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Intellectual disability

Gene: ATP1A3

Amber List (moderate evidence)

ATP1A3 (ATPase Na+/K+ transporting subunit alpha 3)
EnsemblGeneIds (GRCh38): ENSG00000105409
EnsemblGeneIds (GRCh37): ENSG00000105409
OMIM: 182350, Gene2Phenotype
ATP1A3 is in 17 panels

5 reviews

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: Changed from Green to Amber after external clinical comment and internal clinical review. Of the three phenotypes in OMIM that are associated: CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) / Alternating hemiplegia of childhood / Dystonia 12, intellectual disability is only a reported feature in Alternating hemiplegia of childhood. However, all three phenotypes are caused by monoallelic variants and therefore through tiering they will not be readily distinguishable. The other phenotypes include a later onset neurological decline. Overall it was recommended the gene is downgraded to Amber, as although there is ID reported, there is no precedent for presentation with global developmental delay alone. Therefore we would expect this phenotype to be picked up via the brain channelopathy panel (relevant to intermittent / alternating hemiplegia) or the dystonia panel in view of the dystonic component. The gain from inclusion on the ID panel is probably smaller than the risk of incidental information for the majority of the ID cohort.
Created: 8 Aug 2018, 12:21 p.m.
Comment on phenotypes: Removed RAPID-ONSET DYSTONIA-PARKINSONISM, as it is only the Alternating Hemiplegia of Childhood (AHC) disorder that includes an ID phenotype
Created: 8 Aug 2018, 12:09 p.m.
Comment on publications: added publications to support evidence for Alternating hemiplegia of childhood 2 (that includes ID)
Created: 1 Aug 2018, 1:54 p.m.
Due to a Amber external review from external reviewer, and looking at the info again in the literature I am not sure why this gene was rated as Green based on the evidence for Dystonia-12, since it seems Alternating hemiplegia of childhood phenotype that includes intellectual disability that is relevant to this panel
Created: 1 Aug 2018, 1:35 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four additional individuals with dystonia, dysmorphism, encephalopathy with developmental delay, brain MRI abnormalities always including cerebellar hypoplasia, no hemiplegia, and neonatal onset. All had de novo missense variants. All are described to have global developmental delay, hence supporting upgrade in rating on this panel.
Created: 8 Sep 2020, 10:59 p.m. | Last Modified: 8 Sep 2020, 10:59 p.m.
Panel Version: 3.295
Definitely a green gene, but does it really cause intellectual disability?
Created: 14 Jun 2018, 9:29 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Alternating hemiplegia of childhood 2, MIM#614820; Neurodevelopmental disorder

Publications

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

Caroline Wright (Sanger)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
RAPID-ONSET DYSTONIA-PARKINSONISM

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_movement_disorder_list . Main mutation mechanism : All missense/in frame
Created: 27 Jul 2017, 5:08 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; manju_list; GEL_ID_green_20160217; neuro_20160418_strict; All missense/in frame. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:02 p.m.

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

Publications

  • 25529582
  • Personal communication with NIHRBRRD BRIDGE SPEED

Mode of pathogenicity
Other

Lu Raymond (university of cambridge )

I don't know

History Filter Activity

8 Aug 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: atp1a3 has been classified as Amber List (Moderate Evidence).

8 Aug 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ATP1A3 were set to Alternating Hemiplegia of Childhood (AHC), intellectual disability

1 Aug 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ATP1A3 were set to 22842232; 29396171; 29291920; 22842232; 28969699

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

3 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

3 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

ATP1A3 was added to Intellectual disabilitypanel. Sources: Expert Review Amber

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

ATP1A3 was created by ellenmcdonagh