ATP2B1

Chr 12

ATPase plasma membrane Ca2+ transporting 1

Also known as: MRD66, PMCA1, PMCA1kb

NCBI Gene: 490 ENSG00000070961 UniProt: P20020

The ATP2B1 protein is a plasma membrane calcium ATPase that removes calcium ions from cells to maintain intracellular calcium homeostasis and regulate blood pressure through vascular smooth muscle function. Mutations cause autosomal dominant intellectual developmental disorder with onset typically in early development. This gene is extremely intolerant to loss-of-function variants (pLI >0.99), indicating that functional copies are essential for normal neurodevelopment.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 1. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 66

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.08

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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