Should pharmacologists care about alternative splicing? IUPHAR Review 4


  • T I Bonner

    Corresponding author
    1. National Institute of Mental Health, Bethesda, MD, USA
    • Correspondence

      Tom I. Bonner, Office of the Scientific Director, NIMH, 49 Convent Drive, Bldg 49, Rm B1B80, MSC4405, Bethesda MD 20892-4405, USA. E-mail:

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  • Tom Bonner is a member of the Evolving Pharmacology Group of the Nomenclature Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR). The role of this group is to monitor the ‘de-orphanisation’ of orphan GPCRs, to classify the remaining orphan receptors and to define the criteria used to recommend the pairing of an orphan receptor with its cognate ligand(s). Further information can be found on the IUPHAR/BPS Guide to PHARMACOLOGY website ( This has recently been updated to reflect the current state of orphan GPCRs in each of the three classes, and has the latest information on new pairings under the ‘Recent receptor-ligand pairings’ section.


Alternative splicing of mRNAs occurs in the majority of human genes, and most differential splicing results in different protein isoforms with possibly different functional properties. However, there are many reported splicing variations that may be quite rare, and not all combinatorially possible variants of a given gene are expressed at significant levels. Genes of interest to pharmacologists are frequently expressed at such low levels that they are not adequately represented in genome-wide studies of transcription. In single-gene studies, data are commonly available on the relative abundance and functional significance of individual alternatively spliced exons, but there are rarely data that quantitate the relative abundance of full-length transcripts and define which combinations of exons are significant. A number of criteria for judging the significance of splice variants and suggestions for their nomenclature are discussed.