Giovanna Weykopf was poring over genetic data when she noticed something invisible to most: a tiny shift in a previously overlooked protein that could change how we understand lung disease. Her discovery, led by researchers at the University of Edinburgh and the University of Sydney, has uncovered a hidden player in severe COVID-19 and lung fibrosis—a genetic variant carried by nearly one in three people that alters the function of a newly identified lung enzyme. This breakthrough, published in Nature Communications, doesn’t just rewrite the story of one protein; it challenges decades of genetic research that may have missed crucial links between DNA and disease.
For years, scientists have mapped disease risk by studying known proteins encoded in the human genome’s 20,000 genes. But many of these genes produce multiple proteins, some tissue-specific and long overlooked. The team found that genetic variants once thought harmless actually disrupt these newly discovered molecules—especially in poorly understood regions of the genome. Using a novel method capable of detecting proteins even at extremely low levels, the researchers zeroed in on one enzyme in lung tissue linked to infection, inflammation, and lung cancer. The variant alters its function and even changes how it responds to drugs, offering a biological explanation for why some people face higher risks during respiratory illness.
The implications stretch far beyond the lungs. The team identified similar hidden proteins influenced by genetic changes tied to vitamin D regulation, kidney disease, and heart conditions. Some variants are remarkably common—up to 50% of people carry them—though their individual effects may be small. Others are vanishingly rare, appearing in as few as one in a million individuals, yet likely causing severe disease when present. This spectrum suggests that many undiagnosed or poorly understood conditions could stem from proteins only recently detected.
"For decades, we have interpreted genetic variation through the lens of the proteins we knew existed," says Dr. Simon Biddie of the University of Edinburgh’s Institute of Genetics and Cancer. "Our findings show that many genetic changes linked to disease may actually act through previously hidden proteins that have only recently come to light." The work, co-involving Professor Mark Gorrell of the Centenary Institute and the University of Sydney—who first discovered the enzyme—opens new paths not just for diagnosis, but for designing treatments that target these once-invisible molecules.
As genetic science moves beyond the well-mapped, the real impact may lie in the overlooked corners of our DNA. With tools now capable of illuminating these hidden proteins, researchers are poised to turn genetic mysteries into medical breakthroughs—one overlooked molecule at a time.