ArticleThe Journal of biological chemistry2019
Rare-variant pathogenicity triage and inclusion of synonymous variants improves analysis of disease associations of orphan G protein-coupled receptors.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Rare GPR37L1 Variants Reveal Potential Association between GPR37L1 and Disorders of Anxiety and Migraine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Article
- Role of GPR39 in Neurovascular Homeostasis and Disease.International journal of molecular sciences · 2021Review
- The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.International journal of molecular sciences · 2021Review
- GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment.Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Natural Selection Shapes Codon Usage in the Human Genome.American journal of human genetics · 2020Article
- Novel approaches leading towards peptide GPCR de-orphanisation.British journal of pharmacology · 2020Review
- Quantitative Proteomics Reveal an Altered Pattern of Protein Expression in Brain Tissue from Mice Lacking GPR37 and GPR37L1.Journal of proteome research · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pace of deorphanization of G protein-coupled receptors (GPCRs) has slowed, and new approaches are required. Small molecule targeting of orphan GPCRs can potentially be of clinical benefit even if the endogenous receptor ligand has not been identified. Many GPCRs lack common variants that lead to reproducible genome-wide disease associations, and rare-variant approaches have emerged as a viable alternative to identify disease associations for such genes. Therefore, our goal was to prioritize orphan GPCRs by determining their associations with human diseases in a large clinical population. We used sequence kernel association tests to assess the disease associations of 85 orphan or understudied GPCRs in an unselected cohort of 51,289 individuals. Using rare loss-of-function variants, missense variants predicted to be pathogenic or likely pathogenic, and a subset of rare synonymous variants that cause large changes in local codon bias as independent data sets, we found strong, phenome-wide disease associations shared by two or more variant categories for 39% of the GPCRs. To validate the bioinformatics and sequence kernel association test analyses, we functionally characterized rare missense and synonymous variants of GPR39, a family A GPCR, revealing altered expression or Zn
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.