Neuronal ceroid lipofuscinosis
Gene: CLCN6EnsemblGeneIds (GRCh38): ENSG00000011021
EnsemblGeneIds (GRCh37): ENSG00000011021
OMIM: 602726, Gene2Phenotype
CLCN6 is in 5 panels
4 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 11:30 a.m. | Last Modified: 1 Feb 2023, 11:30 a.m.
Panel Version: 1.27
Sarah Leigh (Genomics England Curator)
Comment on mode of pathogenicity: PMID 33217309 reports gain of function associated with CLCN6 variants.Created: 8 Jan 2024, 2:54 p.m. | Last Modified: 8 Jan 2024, 2:54 p.m.
Panel Version: 2.5
PMIDs: 16950870 & 21107136 report the characterization of CLCN6 deficient mouse model, which display some features of neuronal ceroid lipofuscinosis. PMID: 16950870 identifies two heterozygous CLCN6 variants (p.V580M, p.T628R) in 2/75 patients with late-onset neuronal ceroid lipofuscinosis, however, the authors concluded that there was insufficient evidence for these variants being responsible for the phenotype in the patients.Created: 27 Jun 2023, 11:53 a.m. | Last Modified: 27 Jun 2023, 11:53 a.m.
Panel Version: 2.2
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 presentCreated: 17 Mar 2021, 6:24 p.m. | Last Modified: 17 Mar 2021, 6:24 p.m.
Panel Version: 1.21
Publications
Zornitza Stark (Australian Genomics)
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)
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 Green
- NHS GMS
- London North GLH
- Phenotypes
-
- Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173
- OMIM
- 602726
- Clinvar variants
- Variants in CLCN6
- Penetrance
- None
- Publications
- Mode of Pathogenicity
- Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
- Panels with this gene
History Filter Activity
Set mode of pathogenicity
Sarah Leigh (Genomics England Curator)Mode of pathogenicity for gene: CLCN6 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Set mode of pathogenicity
Sarah Leigh (Genomics England Curator)Mode of pathogenicity for gene: CLCN6 was changed from to None
Set publications
Sarah Leigh (Genomics England Curator)Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116; 21107136; 33217309
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_21_rating was removed from gene: CLCN6.
Added New Source, Status Update
Achchuthan Shanmugasundram (Genomics England Curator)Source Expert Review Green was added to CLCN6. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Added Tag
Sarah Leigh (Genomics England Curator)Tag Q2_21_rating tag was added to gene: CLCN6.
Entity classified by Genomics England curator
Sarah Leigh (Genomics England Curator)Gene: clcn6 has been classified as Amber List (Moderate Evidence).
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
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
Set publications
Sarah Leigh (Genomics England Curator)Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116
Set publications
Sarah Leigh (Genomics England Curator)Publications for gene: CLCN6 were set to
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