CUBN gene

The CUBN gene provides instructions for making the protein cubilin, which is essential for the absorption of vitamin B12 and the reabsorption of proteins in the kidneys.

Normal Function

The CUBN gene provides instructions for making a protein called cubilin. This protein helps the body absorb vitamin B12 (also called cobalamin) from food, which is important because the body cannot make this vitamin. Vitamin B12 is essential for the formation of DNA and for the chemical reactions that convert food into energy (energy metabolism). Vitamin B12 also plays a key role in making red blood cells and maintaining the nerve cells in the brain and spinal cord (central nervous system).

Cubilin binds to another protein called amnionless to form a complex called the cubam receptor, which is present in the kidneys and the small intestine. In the small intestine, cubilin interacts with vitamin B12 while it is anchored to the cell membrane by amnionless.

During digestion, vitamin B12 binds to intrinsic factor, which helps the intestines absorb vitamin B12. Vitamin B12 and intrinsic factor then bind to cubilin as they pass through the small intestine. Amnionless helps transfer this whole complex into the intestinal cells. Vitamin B12 is then released into the blood and travels throughout the body. In the kidneys, amnionless and cubilin help return proteins to the bloodstream (reabsorption) that would otherwise be released in the urine.

Health Conditions Related to Genetic Changes

Imerslund-Gräsbeck syndrome

Changes in the CUBN gene cause Imerslund-Gräsbeck syndrome. Genetic changes that cause disease are called pathogenic variants. Imerslund-Gräsbeck syndrome is characterized by problems with the body's ability to absorb vitamin B12, which can lead to a blood disorder known as megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia) and the remaining red blood cells are larger than normal (megaloblastic). Affected individuals frequently have excess protein in their urine (proteinuria).

Many of the pathogenic variants that are associated with Imerslund-Gräsbeck syndrome cause cells to produce an altered version of cubilin that prevents the protein from traveling to the cell membrane. This impairs the intestinal absorption of vitamin B12 and reduces the amount of vitamin B12 that is available for the body to use. A shortage of vitamin B12 affects the development of red blood cells, leading to megaloblastic anemia. When there is not enough cubilin in the membranes of kidney cells, proteins are released in the urine instead of being reabsorbed into the body.