In summary, we corroborated that the functional variant of rs653765 acts as an important genetic factor that confers the progression of sepsis in a large cohort and revealed that the rs653765 G→A variants modulate ADAM10 promoter activity by altering the binding of the EGR1 to the ADAM10 promoter, which then functionally activates ADAM10 gene expression and may influence the prognosis of sepsis. Here, EGR1 is linked to Sepsis.