Analysisofmissensesnpsin Humanlrp5 Gene By In Silicoapproach

Mrinmoyee Sengupta; Mitali Das

doi:10.48165/

Authors

Mrinmoyee Sengupta Laboratory of Molecular Cell Biology and Genetics, Department of Zoology, University of Gour Banga, Malda - 732 101 West Bengal (India)
Mitali Das Laboratory of Molecular Cell Biology and Genetics, Department of Zoology, University of Gour Banga, Malda - 732 101 West Bengal (India)

DOI:

https://doi.org/10.48165/

Keywords:

Bone diseases, 3D structural effect, functional effect, in silico, LRP5, missense SNPs analysis

Abstract

Low-density lipoprotein receptor-related protein 5 (LRP5) is a protein, encoded by the LRP5 gene in humans. LRP5, the key component of the LRP5/LRP6/ Frizzled co-receptor group is involved in canonical Wnt pathway, a regulator of bone metabolism. Mutations in LRP5 can lead to considerable changes in bone mass following bone diseases. Our study aimed to predict the effect of missense SNPs in human LRP5 gene by in silico methods using publicly available online software tools and database. We predicted the functional effects of mutations by using VEP, PROVEAN, SNPs & GO, and PANTHER, effects on the stability of the protein by I-Mutant 2.0 and on the 3-Dstructure of the protein by Project HOPE. We used GeneMANIA to predict the interaction of LRP5 with 20 other genes. Over all this is a comprehensive study provides all the available information about the clinically significant missense SNPs of LRP5 at a glance.

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Abdelraheem, N.E., Osman, M.M., Elgemaabi, O.M., Alla, A.A.F., Ismail, M.M., Osman, S.A. and Hassan, M.A. 2016. Computational Analysis of Deleterious Single Nucleotide Polymorphisms (SNPs) in Human MutS Homolog6 (MSH6) Gene. American Journal of Bioinformatics Research, 6(2): 56-97.

Ahn, V.E., Chu, M.L., Choi, H.J., Tran, D., Abo, A. and Weis, W.I. 2011. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Developmental Cell, 21(5): 862-873. Ding, Y., Xi, Y., Chen, T., Wang, J.Y., Tao, D.L., Wu, Z.L., Li, Y.P., Li, C., Zeng, R. and Li, L. 2008.

Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation. The Journal of Cell Biology, 182(5): 865-872.

Franz, M., Rodriguez, H., Lopes, C., Zuberi, K., Montojo, J., Bader, G.D. and Morris, Q. 2018. Gene MANIA update 2018. Nucleic Acids Research, 46(W1): W60-W64. [https://doi.org/10.1093/ nar/gky311].

Gong, Y., Vikkula, M., Boon, L., Liu, J., Beighton, P., Ramesar, R., Peltonen, L., Somer, H., Hirose, T., Dallapiccola, B., De Paepe, A., Swoboda, W., Zabel, B., Superti-Furga, A., Steinmann, B., Brunner, H.G., Jans, A., Boles, R.G., Adkins, W., van den Boogaard, M.J. and Warman, M.L. 1996. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13.American Journal of Human Genetics, 59(1): 146-151.

Guo, Y.F., Xiong, D.H., Shen, H., Zhao, L.J., Xiao, P., Guo, Y., Wang, W., Yang, T.L., Recker, R.R. and Deng, H.W. 2006. Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study. Journal of Medical Genetics, 43(10): 798-803.

Hey, P.J., Twells, R.C., Phillips, M.S., Yusuke Nakagawa, Brown, S.D., Kawaguchi, Y., Cox, R., Guochun Xie, Dugan, V., Hammond, H., Metzker, M.L., Todd, J.A. and Hess, J.F. 1998. Cloning of a novel member of the low-density lipoprotein receptor family. Gene, 216(1): 103-111.

Keats, B. and Sherman, S.L. 2013. Population genetips. pp. 1-12. In: Emery and Rimoin's Principles and Practice of Medical Genetics. Elsevier, [doi:10.1016/b978-0-12-383834-6.00015-x]. Laine, C.M., Chung, B.D., Susic, M., Prescott, T., Semler, O., Fiskerstrand, T., d'Eufemia, P., Castori, M., Pekkinen, M., Sochett, E. and Cole, W.G. 2011. Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). European Journal of Human Genetics, 19(8): 875-881.

Lara-Castillo, N. and Johnson, M.L. 2015. LRP receptor family member associated bone disease. Reviews in Endocrine and Metabolic Disorders, 16(2): 141-148.

Lim, S.W., Tan, K.J., Azuraidi, O. M., Sathiya, M., Lim, E. C., Lai, K.S., Yap, W.S. and Afizan, N.A.R.N.M. 2021. Functional and structural analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the MYB oncoproteins associated with human cancer. Scientific Reports, 11(1), 24206. [https://doi.org/10.1038/s41598-021-03624-x].

Liu, K., Tan, L.J., Wang, P., Chen, X.D., Zhu, L.H., Zeng, Q., Hu, Y. and Deng, H.W. 2017. Functional relevance for associations between osteoporosis and genetic variants. PLoS One, 12(4): e0174808. [https://doi.org/10.1371/journal.pone.0174808].

Manfredi, M., Savojardo, C., Martelli, P.L. and Casadio, R. 2022. E-SNPs & GO: Embedding of protein sequence and function improves the annotation of human pathogenic variants. Bioinformatics (Oxford, England), 38(23): 5168-5174.

Mao, W., Wordinger, R.J. and Clark, A.F. 2011. Functional analysis of disease-associated polymorphism LRP5.Q89R. Molecular Vision, 17: 894-902.

