Zygotic lethal gene: A gene that is lethal (fatal) for the zygote, the cell formed by the union of a sperm (male sex cell) and an ovum (female sex cell). The zygote would normally develop into an embryo, as instructed by the genetic material within the unified cell. However, a zygotic lethal gene scotches prenatal development at its earliest point.

A zygotic lethal gene is a mutated (changed) version of a normal gene essential to the survival of the zygote. The extent of the mutation can range from a change in a single base in the DNA to deletion (loss) of the entire gene.