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  3. RALGAPA1
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Early onset or syndromic epilepsy

Gene: RALGAPA1

Green List (high evidence)
RALGAPA1 (Ral GTPase activating protein catalytic alpha subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000174373
EnsemblGeneIds (GRCh37): ENSG00000174373
OMIM: 608884, Gene2Phenotype
RALGAPA1 is in 3 panels

4 reviews

Helen Lord (Oxford Medical Genetics Laboratories)

I don't know

Wagner et al 2020 - bialleleic RALGAPA1 variants in 4 unrelated individuals with profound neurodevelopmental disability, muscular hypotonia, feeding abnormalities, recurrent fever episodes and infantile spasms. Dysplasia of corpus callosum and characteristic facial features appear to be unifying features. 3/4 had infantile spasms between the ages of 8 and 12 months. RALGAA1 was absent in the fibroblasts derived from 2 affected individuals siggesting a LOF effect of these variants. Consequently RalA activity was increased in these cell lines, which is in keeping with the idea that RALGAPA1 deficiency causes a constitutive activation of RalA. Additionally, levels of RALGAPB, a scaffolding subunit of the RalGAP complex, were dramatically reduced, indicating a dysfunctional RalGAP complex.
Created: 31 Jan 2021, 8:15 p.m. | Last Modified: 31 Jan 2021, 8:15 p.m.
Panel Version: 2.281

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 31 Jan 2021, 8:15 p.m.
Last Modified: 31 Jan 2021, 8:15 p.m.
Panel version: 2.281

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Created: 20 Oct 2020, 4:06 p.m. | Last Modified: 20 Oct 2020, 4:06 p.m.
Panel Version: 2.199
Created: 20 Oct 2020, 4:06 p.m.
Last Modified: 20 Oct 2020, 4:06 p.m.
Panel version: 2.199

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.
Panel Version: 2.491
Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for RALGAPA1-related neurodevelopmental disorder. At least 5 variants reported in at least 4 unrelated cases.
Created: 23 Mar 2020, 2:32 p.m. | Last Modified: 23 Mar 2020, 2:32 p.m.
Panel Version: 2.11
Comment on phenotypes: Intellectual disability;hypotonia;infantile spasms
Created: 23 Mar 2020, 2:21 p.m. | Last Modified: 23 Mar 2020, 2:21 p.m.
Panel Version: 2.10
Created: 23 Mar 2020, 2:21 p.m.
Last Modified: 23 Mar 2020, 2:21 p.m.
Panel version: 2.491

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four unrelated individuals reported.
Sources: Expert list
Created: 2 Feb 2020, 11:04 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; hypotonia; infantile spasms.

Publications

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

Created: 2 Feb 2020, 11:04 a.m.

Panel version: 2.0

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • .Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation 618797
OMIM
608884
Clinvar variants
Variants in RALGAPA1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Mar 2022, Gel status: 3

Removed Tag

Sarah Leigh (Genomics England Curator)

Tag for-review was removed from gene: RALGAPA1.

3 Mar 2022, Gel status: 3

Added New Source, Status Update

Sarah Leigh (Genomics England Curator)

Source Expert Review Green was added to RALGAPA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

20 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ralgapa1 has been classified as Amber List (Moderate Evidence).

20 Oct 2020, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: RALGAPA1.

23 Mar 2020, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: ralgapa1 has been classified as Green List (High Evidence).

23 Mar 2020, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: RALGAPA1 were changed from Intellectual disability; hypotonia; infantile spasms. to .Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation 618797

2 Feb 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: RALGAPA1 was added gene: RALGAPA1 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: RALGAPA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RALGAPA1 were set to 32004447 Phenotypes for gene: RALGAPA1 were set to Intellectual disability; hypotonia; infantile spasms. Review for gene: RALGAPA1 was set to GREEN gene: RALGAPA1 was marked as current diagnostic