GYS1

GYS1 Full Name

glycogen synthase 1 (muscle)

GYS1 Introduction

GYS1, located on chromosome 19q13.3, encodes muscle glycogen synthase, a glycosyltransferase that catalyzes the rate-limiting elongation step of glycogen synthesis by transferring glucose residues from UDP-glucose onto the growing glycogen chain through α-1,4-glycosidic linkages. The enzyme is most abundantly expressed in skeletal and cardiac muscle, where it converts postprandial glucose into glycogen for local energy reserve. Its activity is tightly regulated by reversible phosphorylation: insulin-stimulated dephosphorylation activates the enzyme, while phosphorylation by GSK3, PKA, and AMPK inhibits it, allowing rapid switching between storage and mobilization according to hormonal and energetic state. Functionally, GYS1 determines the capacity of muscle to store glycogen and to sustain contractile activity. During exercise, glycogenolysis supplies the ATP required for sustained contraction, and the inability to replenish these stores compromises performance and recovery. Beyond substrate storage, GYS1 also contributes to whole-body glucose disposal, influencing glucose homeostasis and insulin sensitivity. Loss-of-function mutations in GYS1 abolish glycogen synthesis in muscle, forcing excess glucose into alternative metabolic fates and eliminating the principal local energy reserve available during exertion. Animal models confirm that GYS1-deficient muscle compensates through mitochondrial proliferation and oxidative remodeling.

Figure 1. Deletion of Gys1 suppresses burn-induced thermogenesis in WAT and mitigates fatty liver. (Source: Zhuo S, et al. 2025)

Clinically, recessive loss-of-function mutations in GYS1 cause muscle glycogen storage disease type 0 (GSD0B), a rare disorder characterized by exercise intolerance, muscle pain, weakness, and syncope following moderate exertion. The cardiac phenotype is the most consequential feature: absence of cardiac glycogen predisposes to hypertrophic cardiomyopathy, arrhythmia, long QT, and sudden cardiac death, often in childhood. A recently described adult-onset phenotype presents as a milder proximal myopathy without cardiomyopathy, broadening the recognized clinical spectrum. Diagnosis relies on enzymatic assay of muscle biopsy demonstrating marked glycogen depletion and reduced glycogen synthase activity, supported by sequence analysis of GYS1, underscoring the importance of considering GSD0B in unexplained myopathies.

Alternate Names for GYS1

GYS1; glycogen synthase 1 (muscle); GSY; GYS; glycogen [starch] synthase, muscle;

• 1. Zhuo S, et al. Blocking glycogen synthase 1 in white adipose tissue alleviates hypermetabolism following severe burn injury through inhibition of JAK2 by UDPG. Cell Rep. 2025 Dec 23;44(12):116577.
  2. Cameron JM, et al. Identification of a novel mutation in GYS1 (muscle-specific glycogen synthase) resulting in sudden cardiac death, that is diagnosable from skin fibroblasts. Mol Genet Metab. 2009 Dec;98(4):378-82.