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Fetal anomalies

Gene: CLCN5

Red List (low evidence)
CLCN5 (chloride voltage-gated channel 5)
EnsemblGeneIds (GRCh38): ENSG00000171365
EnsemblGeneIds (GRCh37): ENSG00000171365
OMIM: 300008, Gene2Phenotype
CLCN5 is in 10 panels

3 reviews

Elizabeth Scotchman (North Thames Genomic Laboratory Hub)

Red List (low evidence)

PMID 38267993: hemizygous pathogenic variant c.1942 C_>_T (p.R648*), first case of prenatal diagnosis for Dent disease type I with a nonsense pathogenic variant of the CLCN5 gene. However, the phenotypes of low-molecular-weight proteinuria or hypercalciuria were unable to be determined throughout the fetal period. Furthermore, the disease does not seem to cause any abnormality in the fetus that can be detected by ultrasound.
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.
Panel Version: 5.15

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Nephrolithiasis, type I, MIM#310468; Dent disease, MIM#300009; Hypophosphatemic rickets, MIM#300554

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Achchuthan Shanmugasundram (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.
Panel Version: 5.16
Comment on list classification: As reviewed by Sarah Graham, this gene has been rated red in this panel.
Created: 26 Jun 2024, 10:20 a.m. | Last Modified: 26 Jun 2024, 10:20 a.m.
Panel Version: 4.9
Created: 26 Jun 2024, 10:20 a.m.
Last Modified: 26 Jun 2024, 10:20 a.m.
Panel version: 5.16

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Red List (low evidence)

Loss-of-function variants associated with X-linked recessive renal tubular disorders. Maternally inherited hemizygous splice variant, c.934-1G>T, reported in 3 male fetuses with variable phenotypes across 3 studies from the same centre. Phenotypes in reported cases: polyhydramnios and large size for gestational age (Fu 2022 PMID: 36307859, case 229); growth restriction, polyhydramnios, pre-term birth at 31 weeks (Zhou 2023 PMID: 36495297, patient 5); microcephaly (Wang 2023 PMID: 37229200, patient 18). No definitive evidence that this variant is pathogenic. As all prenatal reports are of the same variant and from the same centre, concern that these may be incidental findings due to variant frequency in the local population (variant absent from gnomAD).
Sources: Literature
Created: 15 Jun 2024, 10:50 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Publications

Created: 15 Jun 2024, 10:50 a.m.

Panel version: 4.3

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • NHS GMS
  • Expert Review Red
Phenotypes
  • Dent disease 1, OMIM:300009
  • Hypophosphatemic rickets, OMIM:300554
  • Nephrolithiasis, type I, OMIM:310468
  • Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, OMIM:308990
OMIM
300008
Clinvar variants
Variants in CLCN5
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Feb 2025, Gel status: 1

Added New Source, Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to CLCN5. Publications for gene: CLCN5 were updated from 36307859; 36495297; 37229200 to 36495297; 38267993; 36307859; 37229200

26 Jun 2024, Gel status: 1

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: clcn5 has been classified as Red List (Low Evidence).

26 Jun 2024, Gel status: 1

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: clcn5 has been classified as Red List (Low Evidence).

25 Jun 2024, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: CLCN5 were changed from to Dent disease 1, OMIM:300009; Hypophosphatemic rickets, OMIM:300554; Nephrolithiasis, type I, OMIM:310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, OMIM:308990

15 Jun 2024, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

gene: CLCN5 was added gene: CLCN5 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: CLCN5 were set to 36307859; 36495297; 37229200 Review for gene: CLCN5 was set to RED