Journal of Structural and Functional Genomics

, Volume 17, Issue 4, pp 111–133 | Cite as

Toward the next step in G protein-coupled receptor research: a knowledge-driven analysis for the next potential targets in drug discovery

  • Koji Nagata
  • Yukie Katayama
  • Tomomi Sato
  • Yeondae Kwon
  • Takeshi Kawabata
Article
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Abstract

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.

Keywords

DDSS OMIM Orphan GPCR VaProS 
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Notes

Acknowledgements

This work was supported by the Platform for Drug Discovery, Informatics, and Structural Life Science (PDIS) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and Japan Agency for Medical Research and Development (AMED). This research used VaProS, a data-cloud developed by the Information Core of PDIS from MEXT and AMED.

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Koji Nagata
    • 1
  • Yukie Katayama
    • 1
  • Tomomi Sato
    • 2
  • Yeondae Kwon
    • 1
  • Takeshi Kawabata
    • 3
  1. 1.Department of Applied Biological Chemistry, Graduate School of Agricultural and Life SciencesThe University of TokyoTokyoJapan
  2. 2.Structural Biology Research Center, Photon Factory, Institute of Materials Structure ScienceHigh Energy Accelerator Research Organization (KEK)TsukubaJapan
  3. 3.Institute for Protein ResearchOsaka UniversitySuita, OsakaJapan

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