Early onset or syndromic epilepsy
Gene: MAST3

MAST3 (microtubule associated serine/threonine kinase 3)
EnsemblGeneIds (GRCh38): ENSG00000099308
EnsemblGeneIds (GRCh37): ENSG00000099308
OMIM: 612258, Gene2Phenotype
MAST3 is in 3 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

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: 26 Sep 2024, 10:58 a.m. | Last Modified: 26 Sep 2024, 10:58 a.m.

Panel Version: 6.6

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

Created: 26 Sep 2024, 10:58 a.m.
Last Modified: 26 Sep 2024, 10:58 a.m.
Panel version: 6.6

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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

34185323

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 7 May 2024, 12:11 p.m.
Last Modified: 7 May 2024, 12:59 p.m.
Panel version: 5.7

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green
NHS GMS
Literature

OMIM

612258

Clinvar variants

Variants in MAST3

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

26 Sep 2024, Gel status: 3

Removed Tag, Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_24_promote_green was removed from gene: MAST3. Tag Q2_24_MOI was removed from gene: MAST3. Tag Q2_24_NHS_review was removed from gene: MAST3.

26 Sep 2024, Gel status: 3

Added New Source, Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to MAST3. Source Expert Review Green was added to MAST3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

7 May 2024, Gel status: 2