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  3. CLCN4
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Intellectual disability syndromic and non-syndromic

Gene: CLCN4

Green List (high evidence)
CLCN4 (chloride voltage-gated channel 4)
EnsemblGeneIds (GRCh38): ENSG00000073464
EnsemblGeneIds (GRCh37): ENSG00000073464
OMIM: 302910, Gene2Phenotype
CLCN4 is in 7 panels

1 review

Elizabeth Palmer (University of New South Wales)

Green List (high evidence)

epilepsy common in CLCN4 related disorder and can range from epileptic encephalopathy to well controlled seizures. Heterozygous females with de novo variants can be as severely affected as males: A555V variant is recurrent in females. Occasionally heterozygous females with an inherited variant can be severely affected by epilepsy and intellectual disability although typically are not or only mildly affected with mild learning difficulties and increased chance of mental health disorders.
NB in addition to the 16 families published we have over 40 additional families in our CLCN4 database. Pathogenic missense variants are rare, have supportive in silico pathogenicity scores and alter electrophysiological model in Xenopus oocytes. To date all loss of function variant are causal of a neurocognitive phenotype.
Created: 19 Dec 2019, 5:30 a.m. | Last Modified: 19 Dec 2019, 5:30 a.m.
Panel Version: 0.1429

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
intellectual disability; epilepsy; autistic features; mood disorders; cerebral white matter changes; progressive appendicular spasticity

Publications

Created: 19 Dec 2019, 5:30 a.m.
Last Modified: 19 Dec 2019, 5:30 a.m.
Panel version: 0.1429

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Genetic Health Queensland
Phenotypes
  • Raynaud-Claes syndrome, MIM#300114
  • intellectual disability
  • epilepsy
  • autistic features
  • mood disorders
  • cerebral white matter changes
  • progressive appendicular spasticity
OMIM
302910
Clinvar variants
Variants in CLCN4
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Dec 2019, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: clcn4 has been classified as Green List (High Evidence).

19 Dec 2019, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: CLCN4 were changed from to Raynaud-Claes syndrome, MIM#300114; intellectual disability; epilepsy; autistic features; mood disorders; cerebral white matter changes; progressive appendicular spasticity

19 Dec 2019, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: CLCN4 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

19 Dec 2019, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: CLCN4 were set to

22 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: CLCN4 was added gene: CLCN4 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: CLCN4 was set to Unknown