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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
HSPB8
heat shock protein family B (small) member 8
Chromosome 12 Β· 12q24.23
NCBI Gene: 26353Ensembl: ENSG00000152137.8HGNC: HGNC:30171UniProt: Q9UJY1
143PubMed Papers
23Diseases
0Drugs
16Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein kinase activityprotein bindingidentical protein bindingprotein homodimerization activityCharcot-Marie-Tooth disease axonal type 2LAutosomal dominant Charcot-Marie-Tooth disease type 2Lmyopathy, myofibrillar, 13, with rimmed vacuolesdistal myopathy
✦AI Summary

HSPB8 (heat shock protein family B member 8) is a small chaperone protein that plays a crucial role in chaperone-assisted selective autophagy (CASA), a protein quality control mechanism particularly important in mechanically strained tissues like muscle 1. HSPB8 functions within a complex that includes HSPA, the cochaperone BAG3, and the E3 ubiquitin ligase STUB1 to promote selective degradation of misfolded and aggregating proteins 1. The protein exhibits temperature-dependent chaperone activity and is essential for maintaining cellular proteostasis under stress conditions 2. HSPB8 mutations cause several neuromuscular disorders including Charcot-Marie-Tooth disease type 2L, myofibrillar myopathy 13, and distal hereditary motor neuropathy type 2 34. Frameshift mutations in HSPB8 lead to protein aggregation that sequesters CASA components and autophagy receptors, resulting in impaired proteostasis and altered muscle cell differentiation 1. Beyond neuromuscular disorders, HSPB8 is involved in cancer biology, where it can have dual roles in tumor development and progression, and may contribute to chemoresistance 5. The protein's expression can be modulated by retinoic acid, which downregulates HSPB8 levels in breast cancer cells 6.

Sources cited
1
HSPB8's role in CASA complex, interaction with HSPA/BAG3/STUB1, and frameshift mutation effects
PMID: 36854646
2
HSPB8 upregulation in autophagy-related processes and TFEB-dependent manner
PMID: 30335591
3
HSPB8 gene association with distal hereditary motor neuropathies
PMID: 38702287
4
HSPB8 association with autosomal dominant distal myopathy
PMID: 33458580
5
HSPB8's dual role in cancer and involvement in chemoresistance
PMID: 33562660
6
Retinoic acid downregulation of HSPB8 in breast cancer cells
PMID: 34136389
Disease Associationsβ“˜23
Charcot-Marie-Tooth disease axonal type 2LOpen Targets
0.69Moderate
Autosomal dominant Charcot-Marie-Tooth disease type 2LOpen Targets
0.64Moderate
myopathy, myofibrillar, 13, with rimmed vacuolesOpen Targets
0.61Moderate
distal myopathyOpen Targets
0.44Moderate
neuronopathy, distal hereditary motor, autosomal dominantOpen Targets
0.37Weak
distal hereditary motor neuropathy type 2Open Targets
0.37Weak
myopathy, autophagic vacuolar, infantile-onsetOpen Targets
0.35Weak
genetic disorderOpen Targets
0.34Weak
male reproductive organ cancerOpen Targets
0.31Weak
dementiaOpen Targets
0.19Weak
Charcot-Marie-Tooth diseaseOpen Targets
0.16Weak
distal hereditary motor neuropathyOpen Targets
0.15Weak
Charcot-Marie-Tooth disease type 2Open Targets
0.15Weak
ovarian dysfunctionOpen Targets
0.14Weak
alcohol drinkingOpen Targets
0.11Weak
peripheral neuropathyOpen Targets
0.11Weak
melanomaOpen Targets
0.10Suggestive
intrahepatic cholangiocarcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
subarachnoid hemorrhageOpen Targets
0.07Suggestive
Charcot-Marie-Tooth disease, axonal, type 2LUniProt
Myopathy, myofibrillar, 13, with rimmed vacuolesUniProt
Neuronopathy, distal hereditary motor, autosomal dominant 2UniProt
Pathogenic Variants16
