TPP1 Gene: Tripeptidyl Peptidase 1
Genetic and Functional Insights into TPP1, a Key Lysosomal Serine Protease Associated with Neurodegenerative Disorders
Gene Information Card
| Symbol | TPP1 |
|---|---|
| Full Name | Tripeptidyl Peptidase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 1200 ncbi.nlm.nih.gov/gene/1200 |
| Ensembl ID | ENSG00000166340 |
| UniProt ID | O14773 |
| OMIM ID | 607998 |
| HGNC ID | 12009 |
| Aliases | CLN2, GIG1, LPIC, TPP-1 |
Description
The TPP1 gene encodes tripeptidyl peptidase 1, a lysosomal serine protease that cleaves N-terminal tripeptides from polypeptides. It is essential for protein degradation in lysosomes. Mutations in TPP1 cause classic late-infantile neuronal ceroid lipofuscinosis (CLN2 disease), a neurodegenerative lysosomal storage disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuronal Ceroid Lipofuscinosis 2 (CLN2 disease) | Loss-of-function mutations in TPP1 lead to deficient tripeptidyl peptidase 1 activity, causing accumulation of autofluorescent lipopigments in lysosomes, particularly in neurons. | ClinVar, OMIM |
| Spinocerebellar Ataxia 7 (SCA7) | Indirect: TPP1 dysfunction may contribute to proteotoxicity in polyglutamine disorders, but direct causal link not established. | NCBI Gene, PubMed |
| Epilepsy (symptomatic) | Secondary to neurodegeneration in CLN2 disease; not a primary genetic association. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Heart | 5.9 | Low |
| Lung | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression |
| SH-SY5Y | 9.8 | Neuronal model |
| HepG2 | 7.5 | Hepatocyte model |
| HeLa | 6.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.509-1G>C | Splice site | Common (founder mutation in CLN2) | Loss of function; leads to exon skipping and premature truncation |
| c.622C>T (p.Arg208*) | Nonsense | Rare | Premature stop codon; complete loss of enzyme activity |
| c.887G>A (p.Arg296Gln) | Missense | Rare | Reduced catalytic activity; partial loss of function |
| c.1340G>A (p.Arg447His) | Missense | Rare | Impaired protein stability and activity |
Mutation functional classification
Loss of Function (LOF)
Most TPP1 mutations (splice site, nonsense, missense) result in loss of enzymatic activity, leading to CLN2 disease.
Gain of Function (GOF)
No gain-of-function mutations reported for TPP1.
Dominant Negative (DN)
No dominant-negative mutations reported; TPP1 disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • tripeptidyl-peptidase activity | • serine-type peptidase activity |
| • lysosome | • proteolysis |
| • protein catabolic process | • lysosomal lumen |
Pathways
• Lysosome (KEGG hsa04142)
• Autophagy - animal (KEGG hsa04140)
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
Protein Summary
Tripeptidyl peptidase 1 (TPP1) is a 563-amino-acid lysosomal serine protease synthesized as a proenzyme and activated by autocatalytic cleavage. It removes N-terminal tripeptides from substrates, playing a critical role in lysosomal protein turnover. Deficiency leads to accumulation of storage material, particularly in neurons, causing progressive neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPP1 Knockout HEK293 Cell Line | EDJ-KQ4290 | Human | 1200 | Details Get a Quote |
| CSTPP1 Knockout HEK293 Cell Line | EDJ-KQ13020 | Human | 79096 | Details Get a Quote |
| TPP1 Knockout A-549 Cell Line | EDJ-KQ25475 | Human | 1200 | Details Get a Quote |
| TPP1 Knockout HCT 116 Cell Line | EDJ-KQ26775 | Human | 1200 | Details Get a Quote |
| TPP1 Knockout HeLa Cell Line | EDJ-KQ26776 | Human | 1200 | Details Get a Quote |
| CSTPP1 Knockout A-549 Cell Line | EDJ-KQ42285 | Human | 79096 | Details Get a Quote |
| CSTPP1 Knockout HCT 116 Cell Line | EDJ-KQ42286 | Human | 79096 | Details Get a Quote |
| CSTPP1 Knockout HeLa Cell Line | EDJ-KQ42287 | Human | 79096 | Details Get a Quote |
| DCTPP1 Knockout HEK293 Cell Line | EDJ-KQ51663 | Human | 79077 | Details Get a Quote |
| DCTPP1 Knockout HeLa Cell Line | EDJ-KQ57142 | Human | 79077 | Details Get a Quote |
| DCTPP1 Knockout A-549 Cell Line | EDJ-KQ65655 | Human | 79077 | Details Get a Quote |
| DCTPP1 Knockout HCT 116 Cell Line | EDJ-KQ74079 | Human | 79077 | Details Get a Quote |
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