Encyclopedia
TNF receptor superfamily member 11b: The TNFRSF11B gene provides instructions for making a protein called osteoprotegerin.
- genes
1. 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.
2. Health Conditions Related to Genetic Changes
2.1. 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.
2.2. 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).
3. 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
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/tnfrsf11b
References
- Beyens G, Daroszewska A, de Freitas F, Fransen E, Vanhoenacker F, VerbruggenL, Zmierczak HG, Westhovens R, Van Offel J, Ralston SH, Devogelaer JP, Van Hul W.Identification of sex-specific associations between polymorphisms of theosteoprotegerin gene, TNFRSF11B, and Paget's disease of bone. J Bone Miner Res.2007 Jul;22(7):1062-71.
- Chong B, Hegde M, Fawkner M, Simonet S, Cassinelli H, Coker M, Kanis J, SeidelJ, Tau C, Tüysüz B, Yüksel B, Love D; International HyperphosphatasiaCollaborative Group. Idiopathic hyperphosphatasia and TNFRSF11B mutations:relationships between phenotype and genotype. J Bone Miner Res. 2003Dec;18(12):2095-104.
- 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 anidiopathic hyperphosphatasia phenotype. Hum Mol Genet. 2002 Sep 1;11(18):2119-27.
- 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 isinfluenced by a common polymorphic variant of osteoprotegerin. J Bone Miner Res. 2004 Sep;19(9):1506-11.
- Janssens K, de Vernejoul MC, de Freitas F, Vanhoenacker F, Van Hul W. Anintermediate form of juvenile Paget's disease caused by a truncating TNFRSF11Bmutation. Bone. 2005 Mar;36(3):542-8.
- 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 bonedensity. Cell. 1997 Apr 18;89(2):309-19.
- 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. 2002Jul 18;347(3):175-84.
- 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 therole of RANK and OPG genes in Paget's disease of bone. Bone. 2001Jan;28(1):104-7.
