Bengaluru: Scientists are gaining a remarkable opportunity to understand the human body by studying people whose genes have naturally stopped working.
A large study from Pakistan, published in Nature in June 2026, identified naturally occurring “human knockouts” on an unprecedented scale. Among 1,73,303 participants, around one in five carried at least one gene in which both copies had loss-of-function variants.
What are knockout genes?
Humans generally inherit two copies of most genes, one from each parent. Sometimes, changes in both copies can prevent a gene from functioning.
Yet some people carrying these changes appear healthy and lead ordinary lives. Their genetic makeup offers researchers a rare opportunity to observe what happens when a particular biological instruction is effectively switched off.
The Pakistani study identified such knockouts across 6,476 genes — nearly one-third of the approximately 20,000 protein-coding genes in humans.
Nature provides a natural experiment
These individuals can help researchers determine whether the absence of a gene causes disease, provides an advantage or has little noticeable effect.
The findings could eventually help identify biological pathways involved in immunity, metabolism and other conditions. Such information may also guide the development of medicines that deliberately block or reduce the activity of specific proteins.
Why family genetics matters
These genetic patterns can be more common in populations where marriage between relatives has occurred over generations. When parents share an ancestor, they may carry the same rare variant, increasing the possibility that a child inherits two copies.
This does not mean that every inactive gene causes illness. In fact, the absence of obvious disease in many participants is precisely what makes these genetic “experiments” valuable.
Researchers hope such discoveries will improve understanding of human biology and help identify new approaches to preventing and treating disease.