TPM3

The TPM3 gene provides instructions for making a protein called slow muscle alpha (α)-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.

Slow muscle α-tropomyosin is found in skeletal muscles, which are the muscles used for movement. Skeletal muscle is made up of two types of muscle fibers: type I (slow twitch fibers) and type II (fast twitch fibers). Slow muscle α-tropomyosin is found only in type I fibers. Type I fibers are the primary component of skeletal muscles that are resistant to fatigue. For example, muscles involved in posture, such as the neck muscles that hold the head steady, are made predominantly of type I fibers. Slow muscle α-tropomyosin helps regulate muscle contraction in type I skeletal muscle fibers.

cap myopathy - caused by mutations in the TPM3 gene

At least two TPM3 gene mutations have been identified in people with cap myopathy. These mutations replace the protein building block (amino acid) arginine with the amino acids cysteine or histidine at position 168 of the protein sequence, written as Arg168Cys or Arg168His (also written as R168C or R168H). The specific effects of these TPM3 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.

congenital fiber-type disproportion - caused by mutations in the TPM3 gene

At least 10 mutations in the TPM3 gene have been found to cause congenital fiber-type disproportion. TPM3 gene mutations appear to be the most common cause of this disorder. These mutations change single amino acids in slow muscle α-tropomyosin. The TPM3 gene mutations that cause congenital fiber-type disproportion are thought to impair the protein's ability to interact with myosin and actin within type I skeletal muscle fibers, disrupting muscle contraction. Inefficient muscle contraction leads to muscle weakness and the other features of congenital fiber-type disproportion.

other disorders - caused by mutations in the TPM3 gene

Mutations in the TPM3 gene are also associated with a condition called nemaline myopathy. People with nemaline myopathy typically have muscle weakness throughout their body, including the muscles of the face, neck, and limbs. When nemaline myopathy is caused by mutations in the TPM3 gene, affected individuals typically have muscle weakness at birth or beginning in early childhood. TPM3 gene mutations account for a small percentage of all cases of nemaline myopathy.