Authors :
Yamini Sri Sekar; Kuralayanapalya Puttahonnappa Suresh; Uma Bharathi Indrabalan; Madhumitha B.; Swati Rani; Sharanagouda S. Patil; Azhahianambi Palavesam; Nagendra Nath Barman
Volume/Issue :
Volume 8 - 2023, Issue 11 - November
Google Scholar :
https://tinyurl.com/ymcc747f
Scribd :
https://tinyurl.com/2hsrs7uh
DOI :
https://doi.org/10.5281/zenodo.10319617
Abstract :
The EGR-1 gene encodes the EGR-1 protein
in humans, featuring three zinc finger domains crucial
for DNA binding and transcriptional regulation. While
comprehensive investigations into the EGR-1 gene have
occurred, a research gap persists in the systematic
analysis of single nucleotide polymorphisms (SNPs)
associated with this gene. This study aimed to fill this
void by identifying and compiling a systematic collection
of damaging non-synonymous SNPs (nsSNPs) within the
EGR-1 gene, seeking a better understanding of
mutational changes. From 2,712 SNPs in the dbSNP
database, 455 non-synonymous missense substitutions
were selected for analysis. These substitutions were then
used to identify dominant variants, assess potential
consequences, and conduct mutation analyses based on
subPSEC scores. Gibbs free energy changes affected by
dominant substitutions were examined, distinguishing
between neutral and effect variants, and evaluated
functional and phenotypic effects.Further analysis
involved modeling substitutions to assess their structural
impact on the EGR-1 protein, elucidating disturbances
in interaction with closely related genes and pinpointing
changes in binding affinity and hydrogen bonds. Our
analysis identified five nsSNPs as the most hazardous
substitutions, with rs201213506 (H334N) recognized as
the most detrimental mutation in the DNA binding
region of the EGR-1 gene. This investigation effectively
revealed the significant impact of the H334N mutation
on the gene's regulatory capabilities. Further exploration
and understanding of these genetic variations could lead
to the identification of innovative therapeutic markers
for various inherited human diseases.
Keywords :
Early growth response(EGR)-1 gene; nsSNP; Computational analysis; protein-protein interaction; Docking.
The EGR-1 gene encodes the EGR-1 protein
in humans, featuring three zinc finger domains crucial
for DNA binding and transcriptional regulation. While
comprehensive investigations into the EGR-1 gene have
occurred, a research gap persists in the systematic
analysis of single nucleotide polymorphisms (SNPs)
associated with this gene. This study aimed to fill this
void by identifying and compiling a systematic collection
of damaging non-synonymous SNPs (nsSNPs) within the
EGR-1 gene, seeking a better understanding of
mutational changes. From 2,712 SNPs in the dbSNP
database, 455 non-synonymous missense substitutions
were selected for analysis. These substitutions were then
used to identify dominant variants, assess potential
consequences, and conduct mutation analyses based on
subPSEC scores. Gibbs free energy changes affected by
dominant substitutions were examined, distinguishing
between neutral and effect variants, and evaluated
functional and phenotypic effects.Further analysis
involved modeling substitutions to assess their structural
impact on the EGR-1 protein, elucidating disturbances
in interaction with closely related genes and pinpointing
changes in binding affinity and hydrogen bonds. Our
analysis identified five nsSNPs as the most hazardous
substitutions, with rs201213506 (H334N) recognized as
the most detrimental mutation in the DNA binding
region of the EGR-1 gene. This investigation effectively
revealed the significant impact of the H334N mutation
on the gene's regulatory capabilities. Further exploration
and understanding of these genetic variations could lead
to the identification of innovative therapeutic markers
for various inherited human diseases.
Keywords :
Early growth response(EGR)-1 gene; nsSNP; Computational analysis; protein-protein interaction; Docking.
