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ATP8A2
ATPase phospholipid transporting 8A2
The ATP8A2 gene provides instructions for making a protein involved in transporting phospholipids, playing a vital role in membrane asymmetry and various cellular processes, particularly within the nervous system. ATP8A2, or ATPase phospholipid transporting 8A2, is a gene that encodes a protein crucial for maintaining the specific arrangement of phospholipids in cell membranes.
ATP8A2 is located on the long (q) arm of chromosome 13, at band 13q12.13. Arm ratio per GRCh38 - banding schematic.
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Overview
The ATP8A2 gene encodes the ATPase phospholipid transporting 8A2 protein, which belongs to a family of P4-ATPases. These proteins are responsible for moving specific phospholipids from one leaflet of a cell membrane to another, a process known as 'flipping'. This action helps to maintain membrane asymmetry, which is essential for many cellular functions, including signal transduction, vesicle formation, and cell division.
What the gene does
The protein produced from the ATP8A2 gene acts as a flippase, specifically transporting phosphoserine and phosphatidylethanolamine across cell membranes. This directed movement is critical for establishing and maintaining the distinct lipid composition of the inner and outer membrane leaflets. In the nervous system, the ATP8A2 protein contributes to the proper functioning of neurons by supporting membrane integrity and efficient neurotransmission. Its activity is particularly important in brain development and the maintenance of cognitive functions, with disruption potentially impacting neuronal signalling pathways and overall neurological health.
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Chromosome location
The ATP8A2 gene is situated on chromosome 13, specifically at position 13q12.13. This location indicates its precise address within the human genome, helping researchers to identify and study its role in health and disease.
Protein structure
The ATP8A2 protein consists of 1188 amino acids. Its structural composition includes a Disordered region, spanning amino acids 1162-1188. This disordered region may play a role in protein-protein interactions or regulatory mechanisms, though its precise function requires further characterisation.
Key variants
Variations within the ATP8A2 gene can influence the structure and function of the encoded protein. These genetic changes can range from single base-pair alterations to larger deletions or insertions. Different types of variants may have varying impacts on protein activity, potentially leading to a spectrum of clinical manifestations.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1756C>T | p.Arg586Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.1761dup | p.Arg588fs | Pathogenic/Likely pathogenic | ★★☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.1782+2T>C | - | Pathogenic | ★★☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.2212-1G>C | - | Pathogenic | ★★☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.3272+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.77-2A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
g.(?_26043095)_(26273503_?)del | - | Pathogenic | ★☆☆☆ | not provided |
c.3316dup | p.Glu1106fs | Pathogenic | ★☆☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.649C>T | p.Gln217Ter | Pathogenic | ★☆☆☆ | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4 |
c.812T>G | p.Leu271Ter | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Changes in the ATP8A2 gene are associated with inherited neurological disorders, reflecting its critical role in brain development and function. Conditions linked to ATP8A2 typically involve impairments in neurological processes, underscoring the gene's importance in maintaining central nervous system health.
No disease links recorded for this gene in our reference set.
UK clinical status
The ATP8A2 gene is included in several NHS Genomic Medicine Service national test panels within the UK. It is on the Ataxia and cerebellar anomalies - narrow panel and is categorised as green, indicating it has strong evidence for gene-disease association. It is also found on the Intellectual disability panel, which is also green (R29), signifying its relevance in specific intellectual disability presentations.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the ATP8A2 gene?
The ATP8A2 gene provides instructions for making a protein that acts as a flippase. This protein transports specific phospholipids across cell membranes, which is essential for maintaining membrane asymmetry and supporting various cellular functions, particularly within the nervous system.
Why is membrane asymmetry important?
Membrane asymmetry is crucial because it ensures that the inner and outer leaflets of cell membranes have different lipid compositions. This distinct arrangement is vital for processes such as cell signalling, vesicle trafficking, and maintaining the structural integrity and function of cells.
What types of conditions are associated with ATP8A2 gene variants?
Variants in the ATP8A2 gene are associated with inherited neurological disorders. These conditions often involve issues with brain development and function, reflecting the gene's important role in the nervous system.