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Genetics Home Reference: your guide to understanding genetic conditions
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SQSTM1

Reviewed February 2010

What is the official name of the SQSTM1 gene?

The official name of this gene is “sequestosome 1.”

SQSTM1 is the gene's official symbol. The SQSTM1 gene is also known by other names, listed below.

What is the normal function of the SQSTM1 gene?

The SQSTM1 gene provides instructions for making a protein called p62. This protein plays an important role in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it. The p62 protein helps regulate this process through its role in a chemical signaling pathway that promotes the formation of osteoclasts. Osteoclasts are specialized cells that break down bone tissue during bone remodeling.

Studies suggest that p62 may have other functions in addition to its role in bone remodeling. It may be involved in recycling worn-out cell parts and unneeded proteins (autophagy), the self-destruction of cells (apoptosis), and the body's immune responses and inflammatory reactions.

How are changes in the SQSTM1 gene related to health conditions?

Paget disease of bone - caused by mutations in the SQSTM1 gene

More than 20 mutations in the SQSTM1 gene have been found to cause Paget disease of bone. Many SQSTM1 gene mutations change single protein building blocks (amino acids) in the p62 protein. The most common mutation replaces the amino acid proline with the amino acid leucine at protein position 392 (written as Pro392Leu or P392L).

Through a mechanism that is not well understood, SQSTM1 gene mutations appear to overactivate the chemical signaling pathway that promotes osteoclast formation. The increased signaling stimulates the production of too many osteoclasts and triggers these cells to break down bone abnormally. In people with Paget disease of bone, affected bone is broken down and replaced much faster than usual. When the new bone tissue grows, it is weaker and less organized than normal bone. These problems with bone remodeling cause certain bones to become unusually large, misshapen, and easily broken (fractured). It is unclear why the disease affects some bones but not others.

Where is the SQSTM1 gene located?

Cytogenetic Location: 5q35

Molecular Location on chromosome 5: base pairs 179,806,387 to 179,838,077

The SQSTM1 gene is located on the long (q) arm of chromosome 5 at position 35.

The SQSTM1 gene is located on the long (q) arm of chromosome 5 at position 35.

More precisely, the SQSTM1 gene is located from base pair 179,806,387 to base pair 179,838,077 on chromosome 5.

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 SQSTM1?

You and your healthcare professional may find the following resources about SQSTM1 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 SQSTM1 gene or gene products?

  • A170
  • EBI3-associated protein p60
  • OSIL
  • oxidative stress induced like
  • p60
  • p62
  • p62B
  • PDB3
  • phosphotyrosine independent ligand for the Lck SH2 domain p62
  • SQSTM_HUMAN
  • ubiquitin-binding protein p62
  • ZIP3

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 SQSTM1?

acids ; amino acid ; apoptosis ; autophagy ; bone remodeling ; cell ; domain ; gene ; kb ; leucine ; ligand ; mutation ; osteoclast ; oxidative stress ; proline ; protein ; stress ; tissue ; ubiquitin

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

References

  • Cavey JR, Ralston SH, Hocking LJ, Sheppard PW, Ciani B, Searle MS, Layfield R. Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutations. J Bone Miner Res. 2005 Apr;20(4):619-24. Epub 2004 Dec 6. (http://www.ncbi.nlm.nih.gov/pubmed/15765181?dopt=Abstract)
  • Goode A, Layfield R. Recent advances in understanding the molecular basis of Paget disease of bone. J Clin Pathol. 2010 Mar;63(3):199-203. doi: 10.1136/jcp.2009.064428. Epub 2009 Oct 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19858527?dopt=Abstract)
  • Hocking LJ, Lucas GJ, Daroszewska A, Mangion J, Olavesen M, Cundy T, Nicholson GC, Ward L, Bennett ST, Wuyts W, Van Hul W, Ralston SH. Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease. Hum Mol Genet. 2002 Oct 15;11(22):2735-9. (http://www.ncbi.nlm.nih.gov/pubmed/12374763?dopt=Abstract)
  • Laurin N, Brown JP, Morissette J, Raymond V. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet. 2002 Jun;70(6):1582-8. Epub 2002 Apr 30. (http://www.ncbi.nlm.nih.gov/pubmed/11992264?dopt=Abstract)
  • Morissette J, Laurin N, Brown JP. Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget's disease of bone. J Bone Miner Res. 2006 Dec;21 Suppl 2:P38-44. (http://www.ncbi.nlm.nih.gov/pubmed/17229007?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8878)
  • Rea SL, Walsh JP, Ward L, Magno AL, Ward BK, Shaw B, Layfield R, Kent GN, Xu J, Ratajczak T. Sequestosome 1 mutations in Paget's disease of bone in Australia: prevalence, genotype/phenotype correlation, and a novel non-UBA domain mutation (P364S) associated with increased NF-kappaB signaling without loss of ubiquitin binding. J Bone Miner Res. 2009 Jul;24(7):1216-23. doi: 10.1359/jbmr.090214. (http://www.ncbi.nlm.nih.gov/pubmed/19257822?dopt=Abstract)
  • Vadlamudi RK, Joung I, Strominger JL, Shin J. p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins. J Biol Chem. 1996 Aug 23;271(34):20235-7. (http://www.ncbi.nlm.nih.gov/pubmed/8702753?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: February 2010
Published: October 27, 2014