TNNI3

The TNNI3 gene provides instructions for making a protein called troponin I-cardiac isoform, which is found solely in the heart (cardiac) muscle. Troponin I-cardiac isoform is one of three proteins that make up the troponin protein complex found in cardiac muscle cells. This complex, along with calcium, regulates tensing (contraction) of cardiac muscle.

Troponin I-cardiac isoform is responsible for relaxation of the heart muscle following contraction. For the heart to beat normally, cardiac muscle must contract and relax in a coordinated way. When calcium levels are low, troponin I-cardiac isoform attaches (binds) to a protein called actin, which leads to relaxation of the heart muscle. An increase in calcium levels causes structural changes in another troponin protein called troponin C, which then triggers troponin I-cardiac isoform to detach from actin, allowing the heart muscle to contract.

familial restrictive cardiomyopathy - caused by mutations in the TNNI3 gene

Approximately 10 mutations in the TNNI3 gene have been found to cause familial restrictive cardiomyopathy. Most of these mutations change single protein building blocks (amino acids) in the troponin I-cardiac isoform protein, which impairs the protein's function. The altered protein typically cannot bind to actin. As a result, heart muscle relaxation is disrupted, leading to abnormal heart action and blood flow and the signs and symptoms of familial restrictive cardiomyopathy.

other disorders - caused by mutations in the TNNI3 gene

Mutations in the TNNI3 gene can also cause other heart conditions called hypertrophic cardiomyopathy type 7 and dilated cardiomyopathy types 2A and 1FF. Hypertrophic cardiomyopathy is a thickening of the cardiac muscle that forces the heart to work harder to pump blood. This condition is often associated with an abnormal heartbeat (arrhythmia) and can lead to heart failure and sudden death. In some people, hypertrophic cardiomyopathy transforms into restrictive cardiomyopathy, although it can be difficult to distinguish these two disorders. Dilated cardiomyopathy is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Dilated cardiomyopathy also increases the risk of heart failure and premature death.