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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed August 2015

What is the official name of the PHKA2 gene?

The official name of this gene is “phosphorylase kinase, alpha 2 (liver).”

PHKA2 is the gene's official symbol. The PHKA2 gene is also known by other names, listed below.

What is the normal function of the PHKA2 gene?

The PHKA2 gene provides instructions for making one piece, the alpha subunit, of the phosphorylase b kinase enzyme. This enzyme is made up of 16 subunits, four each of the alpha, beta, gamma, and delta subunits. (Each subunit is produced from a different gene.) The alpha subunit helps regulate the activity of phosphorylase b kinase. This enzyme is found in various tissues, although it is most abundant in the liver and muscles. One version of the enzyme is found in liver cells and another in muscle cells. The alpha-2 subunit produced from the PHKA2 gene is part of the enzyme found in the liver.

Phosphorylase b kinase plays an important role in providing energy for cells. The main source of cellular energy is a simple sugar called glucose. Glucose is stored in muscle and liver cells in a form called glycogen. Glycogen can be broken down rapidly when glucose is needed, for instance to maintain normal levels of glucose in the blood between meals. Phosphorylase b kinase turns on (activates) another enzyme called glycogen phosphorylase b by converting it to the more active form, glycogen phosphorylase a. When active, this enzyme breaks down glycogen.

How are changes in the PHKA2 gene related to health conditions?

glycogen storage disease type IX - caused by mutations in the PHKA2 gene

At least 90 mutations in the PHKA2 gene are known to cause a form of glycogen storage disease type IX (GSD IX) called GSD IXa or X-linked liver glycogenosis (XLG). This is the most common form of GSD IX, accounting for approximately 75 percent of cases. GSD IXa affects liver function, and its characteristic features include an enlarged liver (hepatomegaly), slow growth, and periods of low blood sugar (hypoglycemia). These features usually improve over time. However, some affected individuals have a buildup of scar tissue (fibrosis) in the liver, which can rarely progress to irreversible liver disease (cirrhosis).

Mutations in the PHKA2 gene reduce the activity of phosphorylase b kinase in liver cells, although the mechanism is unknown. Reduction of this enzyme's function impairs glycogen breakdown. As a result, glycogen builds up in cells, and glucose is not available for energy. Glycogen accumulation in the liver leads to hepatomegaly and can damage the organ. The inability to break down glycogen for energy contributes to hypoglycemia and the other features of GSD IXa.

There are two subtypes of GSD IXa, known as XLG1 and XLG2, which are classified by the activity of phosphorylase b kinase in various tissues. In XLG1, the more common subtype, enzyme activity is decreased in the liver and in red blood cells. In contrast, in XLG2, the enzyme's activity appears low or normal in the liver and normal or high in red blood cells when measured by laboratory tests. The subtypes are indistinguishable based on symptoms.

Where is the PHKA2 gene located?

Cytogenetic Location: Xp22.2-p22.1

Molecular Location on the X chromosome: base pairs 18,892,298 to 18,984,362

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The PHKA2 gene is located on the short (p) arm of the X chromosome between positions 22.2 and 22.1.

The PHKA2 gene is located on the short (p) arm of the X chromosome between positions 22.2 and 22.1.

More precisely, the PHKA2 gene is located from base pair 18,892,298 to base pair 18,984,362 on the X chromosome.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about PHKA2?

You and your healthcare professional may find the following resources about PHKA2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the PHKA2 gene or gene products?

  • GSD9A
  • PHK
  • phosphorylase b kinase regulatory subunit alpha, liver isoform
  • phosphorylase kinase alpha L subunit
  • phosphorylase kinase alpha-subunit
  • PYK
  • PYKL
  • XLG

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding PHKA2?

breakdown ; cirrhosis ; enzyme ; fibrosis ; gene ; glucose ; glycogen ; hypoglycemia ; kinase ; muscle cells ; simple sugar ; subunit ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Brushia RJ, Walsh DA. Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure. Front Biosci. 1999 Sep 15;4:D618-41. Review. (
  • Burwinkel B, Amat L, Gray RG, Matsuo N, Muroya K, Narisawa K, Sokol RJ, Vilaseca MA, Kilimann MW. Variability of biochemical and clinical phenotype in X-linked liver glycogenosis with mutations in the phosphorylase kinase PHKA2 gene. Hum Genet. 1998 Apr;102(4):423-9. (
  • Burwinkel B, Shin YS, Bakker HD, Deutsch J, Lozano MJ, Maire I, Kilimann MW. Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis due to phosphorylase kinase deficiency with atypical activity in blood cells (XLG2). Hum Mol Genet. 1996 May;5(5):653-8. (
  • Hendrickx J, Lee P, Keating JP, Carton D, Sardharwalla IB, Tuchman M, Baussan C, Willems PJ. Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type I and II. Am J Hum Genet. 1999 Jun;64(6):1541-9. (
  • NCBI Gene (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: August 2015
Published: February 8, 2016