PPT1 gene

palmitoyl-protein thioesterase 1

The PPT1 gene provides instructions for making an enzyme called palmitoyl-protein thioesterase 1. This enzyme is found in structures called lysosomes, which are compartments within cells that break down and recycle different types of molecules. Palmitoyl-protein thioesterase 1 removes certain fats called long-chain fatty acids from proteins, which probably helps break down the proteins. Palmitoyl-protein thioesterase 1 is also thought to be involved in a variety of other cell functions.

More than 50 mutations in the PPT1 gene have been found to cause infantile neuronal ceroid lipofuscinosis (NCL). This condition impairs mental and motor development beginning between the first and second year of life, causing difficulty with walking, speaking, and intellectual function. In addition, affected children often develop recurrent seizures (epilepsy) and vision impairment. The PPT1 gene mutations that cause infantile NCL decrease the production or function of palmitoyl-protein thioesterase 1. The most common mutation causing infantile NCL worldwide, written as R151X, replaces the protein building block (amino acid) arginine with a premature stop signal in the instructions used to make the enzyme. This mutation results in an abnormally short, nonfunctional enzyme. Another mutation is responsible for most cases of the disorder in people of Finnish descent; this genetic change replaces arginine with the amino acid tryptophan at position 122 in the palmitoyl-protein thioesterase 1 enzyme (written as R122W).

PPT1 gene mutations that cause infantile NCL lead to a severe reduction of functional enzyme, which impairs the removal of fatty acids from proteins. In the lysosomes, these fats and proteins accumulate into fatty substances called lipopigments. These accumulations occur in cells throughout the body, but nerve cells in the brain seem to be particularly vulnerable to damage caused by the buildup of lipopigments and reduction of enzyme function. The progressive death of cells, especially in the brain, leads to the signs and symptoms of infantile NCL.

Genetics Home Reference provides information about juvenile Batten disease.

At least four mutations in the PPT1 gene have been found to cause Kufs disease type A. This condition is a type of NCL characterized by seizures, progressive problems with movement, and a decline in intellectual function beginning in adulthood. These mutations change single amino acids or create a premature stop signal in the instructions used to make palmitoyl-protein thioesterase 1. The PPT1 gene mutations that cause Kufs disease allow enough functional protein to be produced so that signs and symptoms of the disorder do not develop until later in life.

A decrease in the normal amount of palmitoyl-protein thioesterase 1 slows the breakdown of fatty acids and proteins. The materials accumulate over time into lipopigments in the lysosomes of nerve cells in the brain. These accumulations can result in cell dysfunction and eventually cause cell death. The death of nerve cells in the brain causes the movement problems and intellectual decline characteristic of Kufs disease.

At least 10 mutations that cause late-infantile NCL have been identified in the PPT1 gene. This form of NCL impairs motor and mental development beginning in early childhood, causing movement disorders and a decline in intellectual function. In addition, affected children often develop epilepsy and vision impairment. Most of the PPT1 gene mutations that cause late-infantile NCL greatly reduce the activity of palmitoyl-protein thioesterase 1. A shortage of normal enzyme impairs the removal of fatty acids from proteins and causes the accumulation of these substances as lipopigments in lysosomes. A buildup of lipopigments in cells often results in cell dysfunction and can eventually cause cell death, especially in brain cells, which are vulnerable to damage. Over time, the death of cells, especially in the brain, leads to the signs and symptoms of late-infantile NCL.

Cytogenetic Location: 1p34.2, which is the short (p) arm of chromosome 1 at position 34.2

Molecular Location: base pairs 40,072,710 to 40,097,470 on chromosome 1 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 1p34.2, which is the short (p) arm of chromosome 1 at position 34.2
  • ceriod-lipofuscinosis, neuronal 1
  • CLN1
  • INCL
  • palmitoyl-protein hydrolase 1
  • PPT
  • PPT-1
  • PPT1_HUMAN