ATP8A2

Chr 13

ATPase phospholipid transporting 8A2

Also known as: ATP, ATPIB, CAMRQ4, IB, ML-1

NCBI Gene: 51761 ENSG00000132932 UniProt: Q9NTI2

ATP8A2 encodes a P4-ATPase flippase that translocates phospholipids (particularly phosphatidylserine) from the outer to inner membrane leaflet to maintain membrane asymmetry and support vesicle trafficking in neuronal cells. Mutations cause cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants and the protein is required for normal visual and auditory function as well as photoreceptor and inner ear spiral ganglion cell survival.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4

Clinical highlights

Gene-disease validity (ClinGen)

cerebellar ataxia, intellectual disability, and dysequilibrium · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.60

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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