LAMP2
lysosomal associated membrane protein 2
Normal Function
Health Conditions Related to Genetic Changes
Danon disease
More than a hundred variants (also called mutations) in the LAMP2 gene have been found to cause Danon disease. Danon disease is a condition characterized by weakening of the heart muscle (cardiomyopathy), weakening of skeletal muscles (myopathy), and intellectual disabilities.
The LAMP2 gene variants that cause Danon disease lead to the production of very little or no functional LAMP-2 protein. Most variants affect all three isoforms of the LAMP-2 protein. However, variants that affect only the LAMP-2B isoform also cause Danon disease, likely because this isoform is largely found in muscle and heart cells.
Studies have shown that in cells without the LAMP-2 protein, fusion between autophagic vacuoles and lysosomes occurs more slowly, which leads to the accumulation of autophagic vacuoles. People with Danon disease have an abnormally large number of autophagic vacuoles in their heart and skeletal muscle cells. This accumulation likely leads to the breakdown of these cells, causing the heart problems and muscle weakness seen in people with Danon disease. The cause of the other signs and symptoms of Danon disease is unclear, but it is likely related to the accumulation of vacuoles in other affected tissues.
Some people with LAMP2 gene variants develop hypertrophic cardiomyopathy without the other characteristic features of Danon disease. Hypertrophic cardiomyopathy is a thickening of the heart muscle that may make it harder for the heart to pump blood. In people with LAMP2 gene mutations, the lower left chamber of the heart, called the left ventricle, is usually the affected region. People with hypertrophic cardiomyopathy caused by LAMP2 gene variants often have cardiac preexcitation, which is an abnormality of the electrical signals that control the heartbeat. It is unclear whether this is a separate condition or a milder form of Danon disease. Furthermore, it is unknown why some people with LAMP2 gene variants develop hypertrophic cardiomyopathy but not the other features of Danon disease.
People who have a LAMP2 gene variant are thought to account for 1 to 4 percent of individuals with hypertrophic cardiomyopathy.
More About This Health ConditionRelated Conditions
Danon disease
Health Conditions Related to Genetic Changes
More than a hundred variants (also called mutations) in the LAMP2 gene have been found to cause Danon disease. Danon disease is a condition characterized by weakening of the heart muscle (cardiomyopathy), weakening of skeletal muscles (myopathy), and intellectual disabilities.
The LAMP2 gene variants that cause Danon disease lead to the production of very little or no functional LAMP-2 protein. Most variants affect all three isoforms of the LAMP-2 protein. However, variants that affect only the LAMP-2B isoform also cause Danon disease, likely because this isoform is largely found in muscle and heart cells.
Studies have shown that in cells without the LAMP-2 protein, fusion between autophagic vacuoles and lysosomes occurs more slowly, which leads to the accumulation of autophagic vacuoles. People with Danon disease have an abnormally large number of autophagic vacuoles in their heart and skeletal muscle cells. This accumulation likely leads to the breakdown of these cells, causing the heart problems and muscle weakness seen in people with Danon disease. The cause of the other signs and symptoms of Danon disease is unclear, but it is likely related to the accumulation of vacuoles in other affected tissues.
Some people with LAMP2 gene variants develop hypertrophic cardiomyopathy without the other characteristic features of Danon disease. Hypertrophic cardiomyopathy is a thickening of the heart muscle that may make it harder for the heart to pump blood. In people with LAMP2 gene mutations, the lower left chamber of the heart, called the left ventricle, is usually the affected region. People with hypertrophic cardiomyopathy caused by LAMP2 gene variants often have cardiac preexcitation, which is an abnormality of the electrical signals that control the heartbeat. It is unclear whether this is a separate condition or a milder form of Danon disease. Furthermore, it is unknown why some people with LAMP2 gene variants develop hypertrophic cardiomyopathy but not the other features of Danon disease.
People who have a LAMP2 gene variant are thought to account for 1 to 4 percent of individuals with hypertrophic cardiomyopathy.