Neuronal ceroid lipofuscinosis

Gene: CLCN6

Amber List (moderate evidence)

CLCN6 (chloride voltage-gated channel 6)
EnsemblGeneIds (GRCh38): ENSG00000011021
EnsemblGeneIds (GRCh37): ENSG00000011021
OMIM: 602726, Gene2Phenotype
CLCN6 is in 2 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least three de novo occurrances of a single variant reported.
Created: 17 Mar 2021, 6:31 p.m. | Last Modified: 17 Mar 2021, 6:31 p.m.
Panel Version: 1.23
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 17 Mar 2021, 6:27 p.m. | Last Modified: 17 Mar 2021, 6:27 p.m.
Panel Version: 1.23
Comment on phenotypes: There is no Mondo term for this phenotype at present
Created: 17 Mar 2021, 6:24 p.m. | Last Modified: 17 Mar 2021, 6:24 p.m.
Panel Version: 1.21

Zornitza Stark (Australian Genomics)

Green List (high evidence)

PMID 33217309: Three unrelated families reported with recurrent GOF de novo c.1658A>G (p.Tyr553Cys) and severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans.

Previously, monoallelic variants reported in 3 families with BPEI, but functional data/segregation not compelling.

Mouse knockout model has features of NCL.
Created: 9 Dec 2020, 8:08 a.m. | Last Modified: 9 Dec 2020, 8:08 a.m.
Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration; Benign partial epilepsy; febrile seizures; NCL

Publications

Emma Ashton (Great Ormond Street Hospital)

Red List (low evidence)

Mode of inheritance
Unknown

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • NHS GMS
  • London North GLH
Phenotypes
  • Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173
Tags
Q2_21_rating
OMIM
602726
Clinvar variants
Variants in CLCN6
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Mar 2021, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: CLCN6.

17 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: clcn6 has been classified as Amber List (Moderate Evidence).

17 Mar 2021, Gel status: 1

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: CLCN6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

17 Mar 2021, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: CLCN6 were changed from to Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173

17 Mar 2021, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116

9 Jul 2019, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: CLCN6 were set to

13 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ivone Leong (Genomics England Curator)

gene: CLCN6 was added gene: CLCN6 was added to Neuronal ceroid lipofuscinosis. Sources: London North GLH,NHS GMS,Expert Review Red Mode of inheritance for gene: CLCN6 was set to Unknown