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DOI :10.26650/EurJBiol.2022.1164864   IUP :10.26650/EurJBiol.2022.1164864    Tam Metin (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.

Anahtar Kelimeler: Circadian clockEnsemblBMAL1CLOCKSNP

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Gül, Ş. (2022). In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database. European Journal of Biology, 81(2), 125-135.


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


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.

Chicago: Humanities Style

Gül, Şeref,. In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database.” European Journal of Biology 81, no. 2 (Jul. 2024): 125-135.

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 21 Jul. 2024,

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. (21 Jul. 2024).


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],


Gül Ş. In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database. European Journal of Biology [Internet]. 21 Jul. 2024 [cited 21 Jul. 2024];81(2):125-135. Available from: doi: 10.26650/EurJBiol.2022.1164864


Gül, Şeref. In Silico Analysis of BMAL1 and CLOCK SNPs in the Ensembl Database”. European Journal of Biology 81/2 (Jul. 2024): 125-135.


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