Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Illuminating the Druggable Genome: an NIH Common Fund Program (#721)

Mehdi Mesri 1 , Christine Colvis 1 , Aaron Pawlyk 1
  1. National Institutes of Health (NIH), Bethesda, MD, United States

Existing clinical drugs only target a few hundred of the ~3000 “druggable genome,”, leaving a large subset within this druggable genome that remain largely understudied.  Three protein families, the ion channels, G-protein-coupled receptors and protein kinases, have been identified to contain adequate numbers (~400 proteins) of understudied members and are well-established druggable families with high potential to impact human health.

To improve our scientific understanding of understudied members of these three protein families, the National Institutes of Health (NIH) Common Fund launched the Illuminating the Druggable Genome (IDG) Program in 2014.  The Pilot Phase of the Program (2014-2017) established scalable technology platforms, and developed a website, Pharos (, that aggregates protein information from several sources, allowing researchers easy access to in depth protein data. Now in its Implementation Phase (2017-2024), the IDG Program aims to build on the knowledge and tools developed during the Pilot Phase and to generate, aggregate, analyze, and disseminate knowledge and tools around understudied proteins. 

The kinase team, a working group of six laboratories, have constructed a heavy amino acid-labeled peptide library encoding tryptic fragments of dark kinases to quantitatively monitor their abundance in normal and perturbed cells using parallel reaction monitoring with stable isotope dilution (PRM-SID). The PRM-mass spec analysis is done in parallel with RNASeq, and data analyzed using network inference tools to provide insight into dark kinase integration in diverse cell types in response to genetic and pharmacological perturbations. The experimental work and reagents developed by the Kinase team is maintained in a comprehensive manner in the Dark Kinase Knowledgebase (DKK) that can be accessed at

These new knowledge and tool sets are intended to equip the scientific community, including small businesses and the pharmaceutical industry, with the ability to explore previously understudied biology with the potential to rapidly impact human health.