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URL of this page: https://medlineplus.gov/genetics/gene/hspb8/

HSPB8 gene

heat shock protein family B (small) member 8

Normal Function

The HSPB8 gene provides instructions for making a protein called heat shock protein beta-8. This protein is a member of the heat shock protein family, which helps protect cells that are under stress from factors such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. Heat shock proteins block signals that lead cells to self-destruct (undergo apoptosis). In addition, they appear to be involved in cell movement, stabilizing the cell's structural framework (the cytoskeleton), folding and stabilizing newly produced proteins, and repairing damaged proteins. Heat shock proteins also seem to play a role in the tensing of muscle fibers (muscle contraction).

Heat shock protein beta-8 is found in cells throughout the body, where it helps fold newly produced proteins and refold damaged proteins. Heat shock protein beta-8 seems to interact with a related protein called heat shock protein beta-1, which is produced from the HSPB1 gene. In nerve cells (neurons), heat shock protein beta-1 helps to organize a network of molecular threads called neurofilaments that maintain the structure of a part of the neuron called the axon. This allows neurons to transmit nerve impulses efficiently. The specific role that heat shock protein beta-8 plays in axons is unclear.

Health Conditions Related to Genetic Changes

Distal hereditary motor neuropathy, type II

Variants (also called mutations) in the HSPB8 gene have been found to cause a condition called distal hereditary motor neuropathy, type II. This condition is characterized by damage to specialized neurons in the brain and spinal cord that control muscle movement (motor neurons). Damage to motor neurons leads to progressive weakness and loss of muscle tissue (atrophy) in the feet and legs.

Research suggests that HSPB8 gene variants cause cells to produce an altered version of heat shock protein beta-8 that interacts more strongly with heat shock protein beta-1 and is more likely to form clusters (aggregates). These aggregates can build up and impair the function of cells, particularly motor neurons. In addition, motor neurons that do not have a functional version of heat shock protein beta-8 are vulnerable to stress and cell damage. As a result, these cells are more likely to die off over time, leading to the signs and symptoms of distal hereditary motor neuropathy, type II.

More About This Health Condition

Charcot-Marie-Tooth disease

MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease

More About This Health Condition

Other Names for This Gene

  • H11
  • heat shock protein beta-8
  • HSP22
  • HspB8
  • HSPB8_HUMAN
  • protein kinase H11

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bird TD. Charcot-Marie-Tooth Hereditary Neuropathy Overview. 1998 Sep 28 [updated 2025 Jan 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1358/ Citation on PubMed
  • Datskevich PN, Nefedova VV, Sudnitsyna MV, Gusev NB. Mutations of small heat shock proteins and human congenital diseases. Biochemistry (Mosc). 2012 Dec;77(13):1500-14. doi: 10.1134/S0006297912130081. Citation on PubMed
  • Dierick I, Baets J, Irobi J, Jacobs A, De Vriendt E, Deconinck T, Merlini L, Van den Bergh P, Rasic VM, Robberecht W, Fischer D, Morales RJ, Mitrovic Z, Seeman P, Mazanec R, Kochanski A, Jordanova A, Auer-Grumbach M, Helderman-van den Enden AT, Wokke JH, Nelis E, De Jonghe P, Timmerman V. Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study. Brain. 2008 May;131(Pt 5):1217-27. doi: 10.1093/brain/awn029. Epub 2008 Mar 5. Citation on PubMed
  • Drew AP, Blair IP, Nicholson GA. Molecular genetics and mechanisms of disease in distal hereditary motor neuropathies: insights directing future genetic studies. Curr Mol Med. 2011 Nov;11(8):650-65. doi: 10.2174/156652411797536714. Citation on PubMed
  • Fontaine JM, Sun X, Hoppe AD, Simon S, Vicart P, Welsh MJ, Benndorf R. Abnormal small heat shock protein interactions involving neuropathy-associated HSP22 (HSPB8) mutants. FASEB J. 2006 Oct;20(12):2168-70. doi: 10.1096/fj.06-5911fje. Epub 2006 Aug 25. Citation on PubMed
  • Hu Z, Chen L, Zhang J, Li T, Tang J, Xu N, Wang X. Structure, function, property, and role in neurologic diseases and other diseases of the sHsp22. J Neurosci Res. 2007 Aug 1;85(10):2071-9. doi: 10.1002/jnr.21231. Citation on PubMed
  • Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kremensky I, Van Den Bosch L, Robberecht W, Van Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, Timmerman V. Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. Nat Genet. 2004 Jun;36(6):597-601. doi: 10.1038/ng1328. Epub 2004 May 2. Citation on PubMed
  • Nefedova VV, Muranova LK, Sudnitsyna MV, Ryzhavskaya AS, Gusev NB. Small Heat Shock Proteins and Distal Hereditary Neuropathies. Biochemistry (Mosc). 2015 Dec;80(13):1734-47. doi: 10.1134/S000629791513009X. Citation on PubMed
  • Shemetov AA, Seit-Nebi AS, Gusev NB. Structure, properties, and functions of the human small heat-shock protein HSP22 (HspB8, H11, E2IG1): a critical review. J Neurosci Res. 2008 Feb 1;86(2):264-9. doi: 10.1002/jnr.21441. Citation on PubMed
  • Tang BS, Zhao GH, Luo W, Xia K, Cai F, Pan Q, Zhang RX, Zhang FF, Liu XM, Chen B, Zhang C, Shen L, Jiang H, Long ZG, Dai HP. Small heat-shock protein 22 mutated in autosomal dominant Charcot-Marie-Tooth disease type 2L. Hum Genet. 2005 Feb;116(3):222-4. doi: 10.1007/s00439-004-1218-3. Epub 2004 Nov 23. Citation on PubMed

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