Adult onset neurodegenerative disorder

Gene: NEK1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 4:47 p.m. | Last Modified: 10 Oct 2023, 4:47 p.m.

Panel Version: 4.37

Associated with Amyotrophic lateral sclerosis, susceptibility to, 24 (OMIM:617892), but not associated with a relevant phenotype in Gen2Phen. At least 12 NEK1 variants have been reported in amyotrophic lateral sclerosis cases (PMID: 30093141; 31768050; 26945885; 27455347), together with supportive functional studies (PMID: 2992911).
ClinGen Definitive gene - disease classification (29/04/2022): https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_bb4f311c-df33-4d9e-8ac6-731b43b93615-2022-04-29T192526.542Z?page=1&size=25&search=

Created: 2 Mar 2023, 2:43 p.m. | Last Modified: 14 Mar 2023, 2:36 p.m.

Panel Version: 3.58

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 2 Mar 2023, 1:41 p.m. | Last Modified: 2 Mar 2023, 1:41 p.m.

Panel Version: 3.57

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

Exome-wide significant burden of heterozygous loss-of-function identified in ALS case-control studies that is replicated in both familial and simplex cohorts. Segregation of a PTV reported in 2 affected first-degree relatives in a single family. A loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons.

Created: 28 Sep 2020, 3:23 a.m. | Last Modified: 28 Sep 2020, 3:23 a.m.

Panel Version: 2.16

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic lateral sclerosis, susceptibility to, 24 MIM#617892

Publications

• 31768050
• 26945885
• 27455347
• 29929116

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

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber

Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.

Panel Version: 1.106

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

I don't know

Significant number of individuals reported with variants in gene. No familial studies found.

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Amyotrophic lateral sclerosis, susceptibility to, 24, 617892

Publications

• 26945885
• 30093141
• 29650794

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