SERPINC1

The SERPINC1 gene provides instructions for making a protein called antithrombin (previously known as antithrombin III), which is a type of serine protease inhibitor (serpin). Serpins help control several types of chemical reactions by blocking the activity of certain proteins. Antithrombin is found in the bloodstream and is important for controlling blood clotting.

Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin. Antithrombin attaches (binds) to thrombin and certain other clotting proteins, which are then cleared from the bloodstream by the liver.

While one part of antithrombin binds to thrombin and other clotting proteins, another part of the protein binds to a substance called heparin. Antithrombin changes its shape when it binds to heparin. This change in shape allows antithrombin to inactivate clotting proteins at a much faster rate.

hereditary antithrombin deficiency - caused by mutations in the SERPINC1 gene

At least 220 mutations in the SERPINC1 gene have been found to cause hereditary antithrombin deficiency. Most of these mutations change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting.

Hereditary antithrombin deficiency can be divided into type I and type II based on the mutation in the SERPINC1 gene.

Hereditary antithrombin deficiency type I is caused by SERPINC1 gene mutations that prevent the cell from producing antithrombin from the altered gene. Individuals with this type have only one working copy of the SERPINC1 gene in each cell, which results in approximately half of the normal amount of antithrombin. Affected individuals do not have enough antithrombin to inactivate clotting proteins, which causes the increased risk for abnormal blood clots in hereditary antithrombin deficiency.

Mutations that cause hereditary antithrombin deficiency type II result in the production of an altered antithrombin with reduced activity. Individuals with this form of the condition typically have normal levels of antithrombin, but the protein does not function properly. Type II can be further divided based on whether the mutation affects binding to thrombin and other clotting factors (type IIa), heparin (type IIb), or both (type IIc). Individuals with hereditary antithrombin deficiency type IIb have a lower risk of forming an abnormal blood clot than people with other forms of this condition because antithrombin is able to inactivate clotting proteins without heparin.