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DOI :10.26650/EurJBiol.2022.1164864   IUP :10.26650/EurJBiol.2022.1164864    Full Text (PDF)

In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database

Şeref Gül

Objective: A circadian rhythm in mammals controls the sleep-wake cycle, blood pressure, hormone secretion, metabolism and many other physiological processes. The circadian clock mechanism is regulated by four genes: Bmal1, Clock, Cry, and Per. Mutations in these regulatory genes are associated with sleep and mood disorders, obesity, and cancer. Several PER2 and CRY2 SNPs are associated with advanced sleep phase syndrome. It is, therefore, critical to understand the effect of clock genes’ SNPs on the circadian clock. In this study, we determined “pathogenic” BMAL1 and CLOCK SNPs in the Ensembl database for biochemical characterization.

Materials and Methods: BMAL1 and CLOCK SNPs in the Ensemble database were filtered out for only missense mutations. Among the missense mutations, pathogenic ones were determined according to SIFT, PolyPhen, and CADD scores, REVEL, MetalR, Mutation Assessor, I-Mutant, PROVEAN, and FireDock programs. BMAL1 and CLOCK SNPs were visualized by using PyMol.

Results: Thousands of BMAL1 and CLOCK missense SNP mutations were reported in the Ensembl database. After the classification of those SNPs according to their SIFT, PolyPhen, and CADD pathogenicity, twelve SNPs for each protein remained as pathogenic. A further analysis with all in silico tools revealed that BMAL1 SNPs causing Ala154Val, Arg166Gln, and Val440Gly mutations; and CLOCK SNPs causing Gly120Val, Asp119Val, Gly120Ser, Ala117Val, and Cys371Gly mutations were predicted as the most “pathogenic” ones.

Conclusion: Overall, by using in silico tools, we provided a starting point for experimental studies for determining the effect of pathogenic BMAL1 and CLOCK SNPs on the circadian clock mechanism.

Keywords: Circadian clock, Ensembl, BMAL1, CLOCK, SNP

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APA

Gül, Ş. (2022). In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database. European Journal of Biology, 81(2), 125-135. https://doi.org/10.26650/EurJBiol.2022.1164864


AMA

Gül Ş. In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database. European Journal of Biology. 2022;81(2):125-135. https://doi.org/10.26650/EurJBiol.2022.1164864


ABNT

Gül, Ş. In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database. European Journal of Biology, [Publisher Location], v. 81, n. 2, p. 125-135, 2022.


Chicago: Author-Date Style

Gül, Şeref,. 2022. “In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database.” European Journal of Biology 81, no. 2: 125-135. https://doi.org/10.26650/EurJBiol.2022.1164864


Chicago: Humanities Style

Gül, Şeref,. “In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database.” European Journal of Biology 81, no. 2 (Nov. 2024): 125-135. https://doi.org/10.26650/EurJBiol.2022.1164864


Harvard: Australian Style

Gül, Ş 2022, 'In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database', European Journal of Biology, vol. 81, no. 2, pp. 125-135, viewed 22 Nov. 2024, https://doi.org/10.26650/EurJBiol.2022.1164864


Harvard: Author-Date Style

Gül, Ş. (2022) ‘In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database’, European Journal of Biology, 81(2), pp. 125-135. https://doi.org/10.26650/EurJBiol.2022.1164864 (22 Nov. 2024).


MLA

Gül, Şeref,. “In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database.” European Journal of Biology, vol. 81, no. 2, 2022, pp. 125-135. [Database Container], https://doi.org/10.26650/EurJBiol.2022.1164864


Vancouver

Gül Ş. In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database. European Journal of Biology [Internet]. 22 Nov. 2024 [cited 22 Nov. 2024];81(2):125-135. Available from: https://doi.org/10.26650/EurJBiol.2022.1164864 doi: 10.26650/EurJBiol.2022.1164864


ISNAD

Gül, Şeref. “In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database”. European Journal of Biology 81/2 (Nov. 2024): 125-135. https://doi.org/10.26650/EurJBiol.2022.1164864



TIMELINE


Submitted21.08.2022
Accepted20.10.2022
Published Online23.11.2022

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