Affiliation:
1. Bursa Uludag University
Abstract
Abstract
G-protein-couple receptor family C group 5 member A (GPRC5A) encodes a transmembrane protein and is induced by retinoic acid. Dysfunctional GPRC5A was reported to activate numerous signal transduction cascades and its tumor suppressor role was emphasized especially in lung cancer in recent studies. Furthermore, various cancers, including colorectal cancer, breast cancer, and pancreatic cancer, have also been associated with GPRC5A dysregulation. In current study, we analysed the functional consequences of single nucleotide variants (SNVs) in the human GPRC5A gene using in-silico tools. We classified 76 missense variants as pathogenic based on the combined scores of commonly used in-silico tools tools—MutationTaster2, Polyphen2, and MutPred2. Among these 76 variants, three (p.S336Y, p.Y347H, p.Y350H) were identified to be located in post-translational modification and regulatory protein binding sites, suggesting their potential as putative functional variants. Moreover, we obtained strong evidence for rs112948541 and rs767232322 variants being as regulatory important. Additionally, we identified 16 miRNA target sites for the two variants (rs200040454 and rs144308510) in the 3' untranslated region of the GPRC5A. The results of in-silico analyses highlight the functional importance of the GPRC5A variants that may contribute to the GPRC5A-associated cancer types and the importance of in vivo evaluation to reveal their role in human cancer.
Publisher
Research Square Platform LLC