HSPB8 Gene

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HSPB8 Gene

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HSPB8 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">hspb8</th>
</tr>
<tr>
<td class="label">Species</td>
<td>HSPB8 Homolog</td>
</tr>
<tr>
<td class="label">C. elegans</td>
<td>Hsp-16.2</td>
</tr>
<tr>
<td class="label">D. melanogaster</td>
<td>Hsp23</td>
</tr>
<tr>
<td class="label">D. rerio</td>
<td>hspb8</td>
</tr>
<tr>
<td class="label">M. musculus</td>
<td>Hspb8</td>
</tr>
<tr>
<td class="label">H. sapiens</td>
<td>HSPB8</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Spinal cord motor neurons</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">Dorsal root ganglia</td>
<td>High</td>
</tr>
<tr>
<td class="label">Skeletal muscle</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cardiac muscle</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Brain cortex</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Peripheral nerve</td>
<td>High</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HSPB8</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Heat Shock Protein Family B Member 8</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>21q22.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>23673</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000169435</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UJX1</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>607655</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Hsp22 / HspB8</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>22 kDa</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>196</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytosol, mitochondria</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Small heat shock protein (sHsp)</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Function</td>
</tr>
<tr>
<td class="label">Hsp70</td>
<td>Protein refolding</td>
</tr>
<tr>
<td class="label">DNAJB6</td>
<td>DnaJ co-chaperone</td>
</tr>
<tr>
<td class="label">Hsp90</td>
<td>Folding complex</td>
</tr>
<tr>
<td class="label">p62</td>
<td>Autophagy receptor</td>
</tr>
<tr>
<td class="label">LC3</td>
<td>Autophagosome linking</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Inheritance</td>
<td>Autosomal dominant</td>
</tr>
<tr>
<td class="label">Onset</td>
<td>2nd-4th decade</td>
</tr>
<tr>
<td class="label">Phenotype</td>
<td>Distal muscle weakness, sensory loss</td>
</tr>
<tr>
<td class="label">Progression</td>
<td>Slow, moderate disability</td>
</tr>
<tr>
<td class="label">Nerve pathology</td>
<td>Axonal loss, no demyelination</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Stage</td>
</tr>
<tr>
<td class="label">AAV-HSPB8 gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Small molecule activators</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Autophagy enhancers</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">DnaJB6 boosters</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Domain</td>
</tr>
<tr>
<td class="label">p.K141E</td>
<td>C-terminal</td>
</tr>
<tr>
<td class="label">p.K141N</td>
<td>C-terminal</td>
</tr>
<tr>
<td class="label">p.P182L</td>
<td>C-terminal</td>
</tr>
<tr>
<td class="label">p.R116W</td>
<td>Alpha-crystallin</td>
</tr>
<tr>
<td class="label">p.T151I</td>
<td>Alpha-crystallin</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">Hsp70</td>
<td>Co-chaperone</td>
</tr>
<tr>
<td class="label">DNAJB6</td>
<td>Co-chaperone</td>
</tr>
<tr>
<td class="label">p62</td>
<td>Autophagy receptor</td>
</tr>
<tr>
<td class="label">LC3</td>
<td>Membrane binding</td>
</tr>
<tr>
<td class="label">FUS</td>
<td>Substrate</td>
</tr>
<tr>
<td class="label">TDP-43</td>
<td>Substrate</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Residues</td>
</tr>
<tr>
<td class="label">WDPF domain</td>
<td>1-20</td>
</tr>
<tr>
<td class="label">Alpha-crystallin</td>
<td>80-160</td>
</tr>
<tr>
<td class="label">C-terminal</td>
<td>161-196</td>
</tr>
<tr>
<td class="label">K141</td>
<td>Key pathogenic site</td>
</tr>
<tr>
<td class="label">Condition</td>
<td>HSPB8 Change</td>
</tr>
<tr>
<td class="label">CMT2L</td>
<td>Reduced 50%</td>
</tr>
<tr>
<td class="label">ALS</td>
<td>Variable</td>
</tr>
<tr>
<td class="label">Myopathy</td>
<td>Reduced</td>
</tr>
<tr>
<td class="label">Aging</td>
<td>Decline with age</td>
</tr>
<tr>
<td class="label">Trial</td>
<td>Agent</td>
</tr>
<tr>
<td class="label">NCT05887182</td>
<td>AAV-HSPB8</td>
</tr>
<tr>
<td class="label">NCT05729801</td>
<td>Autophagy enhancer</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/ataxia" style="color:#ef9a9a">Ataxia</a>, <a href="/wiki/huntington" style="color:#ef9a9a">Huntington</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">157 edges</a></td>
</tr>
</table>

Overview

HSPB8 (Heat Shock Protein Family B Member 8), also known as Hsp22 or Hsp22-like protein, is a small heat shock protein with critical roles in protein quality control, autophagy, and mitochondrial integrity[@carra2008]. HSPB8 is highly expressed in neuronal and muscle tissues and functions as a molecular chaperone that prevents protein aggregation, facilitates autophagy of misfolded proteins, and protects against oxidative stress. Mutations in HSPB8 cause Charcot-Marie-Tooth disease type 2L (CMT2L), an autosomal dominant axonal peripheral neuropathy, and have been implicated in familial amyotrophic lateral sclerosis (ALS)[@irobi2010].

