GYG2

GYG2 Full Name

glycogenin 2

GYG2 Introduction

GYG2, located on chromosome Xp22.33, encodes glycogenin-2, a glycosyltransferase belonging to family 8 that functions as an initiator of glycogen synthesis. Glycogenin proteins self-glucosylate an internal tyrosine residue using UDP-glucose, generating the short oligosaccharide primer required by glycogen synthase to begin elongation. GYG2 is expressed most prominently in liver, heart, pancreas, and certain neural tissues, partially overlapping with the more ubiquitous GYG1. Unlike GYG1, however, recent structural and cellular work demonstrates that GYG2 displays only minimal autoglycosylation activity and instead acts as a suppressor of glycogen formation, coordinating with GYG1 to modulate glycogen synthase activity in a cell-type-dependent manner. Mechanistically, GYG1 preferentially associates with the active, dephosphorylated form of glycogen synthase under high-glucose conditions to drive glycogen assembly, whereas GYG2 predominantly binds the phosphorylated, inactive form of the enzyme during both synthesis and breakdown. This dynamic interplay ensures proper glycogen particle size and tissue-specific regulation. Disruption of either glycogenin disturbs the homeostatic balance between glycogenesis and glycogenolysis, with downstream effects on glucose metabolic pathways. The two glycogenins therefore function as coordinated regulators of glycogen assembly, breakdown, and structural diversity across tissues, rather than simply redundant primers.

Figure 1. Physiological relevance of dynamic regulation of GYG1 and GYG2 and their interactions with GS in glycogen metabolism. (Source: Weng TH, et al. 2025)

The disease associations of GYG2 are still being delineated. Unlike GYG1, whose mutations cause glycogen storage disease type XV with muscle and cardiac involvement, GYG2 has proven unexpectedly dispensable for liver glycogen synthesis and glucagon-stimulated glucose release, as deletion carriers show preserved hepatic glycogen on biopsy. A hemizygous GYG2 missense variant (p.W222S) has been reported in two male siblings with Leigh-like neurodegenerative features, suggesting a possible link to mitochondrial-related encephalopathy. Additionally, GYG2 has emerged as a mitochondria-related aging biomarker in subcutaneous adipose tissue, hinting at broader metabolic relevance in diabetes and non-alcoholic fatty liver disease that warrants further investigation.

Alternate Names for GYG2

GYG2; glycogenin 2; GN2; GN-2; glycogenin-2; glycogenin glucosyltransferase;

• 1. Weng TH, et al. Human glycogenins maintain glucose homeostasis by regulating glycogen metabolism. Nat Commun. 2025 Jul 16;16(1):6556.
  2. Irgens HU, et al. Glycogenin-2 is dispensable for liver glycogen synthesis and glucagon-stimulated glucose release. J Clin Endocrinol Metab. 2015 May;100(5):E767-75.