TPM2

The TPM2 gene provides instructions for making a protein called beta (β)-tropomyosin, which is part of the tropomyosin protein family. Tropomyosin proteins regulate the tensing of muscle fibers (muscle contraction) by controlling the binding of two muscle proteins, myosin and actin. In non-muscle cells, tropomyosin proteins play a role in controlling cell shape.

β-tropomyosin is found primarily in skeletal muscles, which are the muscles used for movement. This protein helps regulate muscle contraction by interacting with other muscle proteins, particularly myosin and actin. These interactions are essential for stabilizing and maintaining structures called sarcomeres within muscle cells. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract.

cap myopathy - caused by mutations in the TPM2 gene

At least three TPM2 gene mutations have been identified in people with cap myopathy. These mutations delete or duplicate genetic material in the TPM2 gene or replace single protein building blocks (amino acids) in the β-tropomyosin protein sequence. The specific effects of these TPM2 gene mutations are unclear, but researchers suggest they may interfere with normal actin-myosin binding, impairing muscle contraction and resulting in the muscle weakness that occurs in cap myopathy.

distal arthrogryposis type 1 - caused by mutations in the TPM2 gene

At least one mutation in the TPM2 gene has been found to cause distal arthrogryposis type 1, a disorder characterized by joint deformities (contractures) in the hands and feet. The mutation changes a single amino acid in the β-tropomyosin protein. Specifically, it replaces the amino acid arginine with the amino acid glycine at protein position 91 (written as Arg91Gly or R91G). It is unclear how the defective protein leads to contractures in people with distal arthrogryposis type 1, or why the joint problems are typically limited to the hands and feet. However, researchers speculate that contractures may be related to problems with muscle contraction that limit the movement of joints before birth.

other disorders - caused by mutations in the TPM2 gene

TPM2 gene mutations have also been found to cause several other muscle disorders (myopathies), including nemaline myopathy and a more severe form of distal arthrogryposis known as type 2B. These disorders are characterized by muscle weakness and problems with movement. Because their signs and symptoms are present from birth, these disorders are known as congenital myopathies.

Most of the mutations that have been identified in the TPM2 gene change single amino acids in the β-tropomyosin protein. Mutations in this gene likely alter the structure of β-tropomyosin and disrupt the protein's normal function. However, the mechanism by which defective β-tropomyosin causes muscle weakness is unknown. Researchers are working to determine how different mutations in the TPM2 gene lead to different congenital myopathies.

Genetics Home Reference provides information about nemaline myopathy, which is also associated with changes in the TPM2 gene.