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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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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description 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
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series Kuwait Journal of Science
spelling doaj-art-bfbdb4bfd79346abb28c4aa50bba25ec2025-08-20T02:10:28ZengElsevierKuwait Journal of Science2307-41082307-41162025-01-0152110034410.1016/j.kjs.2024.100344In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type XGlycogen 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 Authorshttps://www.sciencedirect.com/science/article/pii/S230741082400169X3pgframeshift mutationglycogen storage disease type xmolecular dockingmutation analysispgam2premature translation terminationprotein modelling
spellingShingle In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X
Kuwait Journal of Science
3pg
frameshift mutation
glycogen storage disease type x
molecular docking
mutation analysis
pgam2
premature translation termination
protein modelling
title In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X
title_full In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X
title_fullStr In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X
title_full_unstemmed In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X
title_short In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X
title_sort in silico analysis of point mutation c 687dupc p met230hisfs∗6 in pgam2 gene that causes glycogen storage disease gsd type x
topic 3pg
frameshift mutation
glycogen storage disease type x
molecular docking
mutation analysis
pgam2
premature translation termination
protein modelling
url https://www.sciencedirect.com/science/article/pii/S230741082400169X