Adult onset neurodegenerative disorder
Gene: NEK1
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
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
Variants in this GENE are reported as part of current diagnostic practice
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 AmberCreated: 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
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
Variants in this GENE are reported as part of current diagnostic practice
Tag Q1_23_promote_green was removed from gene: NEK1.
Source Expert Review Green was added to NEK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q1_23_promote_green tag was added to gene: NEK1.
Gene: nek1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NEK1 were changed from {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892 to {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892; amyotrophic lateral sclerosis, susceptibility to, 24, MONDO:0054750
Publications for gene: NEK1 were set to 29650794; 26945885; 30093141
Phenotypes for gene: NEK1 were changed from Amyotrophic lateral sclerosis, susceptibility to, 24; 617892 to {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892
Mode of inheritance for gene NEK1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Amyotrophic lateral sclerosis, susceptibility to, 24; 617892 for gene: NEK1 Publications for gene NEK1 were changed from to 29650794; 26945885; 30093141
Source NHS GMS was added to NEK1.
Source Yorkshire and North East GLH was added to NEK1.
gene: NEK1 was added gene: NEK1 was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Amber Mode of inheritance for gene: NEK1 was set to