NM_152296.5(ATP1A3):c.3035ACT[3] (p.Tyr1013dup) AND Dystonia 12

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 1, 2009
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000148335.4

Allele description [Variation Report for NM_152296.5(ATP1A3):c.3035ACT[3] (p.Tyr1013dup)]

NM_152296.5(ATP1A3):c.3035ACT[3] (p.Tyr1013dup)

Gene:

ATP1A3:ATPase Na+/K+ transporting subunit alpha 3 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_152296.5(ATP1A3):c.3035ACT[3] (p.Tyr1013dup)

Other names:

3-BP DUP, 3191TAC

HGVS:

NC_000019.10:g.41966941TAG[3]
NG_008015.1:g.32287ACT[3]
NM_001256213.2:c.3068ACT[3]
NM_001256214.2:c.3074ACT[3]
NM_152296.5:c.3035ACT[3]MANE SELECT
NP_001243142.1:p.Tyr1024dup
NP_001243143.1:p.Tyr1026dup
NP_689509.1:p.Tyr1013dup
LRG_1186t1:c.3035ACT[3]
LRG_1186:g.32287ACT[3]
LRG_1186p1:p.Tyr1013dup
NC_000019.9:g.42471093TAG[3]

Links:

OMIM: 182350.0008; dbSNP: rs397515382

NCBI 1000 Genomes Browser:

rs397515382

Molecular consequence:

NM_001256213.2:c.3068ACT[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001256214.2:c.3074ACT[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_152296.5:c.3035ACT[3] - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:: Dystonia 12 (DYT12)
Synonyms:: DYT-ATP1A3; Rapid-Onset Dystonia-Parkinsonism
Identifiers:: MONDO: MONDO:0007496; MedGen: C1868681; Orphanet: 71517; OMIM: 128235

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034026	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2009)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000034026

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2009)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism.

Blanco-Arias P, Einholm AP, Mamsa H, Concheiro C, Gutiérrez-de-Terán H, Romero J, Toustrup-Jensen MS, Carracedo A, Jen JC, Vilsen B, Sobrido MJ.

Hum Mol Genet. 2009 Jul 1;18(13):2370-7. doi: 10.1093/hmg/ddp170. Epub 2009 Apr 7.

PubMed [citation]

PMID:: 19351654

Details of each submission

From OMIM, SCV000034026.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 16-year-old female with dystonia-12 (DYT12; 128235), Blanco-Arias et al. (2009) reported a de novo heterozygous 3-bp duplication (3191dupTAC) in exon 23 of the ATP1A3 gene, resulting in duplication of tyr1013, the C-terminal amino acid of the protein before the stop codon. The mutation was not found in either parent, her brother, or in 218 control individuals. HeLa cells expressing the mutant protein showed decreased survival in response to ouabain challenge, but no defect was detected in protein expression or plasma membrane targeting. Functional analysis demonstrated a drastic 40- to 50-fold reduction in Na+ affinity in the mutant. Blanco-Arias et al. (2009) suggested a crucial role for the C terminus of the alpha-subunit in the function of the Na+/K(+)-ATPase and emphasized a key impact of Na+ affinity in the pathophysiology of DYT12.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 23, 2022

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