HSPB8: Small Heat Shock Protein B8
A molecular chaperone implicated in neuroprotection and cancer
Gene Information Card
| Symbol | HSPB8 |
|---|---|
| Full Name | Heat Shock Protein Family B (Small) Member 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.23 |
| NCBI Gene ID | 26353 ncbi.nlm.nih.gov/gene/26353 |
| Ensembl ID | ENSG00000152137 |
| UniProt ID | Q9UJY1 |
| OMIM ID | 608014 |
| HGNC ID | 30171 |
| Aliases | HSP22, HMN2, CMT2L, DHMN2, E2IG1, HMN2A |
Description
HSPB8 (Heat Shock Protein Family B (Small) Member 8) encodes a 22 kDa small heat shock protein (sHSP) that functions as a molecular chaperone. It is involved in protein quality control, autophagy, and protection against cellular stress. Mutations in HSPB8 are associated with Charcot-Marie-Tooth disease type 2L (CMT2L) and distal hereditary motor neuropathy type II (dHMN2). The protein interacts with BAG3 to facilitate selective autophagy of misfolded proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2L (CMT2L) | Missense mutations (e.g., K141N, K141E) impair chaperone function and promote protein aggregation, leading to axonal degeneration. | ClinVar, OMIM |
| Distal hereditary motor neuropathy type II (dHMN2) | Same mutations disrupt BAG3-mediated autophagy, causing accumulation of damaged proteins in motor neurons. | OMIM, PubMed |
| Amyotrophic lateral sclerosis (ALS) susceptibility | Rare variants may contribute to motor neuron vulnerability through impaired proteostasis. | ClinVar, literature |
| Breast cancer | Overexpression of HSPB8 correlates with poor prognosis; may promote tumor cell survival under stress. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 22.5 | Medium |
| Heart | 18.3 | Medium |
| Brain | 12.1 | Medium |
| Liver | 8.4 | Low |
| Kidney | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HeLa (cervical carcinoma) | 10.8 | Epithelial |
| MCF7 (breast cancer) | 9.5 | Hormone-responsive |
| HepG2 (hepatocellular carcinoma) | 6.3 | Liver-derived |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| K141N | Missense | Rare | Impairs chaperone activity; associated with CMT2L/dHMN2 |
| K141E | Missense | Rare | Similar to K141N; disrupts BAG3 binding |
| P182L | Missense | Rare | Reported in dHMN2; reduces solubility |
| R7W | Missense | Rare | Uncertain significance; possibly benign |
Mutation functional classification
Loss of Function (LOF)
K141N and K141E reduce chaperone activity and impair autophagy-mediated clearance of misfolded proteins.
Gain of Function (GOF)
Not clearly established; some mutants may promote toxic aggregation.
Dominant Negative (DN)
Mutant HSPB8 interferes with wild-type protein function in oligomeric complexes.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005212 - structural constituent of eye lens | • GO:0051082 - unfolded protein binding |
| • GO:0006457 - protein folding | • GO:0031625 - ubiquitin protein ligase binding |
| • GO:0042802 - identical protein binding | • GO:0005737 - cytoplasm |
| • GO:0005829 - cytosol | • GO:0032991 - protein-containing complex |
Pathways
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
• Autophagy - animal (KEGG hsa04140)
• Chaperone-mediated autophagy (Reactome R-HSA-9613829)
Protein Summary
HSPB8 is a 196-amino-acid small heat shock protein that forms oligomeric complexes and functions as a molecular chaperone. It binds to BAG3 and HSP70 to target misfolded proteins for selective autophagy. The protein is highly expressed in muscle and neuronal tissues. Pathogenic mutations cluster in the alpha-crystallin domain and impair its protective functions, leading to motor neuron degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HSPB8 Knockout HEK293 Cell Line | EDJ-KQ2284 | Human | 26353 | Details Get a Quote |
| HSPB8 Knockout A-549 Cell Line | EDJ-KQ22633 | Human | 26353 | Details Get a Quote |
| HSPB8 Knockout HCT 116 Cell Line | EDJ-KQ22634 | Human | 26353 | Details Get a Quote |
| HSPB8 Knockout HeLa Cell Line | EDC09860 | Human | 26353 | Details Get a Quote |
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