Martin, F.J., Amode, M.R., Aneja, A., Austine-Orimoloye, O., Azov, A. G., Barnes, I., Becker, A., Bennett, R., Berry, A., Bhurji, S.K., Boddu, S., Branco Lins, P.R., Brooks, L., Ramaraju, S.B., Charkhchi, M., Cockburn, A., Da Rin Fiorretto, L., Davidson, C. and Flicek, P. 2023. Ensembl 2023. Nucleic Acids Research, 51(D1): D933-D941. [https://doi.org/10.1093/nar/gkac958].

Mrinmoyee Sengupta and Mitali Das

Mi, H., Ebert, D., Muruganujan, A., Mills, C., Albou, L.P., Mushayamaha, T. and Thomas, P.D. 2021. PANTHER version 16: A revised family classification, tree-based classification tool, enhancer regions and extensive API. Nucleic Acids Research, 49(D1): D394-D403. [https://doi.org/10.1093/nar/gkaa1106].

Nakano, M., Yui, H., Kikugawa, S., Tokida, R., Sakai, N., Kondo, N., Endo, N., Haro, H., Shimodaira, H., Suzuki, T., Kato, H., Takahashi, J. and Nakamura, Y. 2021. Associations of LRP5 and MTHFR gene variants with osteoarthritis Prevalence in Elderly Women: A Japanese Cohort Survey Randomly Sampled from a Basic Resident Registry. Therapeutics and Clinical Risk Management, 17: 1065-1073.

NCI’s Dictionary of Genetics Terms [online] 2022. [https://www.cancer.gov/publications/ dictionaries/genetics-dictionary/def/single-nucleotide-polymorphism]. (Accessed 19 July 2022) Nimir, M., Abdelrahim, M., Abdelrahim, M., Abdalla, M., Ahmed, W.E., Abdullah, M. and Hamid, M. M.A. 2017. In silico analysis of single nucleotide polymorphisms (SNPs) in human FOXC2 gene. F1000Research, 6: 243. [https://doi.org/10.12688/f1000research.10937.2]. Norwitz, N.G., Mota, A.S., Misra, M. and Ackerman, K.E. 2019. LRP5, Bone Density, and Mechanical Stress: A Case Report and Literature Review. Frontiers in Endocrinology, 10: 184. [https://doi.org/10.3389/fendo.2019.00184].

Pekkinen, M., Grigelioniene, G., Akin, L., Shah, K., Karaer, K., Kurtoğlu, S., Ekbote, A., Aycan, Z., Sağsak, E., Danda, S., Åström, E. and Mäkitie, O. 2017. Novel mutations in the LRP5 gene in patients with Osteoporosis-pseudoglioma syndrome. American Journal of Medical Genetics. Part A, 173(12): 3132-3135.

Qin, L.J., Ding, D.X., Cui, L.L. and Huang, Q.Y. 2013. Expression and regulation of the SOST gene. Hereditas, 35(8): 939-947.

Sandell, L. and Sharp, N.P. 2022. Fitness effects of mutations: An assessment of PROVEAN predictions using mutation accumulation data. Genome Biology and Evolution, 14(1): evac004. [https://doi.org/10.1093/gbe/evac004].

Shastry B.S. 2009. SNPs: Impact on gene function and phenotype. In: Methods in Molecular Biology (ed. N.J. Clifton), 578: 3-22.[ https://doi.org/10.1007/978-1-60327-411-1_1]. Teng, S., Srivastava, A.K., Schwartz, C.E., Alexov, E. and Wang, L. 2010. Structural assessment of the effects of amino acid substitutions on protein stability and protein-protein interaction. International Journal of Computational Biology and Drug Design, 3(4): 334-349. Ueki, M., Takeshita, H., Utsunomiya, N., Chino, T., Oyama, N., Hasegawa, M., Kimura-Kataoka, K., Fujihara, J., Iida, R. and Yasuda, T. 2017. Survey of single-nucleotide polymorphisms in the gene encoding human deoxyribonuclease I-like 2 producing loss of function potentially implicated in the pathogenesis of parakeratosis. PloS One, 12(4): e0175083. [https://doi.org/10.1371/journal.pone.0175083].

Vaser, R., Adusumalli, S., Leng, S.N., Sikic, M. and Ng, P.C. 2016. SIFT missense predictions for genomes. Nature Protocols, 11(1): 1-9.

Venselaar, H., Te Beek, T.A., Kuipers, R.K., Hekkelman, M.L. and Vriend, G. 2010. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC bioinformatics, 11: 548. [https://doi.org/10.1186/1471-2105-11-548].

Wang, Q.F., Bi, H.S., Qin, Z.L., Wang, P., Nie, F.F. and Zhang, G.W. 2020. Associations of LRP5 gene with bone mineral density, bone turnover markers, and fractures in the elderly with osteoporosis. Frontiers in Endocrinology, 11: 571549. [https://doi.org/10.3389/fendo.2020.571549].

Williams, B.O., and Insogna, K.L. 2009. Where Wnts went: The exploding field of Lrp5 and Lrp6 signaling in bone. Journal of Bone and Mineral Research, 24(2): 171-178.

Xu, G.Y., Qiu, Y. and Mao, H.J. 2014. Common polymorphism in the LRP5 gene may increase the risk of bone fracture and osteoporosis. BioMed Research International, 2014: 290531. [https://doi.org/10.1155/2014/290531].

Analysisofmissensesnpsin Humanlrp5 Gene By In Silicoapproach

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Applied Biological Research