Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

HSPB8

Reviewed January 2010

What is the official name of the HSPB8 gene?

The official name of this gene is “heat shock 22kDa protein 8.”

HSPB8 is the gene's official symbol. The HSPB8 gene is also known by other names, listed below.

What is the normal function of the HSPB8 gene?

The HSPB8 gene provides instructions for making a protein called heat shock protein beta-8 (also called heat shock protein 22). This protein is a member of the heat shock protein family, which helps protect cells under adverse conditions such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. Heat shock proteins block signals that lead to programmed cell death. In addition, they appear to be involved in activities such as cell movement (motility), stabilizing the cell's structural framework (the cytoskeleton), folding and stabilizing newly produced proteins, and repairing damaged proteins. Heat shock proteins also appear to play a role in the tensing of muscle fibers (muscle contraction).

Heat shock protein beta-8 is found in cells throughout the body and is particularly abundant in nerve cells. While its function is not well understood, it seems to interact with a related protein called heat shock protein beta-1, produced from the HSPB1 gene. In nerve cells, heat shock protein beta-1 helps to organize a network of molecular threads called neurofilaments that maintain the diameter of specialized extensions called axons. Maintaining proper axon diameter is essential for the efficient transmission of nerve impulses. The specific role that heat shock protein beta-8 plays in axons is unclear.

How are changes in the HSPB8 gene related to health conditions?

Charcot-Marie-Tooth disease - caused by mutations in the HSPB8 gene

A mutation in the HSPB8 gene has been reported in more than a dozen individuals in a large Chinese family with a form of Charcot-Marie-Tooth disease known as type 2L. Charcot-Marie-Tooth disease is a group of progressive disorders that affect the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.

The HSPB8 gene mutation that causes Charcot-Marie-Tooth disease changes the protein building block (amino acid) lysine to the amino acid asparagine at protein position 141, written as Lys141Asn or K141N.

It is unclear how HSPB8 gene mutations lead to the signs and symptoms of Charcot-Marie-Tooth disease, type 2L. Research suggests that the altered heat shock protein beta-8 interacts more strongly with heat shock protein beta-1 and is more likely to form clumps (aggregates). The aggregates may block the transport of substances that are essential for the proper function of nerve axons.

distal hereditary motor neuropathy, type II - caused by mutations in the HSPB8 gene

Researchers have identified at least two HSPB8 gene mutations that cause a condition called distal hereditary motor neuropathy, type II, which is similar to Charcot-Marie-Tooth disease. Distal hereditary motor neuropathy, type II affects peripheral nerves and is characterized by progressive weakness, primarily in the feet and legs. Unlike Charcot-Marie-Tooth disease, distal hereditary motor neuropathy, type II does not affect sensory cells.

One of the HSPB8 gene mutations that causes distal hereditary motor neuropathy, type II (Lys141Asn or K141N) is also associated with Charcot-Marie-Tooth disease, type 2L. Another mutation replaces the lysine in the same position with glutamic acid (written as Lys141Glu or K141E) and seems to increase protein aggregation in the same way. It is not well understood why the same HSPB8 gene mutation can cause either disorder. Researchers suggest that different distributions of protein aggregates within the peripheral nerves may result in different patterns of signs and symptoms. The disruption of other cell functions in which this protein is involved may also contribute to peripheral nerve disease.

Where is the HSPB8 gene located?

Cytogenetic Location: 12q24.23

Molecular Location on chromosome 12: base pairs 119,178,789 to 119,194,745

The HSPB8 gene is located on the long (q) arm of chromosome 12 at position 24.23.

The HSPB8 gene is located on the long (q) arm of chromosome 12 at position 24.23.

More precisely, the HSPB8 gene is located from base pair 119,178,789 to base pair 119,194,745 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about HSPB8?

You and your healthcare professional may find the following resources about HSPB8 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the HSPB8 gene or gene products?

  • CMT2L
  • DHMN2
  • E2IG1
  • E2-induced gene 1
  • H11
  • heat shock 27kDa protein 8
  • heat shock protein beta-8
  • HMN2
  • HMN2A
  • HSP22
  • HspB8
  • HSPB8_HUMAN
  • protein kinase H11
  • small stress protein-like protein HSP22

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding HSPB8?

amino acid ; asparagine ; axons ; cell ; contraction ; cytoskeleton ; diameter ; distal ; gene ; glutamic acid ; hereditary ; infection ; inflammation ; injury ; kinase ; lysine ; motor ; mutation ; neuropathy ; peripheral ; peripheral nerves ; protein ; sensory cells ; shock ; stress

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18325928?dopt=Abstract)
  • Fontaine JM, Rest JS, Welsh MJ, Benndorf R. The sperm outer dense fiber protein is the 10th member of the superfamily of mammalian small stress proteins. Cell Stress Chaperones. 2003 Spring;8(1):62-9. (http://www.ncbi.nlm.nih.gov/pubmed/12820655?dopt=Abstract)
  • 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. Epub 2006 Aug 25. (http://www.ncbi.nlm.nih.gov/pubmed/16935933?dopt=Abstract)
  • Gene Review: Charcot-Marie-Tooth Neuropathy Type 2 (http://www.ncbi.nlm.nih.gov/books/NBK1285)
  • OMIM: HEAT-SHOCK 22-KD PROTEIN 8 (http://omim.org/entry/608014)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17304582?dopt=Abstract)
  • 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. Epub 2004 May 2. (http://www.ncbi.nlm.nih.gov/pubmed/15122253?dopt=Abstract)
  • Kasakov AS, Bukach OV, Seit-Nebi AS, Marston SB, Gusev NB. Effect of mutations in the beta5-beta7 loop on the structure and properties of human small heat shock protein HSP22 (HspB8, H11). FEBS J. 2007 Nov;274(21):5628-42. Epub 2007 Oct 8. (http://www.ncbi.nlm.nih.gov/pubmed/17922839?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/26353)
  • Niemann A, Berger P, Suter U. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):217-42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16775378?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17722063?dopt=Abstract)
  • 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. Epub 2004 Nov 23. (http://www.ncbi.nlm.nih.gov/pubmed/15565283?dopt=Abstract)
  • Züchner S, Vance JM. Molecular genetics of autosomal-dominant axonal Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):63-74. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16775367?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2010
Published: April 13, 2015