PPT1 Gene (Palmitoyl-Protein Thioesterase 1)
Genetic and Functional Insights into PPT1, a Lysosomal Enzyme Implicated in Neuronal Ceroid Lipofuscinosis
Gene Information Card
| Symbol | PPT1 |
|---|---|
| Full Name | Palmitoyl-protein thioesterase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 5538 ncbi.nlm.nih.gov/gene/5538 |
| Ensembl ID | ENSG00000131238 |
| UniProt ID | P50897 |
| OMIM ID | 600722 |
| HGNC ID | 9325 |
| Aliases | CLN1, INCL, PPT, PPT1 |
Description
The PPT1 gene encodes palmitoyl-protein thioesterase 1, a lysosomal enzyme that removes palmitate groups from cysteine residues of proteins. This depalmitoylation is essential for protein degradation and recycling. Mutations in PPT1 cause neuronal ceroid lipofuscinosis type 1 (CLN1), a severe neurodegenerative disorder. The enzyme is ubiquitously expressed but most critical in neurons, where its deficiency leads to accumulation of autofluorescent lipopigments and neuronal death.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuronal Ceroid Lipofuscinosis 1 (CLN1) | Loss-of-function mutations in PPT1 lead to deficient enzyme activity, causing accumulation of palmitoylated proteins and lipofuscin in lysosomes, leading to neurodegeneration. | ClinVar, OMIM |
| Infantile Neuronal Ceroid Lipofuscinosis (INCL) | Severe early-onset form of CLN1 due to complete loss of PPT1 activity, resulting in rapid psychomotor deterioration. | OMIM, NCBI |
| Adult Neuronal Ceroid Lipofuscinosis (Kufs disease, type A) | Milder, later-onset form caused by partial PPT1 deficiency, with slower progression and variable symptoms. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 20.1 | High |
| Testis | 15.3 | Medium |
| Kidney | 12.8 | Medium |
| Liver | 10.5 | Medium |
| Heart | 8.2 | Low |
| Lung | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.5 | High expression; used for neuronal studies |
| HepG2 (hepatocellular carcinoma) | 12.0 | Moderate expression |
| A549 (lung carcinoma) | 7.8 | Low expression |
| MCF7 (breast cancer) | 9.3 | Low to moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.451C>T (p.Arg151Ter) | Nonsense | ~30% of CLN1 alleles | Premature stop codon; loss of enzyme function |
| c.364A>G (p.Thr122Ala) | Missense | ~10% of CLN1 alleles | Reduced enzyme activity; misfolding |
| c.533A>G (p.Tyr178Cys) | Missense | ~5% of CLN1 alleles | Impaired catalytic activity |
| c.1A>G (p.Met1Val) | Start codon loss | Rare | No translation initiation; complete loss of protein |
Mutation functional classification
Loss of Function (LOF)
Most PPT1 mutations are loss-of-function, leading to reduced or absent enzyme activity. This results in lysosomal storage of palmitoylated proteins and lipofuscin, causing neurodegeneration.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PPT1.
Dominant Negative (DN)
No dominant-negative effects are known; PPT1 mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • palmitoyl hydrolase activity | • lysosome |
| • protein depalmitoylation | • lipid catabolic process |
| • neuron development |
Pathways
• Lysosomal degradation pathway
• Protein depalmitoylation
• Sphingolipid metabolism (indirect)
Protein Summary
Palmitoyl-protein thioesterase 1 (PPT1) is a 306-amino acid lysosomal enzyme that catalyzes the removal of palmitate groups from cysteine residues of proteins. It is synthesized as a preproprotein and processed to a mature form. PPT1 is involved in the degradation of lipid-modified proteins and plays a critical role in neuronal function. Deficiency leads to accumulation of autofluorescent storage material, particularly in neurons, causing progressive neurodegeneration. The protein is ubiquitously expressed, with highest levels in brain and testis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPT1 Knockout HEK293 Cell Line | EDJ-KQ17893 | Human | 5538 | Details Get a Quote |
| PPT1 Knockout A-549 Cell Line | EDJ-KQ22744 | Human | 5538 | Details Get a Quote |
| PPT1 Knockout HCT 116 Cell Line | EDJ-KQ22745 | Human | 5538 | Details Get a Quote |
| PPT1 Knockout HeLa Cell Line | EDJ-KQ22746 | Human | 5538 | Details Get a Quote |
| PPT1 Knockout Hep-G2 Cell Line | EDJ-KZ411 | Human | 5538 | Details Get a Quote |
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