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TNFRSF11B gene

TNF receptor superfamily member 11b
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Normal Function

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.

Health Conditions Related to Genetic Changes

Paget disease of bone

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.

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Juvenile Paget disease

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).

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Other Names for This Gene

  • MGC29565
  • OCIF
  • OPG
  • osteoclastogenesis inhibitory factor
  • osteoprotegerin
  • osteoprotegerin precursor
  • TR1
  • TR11B_HUMAN
  • tumor necrosis factor receptor superfamily member 11b
  • tumor necrosis factor receptor superfamily, member 11b

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
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