Skeletal muscle channelopathy

Gene: ATP1A2

Green List (high evidence)

ATP1A2 (ATPase Na+/K+ transporting subunit alpha 2)
EnsemblGeneIds (GRCh38): ENSG00000018625
EnsemblGeneIds (GRCh37): ENSG00000018625
OMIM: 182340, Gene2Phenotype
ATP1A2 is in 19 panels

4 reviews

Eleanor Williams (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Leaving rating as Green but with a recommendation for review by GMS evaluation group as to suitability for this panel. There is only one case reported associated with a skeletal muscle phenotype.
Created: 8 Jun 2021, 5:30 p.m. | Last Modified: 20 Jul 2021, 1:55 p.m.
Panel Version: 1.31
Associated with Alternating hemiplegia of childhood 1 #104290 and Migraine, familial basilar/Migraine, familial hemiplegic, 2 #602481 in OMIM which are both CNS disorders.

PMID: 30423015 - Castaneda et al 2018 - report a 9 yo Brazilian boy with hypokalaemic periodic paralysis and CNS involvement, including seizures. He presented with episodes of flaccid muscle paralysis. A heterozygous de novo missense mutation (c.G2336A, p.S779N) in the ATP1A2 gene was identified using focussed exome sequencing. Electrophysiological studies in Xenopus oocytes of the p.S779N mutant pump showed an anomalous inward leak current and altered turnover rates. The authors postulate that this provides a mechanistic explanation for the periodic paralysis and CNS symptoms, respectively.

Other papers mentioned by James Polke
PMID: 15286158 - Bassi et al 2004 - report about alternating hemiplegia of childhood.
PMID: 18056581 - de Vries et al 2007 - report patients with hemiplegic migraine

A Pubmed search does not find any further cases of hypokalaemic periodic paralysis associated with ATP1A2
Created: 8 Jun 2021, 5:27 p.m. | Last Modified: 8 Jun 2021, 5:27 p.m.
Panel Version: 1.21

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

Phenotypes
hypokalaemic periodic paralysis MONDO:0008223

Publications

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Variants in this gene are predominantly linked to brain phenotypes such as alternating hemiplegia. Single report plus functional data linking to hypokalaemic periodic paralysis.
Created: 20 Aug 2020, 8:42 a.m. | Last Modified: 20 Aug 2020, 8:42 a.m.
Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypokalaemic periodic paralysis

Publications

Louise Daugherty (Genomics England Curator)

I don't know

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:57 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

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

Phenotypes
Hypokalaemic periodic paralysis; Alternating hemiplegia of childhood 1, 104290; Migraine, familial hemiplegic, 2, 602481

Publications

  • Castaneda et al 2018 Brain 141, 3308-3318 PMID: 30423015. Bassi et al 2004 J Med Genet 41, 621-8 PMID: 15286158. de Vries et al 2007 Neurology 69, 2170-6 PMID: 18056581

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

History Filter Activity

20 Jul 2021, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: ATP1A2.

9 Jun 2021, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_phenotype tag was added to gene: ATP1A2.

8 Jun 2021, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: atp1a2 has been classified as Green List (High Evidence).

8 Jun 2021, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: ATP1A2.

8 Jun 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ATP1A2 were changed from Migraine, familial hemiplegic, 2, 602481; Alternating hemiplegia of childhood 1, 104290; Hypokalaemic periodic paralysis to hypokalaemic periodic paralysis MONDO:0008223

8 Jun 2021, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ATP1A2 were set to 30423015; 15286158; 18056581

25 Oct 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene ATP1A2 were changed from to 30423015; 15286158; 18056581

25 Oct 2019, Gel status: 3

Set mode of inheritance, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene ATP1A2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Migraine, familial hemiplegic, 2, 602481; Alternating hemiplegia of childhood 1, 104290; Hypokalaemic periodic paralysis for gene: ATP1A2

28 Apr 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to ATP1A2. Rating Changed from Red List (low evidence) to Green List (high evidence)

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ATP1A2.

28 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: ATP1A2 was added gene: ATP1A2 was added to Myotonia congenita. Sources: London North GLH Mode of inheritance for gene: ATP1A2 was set to