This report describes Dent disease 1, one of several related forms of hereditary renal tubular disorders caused by mutations in the CLCN5 gene, which encodes chloride voltage-gated channel 5, a member of the ClC family of chloride ion channels and ion transporters. Other related disorders include X-linked recessive nephrolithiasis (MIM:310468), X-linked recessive hypophosphatemic rickets (MIM:300554), and low molecular weight proteinuria (MIM:308990); there is disagreement as to whether these are separate, or phenotypic variants of a single disease. There is one high-scoring fly ortholog, Dmel\ClC-c, for which multiple genetic reagents, including loss of function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Wild-type human CLCN5 has been introduced into flies, but has not been analyzed in the context of disease, nor been used to rescue Dmel\ClC-c alleles.
Dmel\ClC-c protein is observed to localized to the apical, but not basolateral, membrane of Malpighian tubules. RNAi-mediated knockdown of Dmel\ClC-c in Malpighian tubule principal cells results in an increase in precipitation of calcium oxalate, and formation of calcium oxalate crystals, in Malpighian tubules.
[updated May 2024 by FlyBase; FBrf0222196]
[DENT DISEASE 1; DENT1](https://omim.org/entry/300009)
[CHLORIDE CHANNEL 5; CLCN5](https://omim.org/entry/300008)
The term 'X-linked hypercalciuric nephrolithiasis' comprises several related forms of hereditary renal tubular disorders caused by mutations in the CLCN5 gene, including Dent disease, X-linked recessive nephrolithiasis (MIM:310468), X-linked recessive hypophosphatemic rickets (MIM:300554), and low molecular weight proteinuria (MIM:308990). Although these disorders are allelic and are all characterized by progressive proximal renal tubulopathy with hypercalciuria, low molecular weight proteinuria, and nephrocalcinosis, they vary in degree of severity and were originally reported as separate disorders. Some have considered these disorders as phenotypic variants of a single disease, referred to as the 'Dent disease complex' (Scheinman, 1998, pubmed:9452994; Gambaro et al., 2004, pubmed:15558518). [from MIM:300009; 2024.05.22]
Dent disease 1 is caused by mutation in the CLCN5 gene on chromosome Xp11. [from MIM:300009; 2024.05.22]]
CLCN5 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. [provided by RefSeq, Jan 2013]
The CLCN5 gene encodes a voltage-gated chloride ion channel that belongs to a distinct branch of the chloride channel (CLC) family, which also includes CLCN3 and CLCN4 (Fisher et al., 1995, pubmed:8575751). [from MIM:300008; 2243.05.22]
Many to one (many human to 1 Drosophila); CLCN5 has one high-scoring Drosophila ortholog, ClC-c.
High-scoring ortholog of human CLCN3, CLCN4, CLCN5, moderate scoring ortholog of human CLCNKA, CLCNKB, CLCNK6 (1 Drosophila to many human).
