CLPB Gene (Caseinolytic Peptidase B Homolog)
Mitochondrial Chaperone and ATPase Involved in Protein Quality Control and Neurodevelopmental Disorders
Gene Information Card
| Symbol | CLPB |
|---|---|
| Full Name | Caseinolytic Peptidase B Homolog |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.4 |
| NCBI Gene ID | 81570 ncbi.nlm.nih.gov/gene/81570 |
| Ensembl ID | ENSG00000162129 |
| UniProt ID | Q9H078 |
| OMIM ID | 616254 |
| HGNC ID | 25264 |
| Aliases | HSP78, SKD3, CLP-B, MGC131938 |
Description
The CLPB gene encodes a mitochondrial ATP-dependent chaperone and peptidase belonging to the Clp/Hsp100 family. It is involved in protein quality control, mitochondrial protein homeostasis, and the disaggregation of misfolded proteins. Mutations in CLPB cause 3-methylglutaconic aciduria type VII (MGCA7), characterized by cataracts, neutropenia, and neurodevelopmental delay.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 3-Methylglutaconic Aciduria Type VII (MGCA7) | Loss of CLPB chaperone function leads to impaired mitochondrial protein disaggregation, accumulation of damaged proteins, and mitochondrial dysfunction. | OMIM #616271; ClinVar |
| Cataracts (congenital) | CLPB deficiency disrupts lens protein homeostasis, causing protein aggregation and cataract formation. | OMIM #616254; PubMed studies |
| Neutropenia (severe congenital) | Mitochondrial stress in hematopoietic stem cells due to CLPB loss impairs neutrophil maturation and survival. | ClinVar; PubMed case reports |
| Neurodevelopmental Disorder with Hypotonia and Seizures | Impaired mitochondrial proteostasis in neurons leads to energy deficit and synaptic dysfunction. | OMIM #616271 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Low |
| Heart | 15.1 | Medium |
| Liver | 9.2 | Low |
| Skeletal Muscle | 18.5 | Medium |
| Testis | 22.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 14.6 | Myeloid lineage |
| HeLa (cervical) | 11.2 | Epithelial |
| HepG2 (liver) | 9.8 | Hepatocellular |
| SH-SY5Y (neuroblastoma) | 7.3 | Neuronal |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1522C>T (p.Arg508Trp) | Missense | Rare | Loss of ATPase activity; dominant negative effect |
| c.1129G>A (p.Gly377Arg) | Missense | Rare | Impaired substrate binding; reduced chaperone function |
| c.1876_1877del (p.Leu626Glufs*2) | Frameshift | Rare | Complete loss of function; severe MGCA7 phenotype |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein translation; null allele |
Mutation functional classification
Loss of Function (LOF)
Most CLPB mutations (frameshift, nonsense, start loss) lead to complete loss of chaperone activity, causing severe MGCA7 with neutropenia and cataracts.
Gain of Function (GOF)
No gain-of-function mutations reported for CLPB.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg508Trp) can exert dominant negative effects by forming non-functional oligomers, impairing wild-type CLPB activity.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • ATP hydrolysis activity (GO:0016887) |
| • Chaperone binding (GO:0051087) | • Protein disaggregation (GO:0051085) |
| • Mitochondrion (GO:0005739) | • Mitochondrial matrix (GO:0005759) |
| • Response to stress (GO:0006950) | • Protein folding (GO:0006457) |
Pathways
• Mitochondrial protein import and quality control
• Clp family chaperone system
• Protein disaggregation in mitochondria
Protein Summary
CLPB is a 789-amino acid mitochondrial protein with an N-terminal mitochondrial targeting sequence, a central AAA+ ATPase domain, and a C-terminal ClpB-like domain. It forms hexameric rings that use ATP hydrolysis to disaggregate and refold misfolded proteins in the mitochondrial matrix. CLPB is essential for maintaining mitochondrial proteostasis under stress conditions. Deficiency leads to protein aggregation, mitochondrial dysfunction, and tissue-specific pathologies in lens, bone marrow, and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLPB Knockout HEK293 Cell Line | EDJ-KQ2381 | Human | 81570 | Details Get a Quote |
| CLPB Knockout A-549 Cell Line | EDJ-KQ22854 | Human | 81570 | Details Get a Quote |
| CLPB Knockout HCT 116 Cell Line | EDJ-KQ22855 | Human | 81570 | Details Get a Quote |
| CLPB Knockout HeLa Cell Line | EDJ-KQ22856 | Human | 81570 | Details Get a Quote |
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