LONP1
Lon Peptidase 1, Mitochondrial
Gene Information Card
| Symbol | LONP1 |
|---|---|
| Full Name | Lon Peptidase 1, Mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 9361 ncbi.nlm.nih.gov/gene/9361 |
| Ensembl ID | ENSG00000104884 |
| UniProt ID | P36776 |
| OMIM ID | 605490 |
| HGNC ID | 9479 |
| Aliases | LON, LONP, PRSS15, PIM1, hLON |
Description
LONP1 encodes the mitochondrial Lon protease, a key enzyme responsible for degrading misfolded, oxidized, or damaged proteins within the mitochondrial matrix. It also functions as a chaperone and binds mitochondrial DNA, playing a critical role in mitochondrial protein quality control, stress response, and genome maintenance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| CODAS syndrome | Loss-of-function mutations in LONP1 impair mitochondrial proteostasis, leading to multisystem developmental abnormalities including cerebral, ocular, dental, auricular, and skeletal defects. | OMIM #600373; ClinVar |
| Mitochondrial encephalopathy | Defective Lon protease activity results in accumulation of damaged proteins and mitochondrial dysfunction, contributing to neurological symptoms. | ClinVar; PubMed studies |
| Cancer (various) | Altered LONP1 expression influences tumor cell survival by modulating mitochondrial stress responses and apoptosis. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Heart | 10.8 | High |
| Kidney | 9.2 | Medium |
| Brain | 6.1 | Medium |
| Skeletal Muscle | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.5 | High expression |
| HepG2 | 9.8 | Medium expression |
| SH-SY5Y | 7.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1961G>A (p.Arg654His) | Missense | Rare | Reduced proteolytic activity; associated with CODAS syndrome |
| c.2146C>T (p.Arg716Trp) | Missense | Rare | Impaired ATPase activity; linked to mitochondrial disease |
| c.2389G>A (p.Gly797Arg) | Missense | Rare | Dominant-negative effect; causes severe CODAS phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense mutations that reduce or abolish proteolytic or ATPase activity, leading to impaired mitochondrial protein degradation.
Gain of Function (GOF)
Not well-documented; some variants may increase protease activity but are not clinically characterized.
Dominant Negative (DN)
Mutations such as p.Gly797Arg interfere with wild-type Lon protease function, exacerbating mitochondrial dysfunction.
View complete mutation data：
Gene Ontology (GO)
| • ATP-dependent peptidase activity | • mitochondrial matrix |
| • protein quality control | • chaperone binding |
| • mitochondrial DNA binding |
Pathways
• Mitochondrial protein degradation
• Unfolded protein response (UPRmt)
• Oxidative stress response
Protein Summary
The Lon protease (P36776) is a 959-amino acid mitochondrial matrix protein that forms a homo-oligomeric ring structure. It contains an N-terminal mitochondrial targeting signal, a central AAA+ ATPase domain, and a C-terminal proteolytic domain. It selectively degrades oxidized and misfolded proteins, regulates mitochondrial gene expression, and is essential for maintaining mitochondrial homeostasis.
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