PRKAB2

Chr 1

protein kinase AMP-activated non-catalytic subunit beta 2

NCBI Gene: 5565 ENSG00000131791 UniProt: O43741 OMIM: 602741

The protein serves as a non-catalytic regulatory subunit of AMP-activated protein kinase (AMPK), an energy sensor that monitors cellular energy status and regulates metabolic pathways by phosphorylating key enzymes involved in fatty acid and cholesterol biosynthesis. Mutations cause Wolff-Parkinson-White syndrome with intellectual disability and other abnormalities, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.485), indicating that complete protein loss is poorly tolerated.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · UDDisputedevidence questions this relationship

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.48

LOEUF

Mechanism· predicted

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GeneReview available — PRKAB2

Authoritative clinical overview · Recommended first read