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Toward the next step in G protein-coupled receptor research: a knowledge-driven analysis for the next potential targets in drug discovery.
Journal of Structural and Functional Genomics 2016 December
More than 800 G protein-coupled receptor (GPCR) genes have been discovered in the human genome. Towards the next step in GPCR research, we performed a knowledge-driven analysis of orphan class-A GPCRs that may serve as novel targets in drug discovery. We examined the relationship between 61 orphan class-A GPCR genes and diseases using the Online Mendelian Inheritance in Man (OMIM) database and the DDSS tool. The OMIM database contains data on disease-related variants of the genes. Particularly, the variants of GPR101, GPR161, and GPR88 are related to the genetic diseases: growth hormone-secreting pituitary adenoma 2, pituitary stalk interruption syndrome (not confirmed), and childhood-onset chorea with psychomotor retardation, respectively. On the other hand, the Drug Discovery and Diagnostic Support System (DDSS) tool suggests that 48 out of the 61 orphan receptor genes are related to diseases, judging from their co-occurrences in abstracts of biomedical literature. Notably, GPR50 and GPR3 are related to as many as 25 and 24 disease-associated keywords, respectively. GPR50 is related to 17 keywords of psychiatric disorders, whereas GPR3 is related to 11 keywords of neurological disorders. The aforementioned five orphan GPCRs were characterized genetically, structurally and functionally using the structural life science data cloud VaProS, so as to evaluate their potential as next targets in drug discovery.
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