PREPL (Prolyl Endopeptidase-Like) Gene
A comprehensive biomedical overview of the PREPL gene, its function, associated diseases, expression, and mutations.
Gene Information Card
| Symbol | PREPL |
|---|---|
| Full Name | prolyl endopeptidase-like |
| Gene Type | protein coding |
| Chromosomal Location | 2p21 |
| NCBI Gene ID | 9581 ncbi.nlm.nih.gov/gene/9581 |
| Ensembl ID | ENSG00000138073 |
| UniProt ID | Q6P1J9 |
| OMIM ID | 613558 |
| HGNC ID | 18302 |
| Aliases | FLJ12443, MGC126851, MGC126853 |
Description
PREPL (prolyl endopeptidase-like) is a protein-coding gene located on chromosome 2p21. It encodes a serine peptidase that belongs to the prolyl oligopeptidase family. PREPL is involved in various cellular processes, including protein processing, vesicle trafficking, and energy metabolism. Mutations in PREPL have been associated with congenital myasthenic syndrome and hypotonia-cystinuria syndrome. The gene is widely expressed in many tissues, with notable levels in the brain, kidney, and skeletal muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital myasthenic syndrome (CMS) | Loss-of-function mutations in PREPL lead to impaired synaptic vesicle recycling and reduced acetylcholine release at the neuromuscular junction, causing muscle weakness. | ClinVar, OMIM |
| Hypotonia-cystinuria syndrome (HCS) | Deletions or mutations affecting PREPL and adjacent genes (e.g., SLC3A1) result in hypotonia, cystinuria, and growth hormone deficiency. | OMIM, ClinVar |
| Myasthenic syndrome, congenital, 22 | Specific biallelic mutations in PREPL cause CMS type 22, characterized by neonatal hypotonia, feeding difficulties, and ptosis. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 17.2 | High |
| Kidney | 14.5 | High |
| Skeletal Muscle | 12.8 | High |
| Liver | 8.3 | Medium |
| Heart | 7.1 | Medium |
| Lung | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression |
| HeLa | 12.3 | Moderate expression |
| HepG2 | 9.8 | Moderate expression |
| A549 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1291C>T (p.Arg431Ter) | Nonsense | Rare | Loss of function; premature stop codon leading to truncated protein |
| c.1555G>A (p.Gly519Arg) | Missense | Rare | Loss of function; affects catalytic activity |
| c.1642del (p.Leu548TrpfsTer9) | Frameshift | Rare | Loss of function; frameshift leading to truncated protein |
| c.1A>G (p.Met1Val) | Start codon loss | Rare | Loss of function; prevents translation initiation |
Mutation functional classification
Loss of Function (LOF)
Most PREPL mutations are loss-of-function, leading to reduced or absent enzyme activity, causing CMS and HCS.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PREPL.
Dominant Negative (DN)
No dominant-negative mutations have been described; PREPL disorders are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • serine-type peptidase activity | • proteolysis |
| • peptidase activity | • cytoplasm |
| • extracellular exosome | • synaptic vesicle |
Pathways
• Protein processing in endoplasmic reticulum
• Neurotransmitter release cycle
• Metabolic pathways
Protein Summary
The PREPL protein is a 680-amino acid serine peptidase with a conserved catalytic triad (Ser, His, Asp). It is localized in the cytoplasm and associated with synaptic vesicles. PREPL is involved in the cleavage of peptide bonds, particularly after proline residues, and plays a role in vesicle trafficking and energy metabolism. It interacts with proteins such as SNAP25 and VAMP2, influencing neurotransmitter release. Mutations affecting its catalytic activity or stability lead to neuromuscular and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PREPL Knockout HEK293 Cell Line | EDJ-KQ6645 | Human | 9581 | Details Get a Quote |
| PREPL Knockout A-549 Cell Line | EDJ-KQ30921 | Human | 9581 | Details Get a Quote |
| PREPL Knockout HCT 116 Cell Line | EDJ-KQ30922 | Human | 9581 | Details Get a Quote |
| PREPL Knockout HeLa Cell Line | EDJ-KQ29570 | Human | 9581 | Details Get a Quote |
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