CLPP Gene: Structure, Function, and Associated Diseases
Comprehensive guide to the CLPP gene, its protein product, expression patterns, mutations, and clinical significance.
Gene Information Card
| Symbol | CLPP |
|---|---|
| Full Name | Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 8192 ncbi.nlm.nih.gov/gene/8192 |
| Ensembl ID | ENSG00000125656 |
| UniProt ID | Q16740 |
| OMIM ID | 601119 |
| HGNC ID | 2084 |
| Aliases | ClpP, MGC141912 |
Description
The CLPP gene encodes the proteolytic subunit of the mitochondrial caseinolytic protease (ClpP), a serine peptidase complex. This enzyme is essential for protein quality control within the mitochondrial matrix, degrading misfolded, damaged, or short-lived regulatory proteins. CLPP is highly conserved across species and plays a critical role in maintaining mitochondrial proteostasis, energy metabolism, and cellular stress responses. Mutations in CLPP are primarily associated with Perrault syndrome, a rare autosomal recessive disorder characterized by sensorineural hearing loss and ovarian dysgenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Perrault syndrome 3 | Biallelic pathogenic variants in CLPP lead to loss of proteolytic activity, impairing mitochondrial protein degradation and leading to mitochondrial dysfunction, particularly affecting tissues with high energy demands like the inner ear and ovaries. | OMIM (618129), ClinVar, PubMed |
| Hearing loss | Sensorineural hearing loss is a core feature of Perrault syndrome caused by CLPP mutations, likely due to the high metabolic demand and vulnerability of cochlear hair cells to mitochondrial dysfunction. | OMIM (618129), PubMed |
| Ovarian dysgenesis | Premature ovarian insufficiency is another hallmark of Perrault syndrome. CLPP deficiency disrupts ovarian follicle development and maintenance, likely through impaired mitochondrial function and increased apoptosis in granulosa cells. | OMIM (618129), PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 17.2 | High |
| Skeletal Muscle | 15.8 | High |
| Liver | 12.1 | Medium |
| Kidney | 11.5 | Medium |
| Brain | 8.3 | Medium |
| Lung | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 14.5 | High expression |
| HeLa (cervical cancer) | 12.3 | High expression |
| A549 (lung carcinoma) | 9.8 | Medium expression |
| MCF7 (breast cancer) | 8.1 | Medium expression |
| HepG2 (liver cancer) | 7.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.433C>T (p.Arg145Ter) | Nonsense | Rare | Premature stop codon leading to a truncated, non-functional protein and loss of proteolytic activity. |
| c.577C>T (p.Arg193Ter) | Nonsense | Rare | Premature stop codon resulting in a truncated protein, causing loss of function. |
| c.440T>C (p.Leu147Pro) | Missense | Rare | Amino acid substitution likely disrupting protein folding and catalytic activity. |
| c.199A>G (p.Thr67Ala) | Missense | Rare | Missense variant affecting a conserved residue, potentially impairing protein stability or function. |
Mutation functional classification
Loss of Function (LOF)
The majority of pathogenic CLPP mutations are loss-of-function, including nonsense, frameshift, and splice-site variants that lead to a non-functional or absent ClpP protein. This results in impaired mitochondrial protein degradation and is the primary mechanism for Perrault syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLPP in human disease. The enzyme's role is primarily degradative, and increased activity is not associated with known pathologies.
Dominant Negative (DN)
No dominant-negative effects have been described for CLPP mutations. The disease is inherited in an autosomal recessive pattern, requiring biallelic loss-of-function variants.
View complete mutation data：
Gene Ontology (GO)
| • Serine-type endopeptidase activity | • ATP-dependent peptidase activity |
| • Protein homodimerization activity | • Mitochondrial matrix |
| • Proteolysis | • Cellular response to stress |
| • Mitochondrial protein processing |
Pathways
• Mitochondrial protein degradation
• Protein quality control in mitochondria
• Cellular response to oxidative stress
Protein Summary
The CLPP protein (UniProt Q16740) is a 232-amino acid serine protease that forms a heptameric ring structure. It assembles with the ATP-dependent chaperone CLPX to form the active ClpXP complex. This complex recognizes and unfolds specific protein substrates, threading them into the central pore of ClpP for degradation. CLPP is localized in the mitochondrial matrix and is crucial for degrading misfolded proteins, regulating metabolic enzymes, and processing mitochondrial peptides. Its activity is essential for maintaining mitochondrial health, particularly in tissues with high energy demands.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLPP Knockout HEK293 Cell Line | EDJ-KQ1339 | Human | 8192 | Details Get a Quote |
| CLPP Knockout A-549 Cell Line | EDJ-KQ22095 | Human | 8192 | Details Get a Quote |
| CLPP Knockout HCT 116 Cell Line | EDJ-KQ22097 | Human | 8192 | Details Get a Quote |
| CLPP Knockout HeLa Cell Line | EDJ-KQ22098 | Human | 8192 | Details Get a Quote |
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