Chloride channel 5
The gene codes a chloride channel. Mutations cause Dent disease.
Epidemiology
The frequency of CLCN5 mutations in general population is not known. We find mutations in this gene throughout the world. In Japan 70% of children with low molecular weight proteinuria carry mutation of this gene.
Gene Structure
The gene CLCN5 responsible for Dent disease type 1 is the voltage-gated chloride channel (CLCK2 or CLC5). The gene is located on the X chromosome and therefore is inherited depending on sex. The exact locus is (Xp11.22.) The gene with a size of about 25 kb consists of 12 exons, 11 are translated.
Expression
The gene is expressed in renal proximal tubule cells. Expression is highest below the brush border in a region densely packed with endocytotic vesicles. Colocalization with the H(+)-ATPase and with internalized proteins suggests its function in reabsorbtion of filtered proteins. In intercalated cells of the collecting duct it again localizes to apical intracellular vesicles and colocalizes with the proton.
Phenotype
Typical are various renal tubular disorders which result in kidney stone formation (nephrolithiasis), hypophosphatemic rickets, low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis. Sometimes additionally hematuria, glycosuria, aminoaciduria, impaired urinary concentrating ability, and mild decrease in creatinine clearance can be seen.
Test Strategy
Unclear cases of proteinuria, hypercalciuria, and hypophosphatemia. Family counseling in case of familiar hypophosphatemic rickets.
Interpretation
The clinical importance is in clarifying the reason of proteinuria. Maybe preventing a child from renal biopsy.
Genetests:
Related Diseases:
Urolithiasis
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Cystinuria
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SLC3A1
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SLC7A9
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Dicarboxylic aminoaciduria
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SLC1A1
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Dihydroxyadenin urolithiasis
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APRT
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Nephrocalcinosis
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Bartter syndrome
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Antenatal Bartter syndrome type 1
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SLC12A1
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Antenatal Bartter syndrome type 2
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KCNJ1
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Classic Bartter syndrome
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CLCNKB
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Hypercalciuric hypocalcemia 1
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CASR
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Hypercalciuric hypocalcemia 2
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GNA11
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Infantile Bartter syndrome with deafness type 4
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BSND
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CLCNKA
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CLCNKB
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Transient antenatal Bartter syndrome
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MAGED2
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Dent disease
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CLCN5
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OCRL
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Hereditary Rickets
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Hypophosphatasia
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Adult hypophosphatasia
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ALPL
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Childhood hypophosphatasia
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ALPL
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Infantile hypophosphatasia
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ALPL
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Odontohypophosphatasia
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ALPL
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Hypophosphatemic bone and kindney disease
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Disorders of the renal phosphate transporters
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Hypophosphatemic rickets with hypercalciuria
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SLC34A3
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Idiopathic basal ganglia calcification 1
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SLC20A2
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Nephrolithiasis/osteoporosis, hypophosphatemic, 1
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SLC34A1
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Nephrolithiasis/osteoporosis, hypophosphatemic, 2
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SLC9A3R1
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FGF23-induced hypophosphatemic rickets
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Autosomal dominant hypophosphatemic rickets
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FGF23
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Autosomal recessive hypophosphatemic rickets type 1
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DMP1
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Autosomal recessive hypophosphatemic rickets type 2
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ENPP1
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X-linked dominant hypophosphatemic rickets
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PHEX
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Fanconi-type hypophosphatemic rickets
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Nephrolithiasis/osteoporosis, hypophosphatemic, 1
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SLC34A1
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X-linked recessive hypophosphatemic rickets
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CLCN5
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OCRL
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Hypophosphatemic rickets with hyperparathyroidism
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KL
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Osteoglophonic dysplasia
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FGFR1
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Raine syndrome
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FAM20C
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X-linked dominant hypophosphatemic rickets
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PHEX
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Vitamin D hydroxylation-deficient rickets type 1A
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CYP27B1
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Vitamin D hydroxylation-deficient rickets type 1B
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CYP2R1
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Vitamin D-dependent rickets, type 2A
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VDR
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Vitamin D-dependent rickets, type 2B
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RXRA
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Hyperoxaluria
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Hyperoxaluria type 1
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AGXT
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Hyperoxaluria type 2
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GRHPR
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Hyperoxaluria type 3
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HOGA1
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Hypomagnesemia with hypercalciuria and nephrocalcinosis
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CLDN16
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Hypomagnesemia with hypercalciuria and nephrocalcinosis with ocular involvement
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CLDN19
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Infantile hypercalcemia
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CYP24A1
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Lowe disease
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OCRL
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Renal tubular acidosis
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Combined renal tubular acidosis 3 with osteopetrosis 3
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CA2
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Distal renal tubular acidosis (autosomal dominant)
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SLC4A1
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Distal renal tubular acidosis (autosomal recessive)
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ATP6V0A4
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Distal renal tubular acidosis with deafness (autosomal recessive)
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ATP6V1B1
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Proximal renal tubular acidosis
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SLC4A4
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Renal tubular acidosis with arthrogryposis
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Arthrogryposis, renal dysfunction, and cholestasis 1
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VPS33B
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Arthrogryposis, renal dysfunction, and cholestasis 2
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VIPAS39
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Williams-Beuren syndrome
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ELN
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Nephrolithiasis diarrhea syndrome
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SLC26A6
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Susceptibility to nephrolithiasis
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ALPL
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CASR
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SLC26A1
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TRPV5
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ZNF365
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Uric acid nephropathy
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Hyperuricemic nephropathy
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Hyperuricemic nephropathy, familial juvenile 1
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UMOD
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Hyperuricemic nephropathy, familial juvenile 2
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REN
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Kelley-Seegmiller syndrome
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HPRT1
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Lesch-Nyhan syndrome
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HPRT1
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Renal Hypouricemia
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SLC22A12
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SLC2A9
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References:
1. |
None (2004) The molecular basis of kidney stones.
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2. |
None (2000) Pathogenesis of Dent's disease and related syndromes of X-linked nephrolithiasis.
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3. |
Orphanet article
Orphanet ID 119453
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4. |
NCBI article
NCBI 1184
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5. |
OMIM.ORG article
Omim 300008
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6. |
Wikipedia article
Wikipedia EN (CLCN5)
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Update: Aug. 14, 2020