TPP1 gene

tripeptidyl peptidase 1

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. This enzyme 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.

Genetics Home Reference provides information about juvenile Batten disease.

At least 100 mutations in the TPP1 gene have been found to cause late-infantile neuronal ceroid lipofuscinosis (NCL). This condition impairs motor and mental development beginning in early childhood, causing 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 change single amino acids in tripeptidyl peptidase 1, resulting in a severe decrease in enzyme activity. One of two mutations, written as IV5-1G>C and R508X, causes nearly 90 percent of cases of late-infantile NCL worldwide.

Fatty substances called lipopigments accumulate in the lysosomes of people with late-infantile NCL. These accumulations can result in cell dysfunction and eventually cause cell death, especially in brain cells, which are particularly vulnerable to damage caused by lipopigments. However, it is unclear how mutations in the TPP1 gene are involved in the buildup of lipopigments and the signs and symptoms of late-infantile NCL.

Cytogenetic Location: 11p15.4, which is the short (p) arm of chromosome 11 at position 15.4

Molecular Location: base pairs 6,612,766 to 6,619,461 on chromosome 11 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 11p15.4, which is the short (p) arm of chromosome 11 at position 15.4
  • cell growth-inhibiting gene 1 protein
  • CLN2
  • GIG1
  • growth-inhibiting protein 1
  • LPIC
  • lysosomal pepstatin insensitive protease
  • TPP-1
  • tripeptidyl aminopeptidase
  • tripeptidyl-peptidase 1
  • tripeptidyl-peptidase 1 preproprotein
  • tripeptidyl peptidase I