PHKA2

Chr XXLR

phosphorylase kinase regulatory subunit alpha 2

Also known as: GSD9A, PHK, PYK, PYKL, XLG, XLG2

NCBI Gene: 5256 ENSG00000044446 UniProt: P46019 OMIM: 300798

The PHKA2 gene encodes the hepatic alpha subunit of phosphorylase kinase, a regulatory enzyme in glycogen metabolism where the alpha subunit controls enzyme activity through phosphorylation while the gamma subunit contains the catalytic site. Mutations cause glycogen storage disease types IXa1 and IXa2 (X-linked liver glycogenosis) through loss of phosphorylase kinase regulation, leading to impaired glycogen breakdown in the liver. This follows X-linked recessive inheritance, primarily affecting males.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, which are encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9A, also known as X-linked liver glycogenosis. Alternatively spliced transcript variants have been reported, but the full-length nature of these variants has not been determined.[provided by RefSeq, Feb 2010]

OMIM ResearchGenerating clinical summary…

XLRLOEUF 0.372 OMIM phenotypes

Clinical Summary— PHKA2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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