NM_014365.3(HSPB8):c.421A>G (p.Lys141Glu)Pathogenic
Neuronopathy, distal hereditary motor, type 2A|Charcot-Marie-Tooth disease axonal type 2L|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 141
NM_014365.3(HSPB8):c.562del (p.Gln188fs)Pathogenic
Neuronopathy, distal hereditary motor, type 2A|HSPB8-related neuromuscular disorder|Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜…β˜…β˜†β˜†2024β†’ Residue 188
NM_014365.3(HSPB8):c.508_509del (p.Gln170fs)Pathogenic
Charcot-Marie-Tooth disease axonal type 2L|Myopathy, autophagic vacuolar, infantile-onset|Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜…β˜…β˜†β˜†2024β†’ Residue 170
NM_014365.3(HSPB8):c.571del (p.Gln191fs)Pathogenic
Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜…β˜†β˜†β˜†2024β†’ Residue 191
NM_014365.3(HSPB8):c.423G>T (p.Lys141Asn)Pathogenic
Charcot-Marie-Tooth disease axonal type 2L|Charcot-Marie-Tooth disease|not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 141
NM_014365.3(HSPB8):c.508del (p.Gln170fs)Pathogenic
Charcot-Marie-Tooth disease axonal type 2L
β˜…β˜†β˜†β˜†2020β†’ Residue 170
NM_014365.3(HSPB8):c.419C>T (p.Thr140Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 140
NM_014365.3(HSPB8):c.520_533del (p.Tyr174fs)Likely pathogenic
Distal myopathy;
β˜…β˜†β˜†β˜†2017β†’ Residue 174
NM_014365.3(HSPB8):c.515dup (p.Pro173fs)Likely pathogenic
Inborn genetic diseases|Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜…β˜†β˜†β˜†2017β†’ Residue 173
NM_014365.3(HSPB8):c.413A>C (p.Asn138Thr)Likely pathogenic
Neuronopathy, distal hereditary motor, type 2A
β˜…β˜†β˜†β˜†2017β†’ Residue 138
NM_014365.3(HSPB8):c.422A>T (p.Lys141Met)Pathogenic
Charcot-Marie-Tooth disease axonal type 2L
β˜…β˜†β˜†β˜†2017β†’ Residue 141
NM_014365.3(HSPB8):c.538_542del (p.Ser180fs)Pathogenic
Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜…β˜†β˜†β˜†β†’ Residue 180
NM_014365.3(HSPB8):c.577_580dup (p.Thr194fs)Pathogenic
Charcot-Marie-Tooth disease axonal type 2L|Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜†β˜†β˜†β˜†2025β†’ Residue 194
NM_014365.3(HSPB8):c.525_529del (p.Thr176fs)Pathogenic
Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜†β˜†β˜†β˜†2025β†’ Residue 176
NM_014365.3(HSPB8):c.576_579delinsCAG (p.Glu192fs)Pathogenic
Myopathy, myofibrillar, 13, with rimmed vacuoles
β˜†β˜†β˜†β˜†2025β†’ Residue 192
NM_014365.3(HSPB8):c.423G>C (p.Lys141Asn)Pathogenic
Neuronopathy, distal hereditary motor, type 2A
β˜†β˜†β˜†β˜†2004β†’ Residue 141
View on ClinVar β†—
Related Genes
HSPA4Protein interaction99%HSPA8Protein interaction99%HSPB2Protein interaction99%DNAJB1Protein interaction99%HSPB3Protein interaction99%STUB1Protein interaction99%
Tissue Expression6 tissues
Heart
100%
Brain
19%
Lung
11%
Ovary
3%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
HSPB8HSPA4HSPA8HSPB2DNAJB1HSPB3STUB1
PROTEIN STRUCTURE
Preparing viewer…
PDB8S7A Β· 1.95 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.94LoF Tolerant
pLIβ“˜
0.05Tolerant
Observed/Expected LoF0.52 [0.31–0.94]
RankingsWhere HSPB8 stands among ~20K protein-coding genes
  • #3,197of 20,598
    Most Researched143 Β· top quartile
  • #2,388of 5,498
    Most Pathogenic Variants16
  • #8,796of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedHSPB8
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Distal hereditary motor neuropathies.
PMID: 38702287
Rev Neurol (Paris) Β· 2024
1.00
2
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration.
PMID: 30335591
Autophagy Β· 2019
0.90
3
Panorama of the distal myopathies.
PMID: 33458580
Acta Myol Β· 2020
0.80
4
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.70
5
Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.
PMID: 35302338
Eur J Transl Myol Β· 2022
0.60