Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
31 03 2022
31 03 2022
Historique:
received:
02
11
2021
accepted:
08
03
2022
entrez:
1
4
2022
pubmed:
2
4
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Hereditary glutathione reductase deficiency, caused by mutations of the GSR gene, is an autosomal recessive disorder characterized by decreased glutathione disulfide (GSSG) reduction activity and increased thermal instability. This study implemented computational analysis to screen the most likely mutation that might be associated with hereditary glutathione reductase deficiency and other diseases. Using ten online computational tools, the study revealed four nsSNPs among the 17 nsSNPs identified as most deleterious and disease associated. Structural analyses and evolutionary confirmation study of native and mutant GSR proteins using the HOPE project and ConSruf. HOPE revealed more flexibility in the native GSR structure than in the mutant structure. The mutation in GSR might be responsible for changes in the structural conformation and function of the GSR protein and might also play a significant role in inducing hereditary glutathione reductase deficiency. LD and haplotype studies of the gene revealed that the identified variations rs2978663 and rs8190955 may be responsible for obstructive heart defects (OHDs) and hereditary anemia, respectively. These interethnic differences in the frequencies of SNPs and haplotypes might help explain the unpredictability that has been reported in association studies and can contribute to predicting the pharmacokinetics and pharmacodynamics of drugs that make use of GSR.
Identifiants
pubmed: 35361806
doi: 10.1038/s41598-022-09295-6
pii: 10.1038/s41598-022-09295-6
pmc: PMC8971378
doi:
Substances chimiques
Glutathione Reductase
EC 1.8.1.7
Glutathione
GAN16C9B8O
Glutathione Disulfide
ULW86O013H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5474Informations de copyright
© 2022. The Author(s).
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