CLCN5

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]

Chloride Voltage-Gated Channel 5

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.

Chloride transport Source: InterPro
Endocytosis Source: Ensembl
Excretion Source: ProtInc
Ion transmembrane transport Source: Reactome

Hypophosphatemic rickets, X-linked recessive (XLRHR):
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.
Nephrolithiasis 2 (NPHL2):
An X-linked recessive 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. Nephrolithiasis type 2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia.
Nephrolithiasis 1 (NPHL1):
An X-linked recessive 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. Nephrolithiasis type 1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia.
Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN):
An X-linked 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. LMWPHN is a slowly progressive disorder. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure.

Cytoplasmic: 1-124
Helical: 125-162
Helical: 208-231
Helical: 240-247
Helical: 256-275
Helical: 281-300
Helical: 312-324
Helical: 328-336
Helical: 348-366
Helical: 389-415
Helical: 422-442
Helical: 498-518
Helical: 523-542
Helical: 570-584
Loop between two helices: 585-587
Helical: 588-599
Loop between two helices: 600-604
Helical: 605-622
Cytoplasmic: 623-816

Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation.