TPP1 gene
The TPP1 gene provides instructions for creating the tripeptidyl peptidase 1 enzyme, which is vital for breaking down proteins within cellular structures called lysosomes.
Normal Function
The TPP1 gene provides instructions for making an enzyme called tripeptidyl peptidase 1. This enzyme is produced as an inactive enzyme, called a proenzyme, which has an extra segment attached. This segment must be removed, followed by additional processing steps, for the enzyme to become active. The active tripeptidyl peptidase 1 enzyme is found in cell structures called lysosomes, which digest and recycle different types of molecules. Tripeptidyl peptidase 1 acts as a peptidase, which means that it breaks down protein fragments, known as peptides, into their individual building blocks (amino acids). Specifically, tripeptidyl peptidase 1 cuts (cleaves) peptides into groups of three amino acids.
Health Conditions Related to Genetic Changes
CLN2 disease
At least 115 mutations in the TPP1 gene have been found to cause CLN2 disease. This condition impairs motor and mental development, typically starting in early childhood, causing gradually worsening movement disorders and a decline in intellectual function. In addition, affected children often develop recurrent seizures (epilepsy) and vision impairment.
Most of the TPP1 gene mutations that cause CLN2 disease change single amino acids in tripeptidyl peptidase 1, resulting in a severe decrease in enzyme activity. A reduction in functional enzyme results in the incomplete breakdown of certain peptides. CLN2 disease is characterized by the accumulation of proteins or peptides and other substances in lysosomes. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. The accumulations can cause cell damage leading to cell death. The progressive death of nerve cells in the brain and other tissues leads to the signs and symptoms of CLN2 disease.
Other disorders
Mutations in the TPP1 gene have also been found to cause spinocerebellar ataxia, autosomal recessive 7 (SCAR7), which is a condition characterized by progressive problems with movement. During childhood, individuals with SCAR7 develop walking difficulties; impaired speech (dysarthria); and eye movement problems, such as involuntary movement of the eyes (nystagmus), rapid eye movements (saccades), and trouble moving the eyes side-to-side (oculomotor apraxia). People with SCAR7 have progressive loss of cells (atrophy) of various parts of the brain, particularly within the cerebellum.