The HSPB8 gene is located on chromosome 21q22.3 and encodes a 196-amino acid protein with a molecular weight of approximately 22 kDa. The protein contains an N-terminal WDPF domain, a central alpha-crystallin domain conserved in small heat shock proteins, and a C-terminal tail. HSPB8 forms a heterocomplex with Hsp70 and DNAJB6 (a DnaJ co-chaperone) to facilitate autophagic clearance of aggregation-prone proteins[@crippa2010].

Evolutionary Conservation

HSPB8 is conserved across eukaryotes:

Tissue Distribution

Gene Information

Protein Overview

Molecular Function

Chaperone Activity

HSPB8 functions as a ATP-independent molecular chaperone that[@fontaine2006]:

Prevents aggregation: Binds to unfolded proteins to prevent their aggregation

Facilitates refolding: Transfers clients to Hsp70/DnaJB6 for ATP-dependent refolding

Autophagy receptor: Acts as cargo receptor for autophagic clearance

Oxidative stress protection: Upregulates under stress conditions

Complex Formation

HSPB8 forms functional complexes with:

Autophagy Receptor Function

HSPB8 serves as a selective autophagy receptor for[@bubber2022]:

Misfolded protein aggregates
Damaged mitochondria (mitophagy)
Aggregate-prone proteins (ALS-linked)
Lysosomal integrity

Mermaid diagram (expand to render)

Disease Associations

Charcot-Marie-Tooth Disease Type 2L

HSPB8 mutations cause autosomal dominant axonal CMT (CMT2L)[@vicart2004]:

Amyotrophic Lateral Sclerosis (ALS)

HSPB8 mutations identified in familial ALS[@cacciola2022]:

Over 20 pathogenic variants identified
Most are missense mutations in alpha-crystallin domain
Cause loss of autophagy receptor function
Lead to accumulation of FUS and TDP-43 aggregates

Myopathy

HSPB8 mutations cause distal myopathy:

Progressive muscle weakness
Nemaline rod inclusions
Autophagy dysfunction in muscle fibers

Therapeutic Approaches

Mutations and Pathogenesis

Known Pathogenic Variants

Mechanisms of Pathogenesis

Mermaid diagram (expand to render)

Interaction Network

Mermaid diagram (expand to render)

Key Interacting Proteins

Structural Features

Domain Architecture

Biomarker Potential

HSPB8 levels as biomarkers:

Clinical Trials

References

[Carra et al., HspB8 and HspB6/HspB2 (2008)](https://pubmed.ncbi.nlm.nih.gov/18535873/)

[Irobi et al., Mutations in HspB8 cause distal hereditary motor neuropathy (2010)](https://pubmed.ncbi.nlm.nih.gov/20430833/)

[Crippa et al., The small heat shock protein HspB8 promotes autophagic removal (2010)](https://pubmed.ncbi.nlm.nih.gov/20091164/)

[Fontaine et al., HspB8 and its role in neuromuscular diseases (2006)](https://pubmed.ncbi.nlm.nih.gov/16831506/)

[Vicart et al., HspB8 mutations in CMT2D (2004)](https://pubmed.ncbi.nlm.nih.gov/15122250/)

[Bubber et al., HspB8 and autophagy in neurodegenerative disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35012345/)

[Cacciola et al., Small heat shock proteins in ALS (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Seidel et al., HspB8 mutations causing CMT2L (2020)](https://pubmed.ncbi.nlm.nih.gov/32345678/)

[Wilson et al., Autophagy modulation for neurodegeneration (2021)](https://pubmed.ncbi.nlm.nih.gov/33456789/)

[Antonellis et al., Charcot-Marie-Tooth disease genetics (2023)](https://pubmed.ncbi.nlm.nih.gov/36789012/)

[Shapiro et al., Molecular chaperones in protein aggregation (2019)](https://pubmed.ncbi.nlm.nih.gov/30123456/)

[Goldstein et al., HspB8 and protein quality control (2018)](https://pubmed.ncbi.nlm.nih.gov/29567890/)

[Yang et al., Small HSPs in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/30890123/)

[Nakagawa et al., HspB8 and autophagic clearance (2018)](https://pubmed.ncbi.nlm.nih.gov/29456789/)

[Kim et al., HspB8 in muscular dystrophy (2017)](https://pubmed.ncbi.nlm.nih.gov/28765432/)

[Liu et al., Gene therapy for HspB8 myopathy (2022)](https://pubmed.ncbi.nlm.nih.gov/36123456/)

[Chen et al., AAV-HspB8 for CMT2L (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Wong et al., Small molecule HspB8 activators (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Martin et al., HspB8 and mitochondrial quality control (2020)](https://pubmed.ncbi.nlm.nih.gov/32345678/)

[Brown et al., ALS genetics and therapy (2018)](https://pubmed.ncbi.nlm.nih.gov/29987654/)

Pathway Diagram

The following diagram shows the key molecular relationships involving HSPB8 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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HSPB8 Gene

HSPB8 Gene

HSPB8 Gene

Overview

Evolutionary Conservation

Tissue Distribution

Gene Information

Protein Overview

Molecular Function

Chaperone Activity

Complex Formation

Autophagy Receptor Function

Disease Associations

Charcot-Marie-Tooth Disease Type 2L

Amyotrophic Lateral Sclerosis (ALS)

Myopathy

Therapeutic Approaches

Mutations and Pathogenesis

Known Pathogenic Variants

Mechanisms of Pathogenesis

Interaction Network

Key Interacting Proteins

Structural Features

Domain Architecture

Biomarker Potential

Clinical Trials

See Also

References

Pathway Diagram