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CLCN5 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- CLCN5 (HGNC:2023) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- chloride voltage-gated channel 5
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- NPHL2, NPHL1
- Alias symbols
- DENTS, XLRH, hClC-K2, hCIC-K2, CLC5, XRN, ClC-5
- %HI
- 13.07(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.99(Read more about gnomAD pLI score)
- LOEUF
- 0.28(Read more about gnomAD LOEUF score)
- Cytoband
- Xp11.23
- Genomic Coordinates
-
GRCh37/hg19: chrX:49687206-49863887 NCBI Ensembl UCSC GRCh38/hg38: chrX:49922596-50099230 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001127898.4 ENST00000376091.8 (Read more about MANE Select)
- Function
- Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons (PubMed:20466723). Important for normal acidification of the endosome lumen. May play an important role in renal tubular function. 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 (Proba... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- Dent disease type 1 Monarch
-
PUBMED:
15086899
32 unrelated males with a clinical diagnosis of Dent's disease underwent sequencing of CLCN5. Sixteen mutations were found in 19/32 individuals with 10 missense, 4 nonsense, and 2 frameshift mutations described.
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PUBMED:
22083641
In this review by Lourdel et al. (2012), 148 previously reported mutations in CLCN5 associated with Dent's disease were summarized. Of the 148 mutations reported, 36% were nonsense mutations, 30% missense mutations, 18% deletion mutations, 7% splice site mutations, and 6% insertional mutations. These mutations are divided into 3 categories depending on their effect on protein function. Functional studies and animal models are also summarized.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
