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Genetics Home Reference: your guide to understanding genetic conditions
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TNFRSF11B

Reviewed February 2010

What is the official name of the TNFRSF11B gene?

The official name of this gene is “tumor necrosis factor receptor superfamily, member 11b.”

TNFRSF11B is the gene's official symbol. The TNFRSF11B gene is also known by other names, listed below.

What is the normal function of the TNFRSF11B gene?

The TNFRSF11B gene provides instructions for making a protein called osteoprotegerin. 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. Osteoprotegerin is involved in the regulation of specialized cells called osteoclasts, which break down bone tissue during bone remodeling.

Osteoprotegerin is one of two receptor proteins that can attach (bind) to a protein called receptor activator of NF-κB ligand (RANKL). The other receptor protein is called receptor activator of NF-κB (RANK). Because RANKL can only bind to one receptor at a time, osteoprotegerin and RANK compete with one another. When RANKL is bound to RANK, it sets off a series of chemical signals that trigger immature osteoclasts to mature and become fully functional. When RANKL is bound to osteoprotegerin, it blocks these chemical signals and prevents the activation of osteoclasts. Because no chemical signals are transmitted when RANKL is attached to osteoprotegerin, osteoprotegerin is often called a "decoy" receptor.

By reducing the amount of RANKL that is available to bind to RANK, osteoprotegerin plays a critical role in regulating the process of bone remodeling.

Does the TNFRSF11B gene share characteristics with other genes?

The TNFRSF11B gene belongs to a family of genes called TNFRSF (tumor necrosis factor receptor superfamily).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the TNFRSF11B gene related to health conditions?

juvenile Paget disease - caused by mutations in the TNFRSF11B gene

At least six mutations in the TNFRSF11B gene have been found to cause juvenile Paget disease. Each of these mutations greatly reduces the function of osteoprotegerin or prevents cells from making any of this protein. Without osteoprotegerin, RANKL binds only to RANK. The resulting increase in chemical signaling stimulates the production of too many osteoclasts and triggers these cells to break down bone abnormally. In people with juvenile Paget disease, 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 bones throughout the skeleton to become unusually large, misshapen, and easily broken (fractured).

Paget disease of bone - increased risk from variations of the TNFRSF11B gene

Studies suggest that several normal variations (polymorphisms) in the TNFRSF11B gene may increase the risk of developing classic Paget disease of bone, particularly in women. These genetic changes could affect the amount or function of osteoprotegerin. However, it is unclear how polymorphisms in this gene influence disease risk.

Where is the TNFRSF11B gene located?

Cytogenetic Location: 8q24

Molecular Location on chromosome 8: base pairs 118,923,556 to 118,952,143

The TNFRSF11B gene is located on the long (q) arm of chromosome 8 at position 24.

The TNFRSF11B gene is located on the long (q) arm of chromosome 8 at position 24.

More precisely, the TNFRSF11B gene is located from base pair 118,923,556 to base pair 118,952,143 on chromosome 8.

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 TNFRSF11B?

You and your healthcare professional may find the following resources about TNFRSF11B 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 TNFRSF11B gene or gene products?

  • MGC29565
  • OCIF
  • OPG
  • osteoclastogenesis inhibitory factor
  • osteoprotegerin
  • osteoprotegerin precursor
  • TR1
  • TR11B_HUMAN

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 TNFRSF11B?

bone remodeling ; gene ; juvenile ; ligand ; necrosis ; precursor ; protein ; receptor ; tissue ; tumor

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

References

  • Beyens G, Daroszewska A, de Freitas F, Fransen E, Vanhoenacker F, Verbruggen L, Zmierczak HG, Westhovens R, Van Offel J, Ralston SH, Devogelaer JP, Van Hul W. Identification of sex-specific associations between polymorphisms of the osteoprotegerin gene, TNFRSF11B, and Paget's disease of bone. J Bone Miner Res. 2007 Jul;22(7):1062-71. (http://www.ncbi.nlm.nih.gov/pubmed/17388729?dopt=Abstract)
  • Chong B, Hegde M, Fawkner M, Simonet S, Cassinelli H, Coker M, Kanis J, Seidel J, Tau C, Tüysüz B, Yüksel B, Love D; International Hyperphosphatasia Collaborative Group. Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between phenotype and genotype. J Bone Miner Res. 2003 Dec;18(12):2095-104. (http://www.ncbi.nlm.nih.gov/pubmed/14672344?dopt=Abstract)
  • Cundy T, Hegde M, Naot D, Chong B, King A, Wallace R, Mulley J, Love DR, Seidel J, Fawkner M, Banovic T, Callon KE, Grey AB, Reid IR, Middleton-Hardie CA, Cornish J. A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet. 2002 Sep 1;11(18):2119-27. (http://www.ncbi.nlm.nih.gov/pubmed/12189164?dopt=Abstract)
  • Daroszewska A, Hocking LJ, McGuigan FE, Langdahl B, Stone MD, Cundy T, Nicholson GC, Fraser WD, Ralston SH. Susceptibility to Paget's disease of bone is influenced by a common polymorphic variant of osteoprotegerin. J Bone Miner Res. 2004 Sep;19(9):1506-11. Epub 2004 Jun 14. (http://www.ncbi.nlm.nih.gov/pubmed/15312251?dopt=Abstract)
  • Janssens K, de Vernejoul MC, de Freitas F, Vanhoenacker F, Van Hul W. An intermediate form of juvenile Paget's disease caused by a truncating TNFRSF11B mutation. Bone. 2005 Mar;36(3):542-8. (http://www.ncbi.nlm.nih.gov/pubmed/15777670?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4982)
  • Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997 Apr 18;89(2):309-19. (http://www.ncbi.nlm.nih.gov/pubmed/9108485?dopt=Abstract)
  • Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH, Mumm S. Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J Med. 2002 Jul 18;347(3):175-84. (http://www.ncbi.nlm.nih.gov/pubmed/12124406?dopt=Abstract)
  • Wuyts W, Van Wesenbeeck L, Morales-Piga A, Ralston S, Hocking L, Vanhoenacker F, Westhovens R, Verbruggen L, Anderson D, Hughes A, Van Hul W. Evaluation of the role of RANK and OPG genes in Paget's disease of bone. Bone. 2001 Jan;28(1):104-7. (http://www.ncbi.nlm.nih.gov/pubmed/11165949?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: February 23, 2015