Early onset or syndromic epilepsy
Gene: MAST3
Comment on mode of pathogenicity: It would appear that MAST3 variants have a gain-of-function effect (PMID:34185323).Created: 7 May 2024, 12:15 p.m. | Last Modified: 7 May 2024, 12:15 p.m.
Panel Version: 5.9
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 7 May 2024, 12:14 p.m. | Last Modified: 7 May 2024, 12:14 p.m.
Panel Version: 5.8
MAST3 variants have been associated with Developmental and epileptic encephalopathy 108 (OMIM:620115). PMID:34185323 reports five de novo missense MAST3 variants in eleven unrelated individuals with developmental and epileptic encephalopathy, with a range of seizure types. These variants are within the serine-threonine kinases (STK) domain. PMID: 35095415 reports a further four de novo missense MAST3 variants, within the domain of unknown function (DUF). It would appear that the variants within the STK domain are associated with a neurodevelopmental disorder with a epilepsy phenotype, while variants within the DUF domain have a autistic spectrum disorder phenotype (PMID: 35095415)
Functional studies suggest that the MAST3 variants have a gain-of-function effect (PMID:34185323; 35095415).Created: 7 May 2024, 12:11 p.m. | Last Modified: 7 May 2024, 12:59 p.m.
Panel Version: 5.10
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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
Tag Q2_24_NHS_review tag was added to gene: MAST3.
Publications for gene: MAST3 were set to 34185323
Mode of pathogenicity for gene: MAST3 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: mast3 has been classified as Amber List (Moderate Evidence).
Tag Q2_24_promote_green tag was added to gene: MAST3. Tag Q2_24_MOI tag was added to gene: MAST3.
gene: MAST3 was added gene: MAST3 was added to Early onset or syndromic epilepsy. Sources: Literature Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MAST3 were set to 34185323 Mode of pathogenicity for gene: MAST3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: MAST3 was set to GREEN