Short protein sequences have the potential to greatly broaden our understanding of the human genome, acting as a valuable source of undiscovered biological information.

The possibility of expanding the universe of human genes by up to one-third exists if a determined effort to discover new genes that encode short proteins succeeds. This effort, announced in Nature Biotechnology, aims to compile a catalog of new miniproteins and determine their functions, which could provide insights into various biochemical processes and potential targets for novel medications. Researchers believe that exploring the microproteome could uncover previously unexplored aspects of biology with significant implications for understanding genetics and disease. The current catalog of human genes includes only those that code for proteins containing at least 100 amino acids each, overlooking the existence of smaller proteins that have demonstrated essential roles in immune regulation, protein blocking, and RNA degradation. By using alternative techniques such as Ribo-seq, which sequences and catalogs RNAs bound to ribosomes, researchers have identified thousands of open reading frames (ORFs) that may represent new proteins. The consortium has identified 7,264 candidate ORFs from Ribo-seq databases and plans to determine their cellular functions using techniques like mass spectrometry and epitope tagging. Although the effort is currently being funded by participating investigators’ own lab budgets, there may be a need for dedicated funding in the future.