This report describes glycogen storage disease IXa. The human gene implicated is PHKA2, hich encodes the alpha-2 subunit of hepatic phosphorylase kinase. There is one high-scoring fly ortholog, Dmel\Phka, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human gene PHKA2 has not been introduced into flies.
Null Dmel\Phka mutants exhibit larger and denser larval fat deposits and greater bouyancy than do control larvae. Null mutants exhibit elevated mitochondrial function around larval neuromuscular junctions.
[updated Aug. 2026 by FlyBase; FBrf0222196]
[GLYCOGEN STORAGE DISEASE IXa1; GSD9A1](https://omim.org/entry/306000)
[PHOSPHORYLASE KINASE, LIVER, ALPHA-2 SUBUNIT; PHKA2](https://omim.org/entry/300798)
Glycogen storage disease type IX (GSD9) is a metabolic disorder resulting from a deficiency of hepatic phosphorylase kinase, a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes: alpha (PHKA2), beta (PHKB), gamma (PHKG2), and delta (CALM1). Mutations within the PHKA2, PHKB, and PHKG2 genes result in GSD9A, GSD9B (MIM:261750), and GSD9C (MIM:613027), respectively. GSD IXa is an X-linked recessive disorder, whereas the others are autosomal recessive.
GSD IXa has been further divided into types IXa1 (GSD9A1), with no PHK activity in liver or erythrocytes, and IXa2 (GSD9A2), with no PHK in liver, but normal activity in erythrocytes. The clinical presentation of both subtypes is the same, and both are caused by mutations in the PHKA2 gene. However, mutations that result in IXa2 are either missense or small in-frame deletions or insertions enabling residual enzyme expression in erythrocytes (Keating et al., 1985, pubmed:3859203; Hendrickx et al., 1994, pubmed:7959740; Beauchamp et al., 2007, pubmed:17689125).
Glycogen storage disease IXa is one of the mildest of the glycogenoses of man. Clinical symptoms include hepatomegaly, growth retardation, elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting hyperketosis These clinical and biochemical abnormalities gradually disappear with age, and most adult patients are asymptomatic (Schimke et al., 1973, pubmed:4518931; Willems et al., 1990, pubmed:2303074). [from MIM:306000; 2026.08.05]
Glycogen storage disease type IXa (GSD9A1) and type IXa2 (GSD9A2) are caused by mutation in the PHKA2 gene, which encodes the alpha-2 subunit of hepatic phosphorylase kinase, on chromosome Xp22. [from MIM:306000; 2026.08.05]
The PHKA2 gene encodes the alpha subunit of hepatic phosphorylase kinase. Hepatic phosphorylase kinase is a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes: alpha (PHKA2), beta (PHKB, MIM:172490), gamma (PHKG2, (MIM:172471)), and delta. The delta subunit can be encoded by 3 different genes (CALM1, MIM:114180; CALM2, MIM:114182; or CALM3, MIM:114183). The PHKA1 (MIM:311870) and PHKG1 (MIM:172470) genes encode the alpha and gamma subunits, respectively, of muscle phosphorylase kinase; the beta subunit is the same in both isoforms. 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, which encodes calmodulin, mediates the dependence of the enzyme on calcium concentration (Beauchamp et al., 2007, pubmed:17689125). [from MIM:300798; 2026.08.05]
One to one (1 human to 1 Drosophila); PHKA2 has one high-scoring Drosophila ortholog, Phka.
High-scoring ortholog of human PHKA1 and PHKA2 (1 Drosophila to 2 human).
