptionally and post-transcriptionally.
Highlights
The CLDN16 gene is clustered on chromosome 3q28 and encodes the claudin16 protein which is found primarily in the kidneys, in the thick ascending limb (TAL) of the loop of Henle where it regulates the paracellular resorption of magnesium ions
Medicina 2019, 55, 409 renal magnesium wasting with hypomagnesemia and hypercalciuria resulting in nephrocalcinosis and renal failure (Entrez gene summary: https://www.ncbi.nlm.nih.gov/gene/10686)
One CpG island was identified in the nucleotide sequence of the CLDN16 gene (Figure 2)
Summary
The CLDN16 gene is clustered on chromosome 3q28 and encodes the claudin protein which is found primarily in the kidneys, in the thick ascending limb (TAL) of the loop of Henle where it regulates the paracellular resorption of magnesium ions. The defects in the CLDN16 gene are a cause of primary hypomagnesemia (FHHNC) (OMIM # 248250; HOMG3), which is characterized by massive. The mutations in the gene encoding the claudin protein can result in the aforementioned renal disorder in this case, the disease phenotype is complicated by ocular involvement The mutations in CLDN16 and CLDN19 occur throughout the coding region and can affect proper folding, intracellular trafficking of the protein or its paracellular pore forming function [2]. The defects in the CLDN16 gene are a cause of primary hypomagnesemia (FHHNC), which is characterized by massive renal magnesium wasting, resulting in nephrocalcinosis and renal failure. The mutations occur throughout the gene’s coding region and can impact on intracellular trafficking of the protein or its paracellular pore forming function. Seven putative miRNA binding sites within the 3’-UTR region of CLDN16 were identified
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
