CCDC40 gene
The CCDC40 gene is essential for the assembly of structures that allow cilia and flagella to move, playing a critical role in respiratory and reproductive health.
Normal Function
The CCDC40 gene provides instructions for making a protein that is involved in the assembly of a larger group of proteins (a complex) called dynein. Dynein functions within cell structures called cilia and flagella. Cilia are microscopic, finger-like projections that stick out from the surface of cells. Coordinated back and forth movement of cilia can move the cell or the fluid surrounding the cell. Flagella are similar to cilia, but flagella are found only in sperm cells. Dynein makes up the structures (arms) that produce the force needed for cilia and flagella to move.
Dynein forms structures known as inner dynein arms (IDAs) and outer dynein arms (ODAs) within the core of cilia and flagella (the axoneme). Coordinated movement of the dynein arms causes the entire axoneme to bend back and forth. The CCDC40 protein is necessary for the proper assembly of the IDAs, which play a central role in the coordinated movement of cilia and flagella.
Researchers suspect that the CCDC40 protein is also involved in the proper assembly of the nexin-dynein regulatory complex, which helps regulate and coordinate the activity of the inner and outer dynein arms. By helping with the assembly of both the IDAs and the nexin-dynein regulatory complex, the CCDC40 protein plays a central role in the coordinated movement of cilia and flagella.
Health Conditions Related to Genetic Changes
Primary ciliary dyskinesia
Variants (also called mutations) in the CCDC40 gene have been found to cause primary ciliary dyskinesia, which is characterized by respiratory tract infections, abnormally positioned internal organs, and difficulties having biological children (decreased fertility). The variants in the CCDC40 gene that are associated with primary ciliary dyskinesia cause cells to produce fewer functional CCDC40 proteins. The lack of functional CCDC40 protein impairs the assembly of the IDAs and the nexin-dynein regulatory complex, both of which are necessary for the coordinated back and forth movement of cilia. The disruption of the movement of cilia leads to the various signs and symptoms of primary ciliary dyskinesia.