Renal tubulopathies

Gene: ATP1A1

Green List (high evidence)

ATP1A1 (ATPase Na+/K+ transporting subunit alpha 1)
EnsemblGeneIds (GRCh38): ENSG00000163399
EnsemblGeneIds (GRCh37): ENSG00000163399
OMIM: 182310, Gene2Phenotype
ATP1A1 is in 8 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting red to green as there are 3 cases plus some functional data.
Created: 4 Sep 2019, 3:43 p.m. | Last Modified: 4 Sep 2019, 3:43 p.m.
Panel Version: 1.90
Associated with Hypomagnesemia, seizures, and mental retardation 2 (#618314) in OMIM.

PMID: 30388404 - Schlingmann et al 2018 - describe 3 unrelated infants who are from non-consanguineous families and who presented with a disease phenotype consisting of generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Whole-exome sequencing and conventional Sanger sequencing identified heterozygous de novo mutations in ATP1A1 (p.Leu302Arg, p.Gly303Arg, p.Met859Arg). Functional studies show the critical role of the α1 subunit of Na+, K+-ATPase for the maintenance of ionic gradients, the generation of resting membrane potential, and the termination of neuronal activity in the central nervous system
Created: 29 Aug 2019, 4:07 p.m. | Last Modified: 29 Aug 2019, 4:07 p.m.
Panel Version: 1.82
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: ATP1A1; Suggested initial gene rating: green; Evidence for inclusion: Schlingmann et al 2018 Am J Hum Genet 103 (5) 808-816. PMID: 30388404, 3 families, all de novo;Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided
Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, MIM 618036

Publications

  • Schlingmann et al 2018 Am J Hum Genet 103 (5) 808-816. PMID: 30388404

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Hypomagnesemia, seizures, and mental retardation 2 618314
  • Charcot-Marie-Tooth disease, axonal, type 2DD, 618036
OMIM
182310
Clinvar variants
Variants in ATP1A1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

4 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: atp1a1 has been classified as Green List (High Evidence).

4 Sep 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ATP1A1 were changed from Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, 618036 to Hypomagnesemia, seizures, and mental retardation 2 618314; Charcot-Marie-Tooth disease, axonal, type 2DD, 618036

4 Sep 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: ATP1A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

18 Jun 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ATP1A1 were changed from to Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, 618036

18 Jun 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ATP1A1 were set to

3 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: ATP1A1 was added gene: ATP1A1 was added to Renal tubulopathies. Sources: NHS GMS Mode of inheritance for gene: ATP1A1 was set to