Disease relevance of PHKB

• Mutations in three different genes of phosphorylase kinase (Phk) subunits, PHKA2, PHKB and PHKG2, can give rise to glycogen storage disease of the liver [1].

High impact information on PHKB

• Several different autosomally inherited forms of PHK deficiency for which the PHKB could be a candidate gene have been described in humans and rats [2].
• Assignment of human genes for phosphorylase kinase subunits alpha (PHKA) to Xq12-q13 and beta (PHKB) to 16q12-q13 [2].
• In contrast, the beta subunit gene (PHKB) was found to be autosomal and was mapped to chromosome 16, region q12-q13 on the proximal long arm [2].
• Autosomal glycogenosis of liver and muscle due to phosphorylase kinase deficiency is caused by mutations in the phosphorylase kinase beta subunit (PHKB) [3].
• Although these severe translation-disrupting mutations occur in constitutively expressed sequences of the only known beta subunit gene of phosphorylase kinase, PHKB, they are associated with a surprisingly mild clinical phenotype, affecting virtually only the liver, and relatively high residual enzyme activity of approximately 10% [3].

Biological context of PHKB

• Plaque hybridization at reduced stringency led to the isolation of two processed pseudogenes, PHKBP1 and PHKBP2, but of no other PHKB-related sequences [4].
• This is the first missense mutation identified in PHKB, as opposed to nine translation-terminating mutations described to date [5].
• Our results localize PHKA to the X chromosome at the proximal end of the long arm, near the centromere, and PHKB to the same location on chromosome 5 [6].

Anatomical context of PHKB

• Phosphorylase-kinase-deficient liver glycogenosis with an unusual biochemical phenotype in blood cells associated with a missense mutation in the beta subunit gene (PHKB) [5].

Analytical, diagnostic and therapeutic context of PHKB

• To identify such mutations, the complete PHKB coding sequence was amplified by RT-PCR of RNA isolated from blood samples of patients and analyzed by direct sequencing of PCR products [3].
• The chromosomal locations of the rabbit genes for the alpha and beta subunits of phosphorylase kinase (PHKA and PHKB) were determined by in situ hybridization using rabbit cDNA probes [6].

References