SERPING1

The SERPING1 gene provides instructions for making a protein called C1 inhibitor, which is a type of serine protease inhibitor (serpin). Serpins help control several types of chemical reactions by blocking the activity of certain proteins. C1 inhibitor is important for controlling a range of processes involved in maintaining blood vessels, including inflammation. Inflammation is a normal body response to infection, irritation, or other injury.

C1 inhibitor blocks the activity of several proteins in the blood, including plasma kallikrein and the activated form of factor XII (called factor XIIa). These two proteins are involved in the production of bradykinin. Bradykinin is a protein that promotes inflammation by increasing the permeability of blood vessel walls, allowing fluids to leak into body tissues. C1 inhibitor attaches (binds) to plasma kallikrein and factor XIIa, which prevents them from completing any further reactions. These proteins are cleared from the bloodstream once they are bound to C1 inhibitor.

hereditary angioedema - caused by mutations in the SERPING1 gene

More than 250 mutations in the SERPING1 gene have been found to cause hereditary angioedema types I and II. Mutations that cause type I occur throughout the gene and lead to reduced levels of C1 inhibitor in the blood. Mutations that cause type II usually occur in a specific region of the gene called exon 8 and result in the production of a C1 inhibitor that functions abnormally. Without the proper levels of functional C1 inhibitor, the activity of plasma kallikrein and factor XIIa cannot be blocked and excessive amounts of bradykinin are produced. Excess fluids leak through blood vessel walls and accumulate in body tissues, leading to the recurrent episodes of swelling seen in individuals with hereditary angioedema type I and type II.