Human Gene CLCN5 (ENST00000376091.8) from GENCODE V44
Description: Homo sapiens chloride voltage-gated channel 5 (CLCN5), transcript variant 2, mRNA. (from RefSeq NM_001127898) RefSeq Summary (NM_001127898): This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]. Gencode Transcript: ENST00000376091.8 Gencode Gene: ENSG00000171365.17 Transcript (Including UTRs) Position: hg38 chrX:49,922,596-50,099,230 Size: 176,635 Total Exon Count: 15 Strand: + Coding Region Position: hg38 chrX:49,925,299-50,092,219 Size: 166,921 Coding Exon Count: 13
ID:CLCN5_HUMAN DESCRIPTION: RecName: Full=H(+)/Cl(-) exchange transporter 5; AltName: Full=Chloride channel protein 5; Short=ClC-5; AltName: Full=Chloride transporter ClC-5; FUNCTION: Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function. SUBUNIT: Interacts with NEDD4 and NEDD4L. SUBCELLULAR LOCATION: Golgi apparatus membrane; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Kidney. Moderately expressed in aortic vascular smooth muscle and endothelial cells, and at a slightly higher level in the coronary vascular smooth muscle. PTM: Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation. DISEASE: Defects in CLCN5 are a cause of hypophosphatemic rickets, X-linked recessive (XLRHR) [MIM:300554]. XLRHR is a renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only. DISEASE: Defects in CLCN5 are the cause of nephrolithiasis type 2 (NPHL2) [MIM:300009]; also known as Dent disease 1. NPHL2 is an X- linked recessive renal disease belonging to the 'Dent disease complex'. NPHL2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia. DISEASE: Defects in CLCN5 are the cause of nephrolithiasis type 1 (NPHL1) [MIM:310468]; also designated XRN. NPHL1 is an X-linked recessive renal disease belonging to the 'Dent disease complex'. NPHL1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia. DISEASE: Defects in CLCN5 are the cause of low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) [MIM:308990]. LMWPHN is an X-linked renal disease belonging to the 'Dent disease complex'. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure. MISCELLANEOUS: The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels. SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-5/CLCN5 subfamily. SIMILARITY: Contains 2 CBS domains. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CLCN5";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P51795
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
