In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X

Glycogen storage disease (GSD) type X is an autosomal recessive disorder that affects skeletal muscles and is caused by PGAM-2 (Phosphoglycerate Mutase-2) enzyme deficiency. This deficiency is due to a mutation in the PGAM-2 gene at chromosome number 7p13. A novel insertion mutation (c.687dupC) was...

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Bibliographic Details
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Kuwait Journal of Science
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Online Access:https://www.sciencedirect.com/science/article/pii/S230741082400169X
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Summary:Glycogen storage disease (GSD) type X is an autosomal recessive disorder that affects skeletal muscles and is caused by PGAM-2 (Phosphoglycerate Mutase-2) enzyme deficiency. This deficiency is due to a mutation in the PGAM-2 gene at chromosome number 7p13. A novel insertion mutation (c.687dupC) was reported recently in the Pakistani population. This study aimed to computationally study the effect of that mutation at the molecular level. Several in silico approaches were employed to understand the molecular mechanism behind PGAM2 enzyme deficiency. Modeling the wild-type and mutant PGAM2 protein revealed an absence of an alpha helix from the c-terminus. Binding site analysis showed the absence of a critical residue, Lysine-100, from the mutant. Moreover, changes in the binding affinities, intramolecular interactions, and intermolecular interactions were also observed. © 2024 The Authors
ISSN:2307-4108
2307-4116