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TNFRSF11B gene
URL of this page: https://medlineplus.gov/genetics/gene/tnfrsf11b/

TNFRSF11B gene

TNF receptor superfamily member 11b

Normal Function

The TNFRSF11B gene provides instructions for making a protein that plays an important role in bone remodeling, a normal process in which old bone is broken down and replaced by new bone. The TNFRSF11B protein is involved in the regulation of specialized cells called osteoclasts, which break down bone tissue during bone remodeling.

The TNFRSF11B protein belongs to a larger family of receptor proteins. Other proteins, called ligands, can fit into specific sites on receptor proteins like a key into a lock. Together, ligands and their receptors trigger signaling pathways that affect cell development and function. The TNFRSF11B protein works outside of the cell membrane.

The TNFRSF11B protein and a receptor protein called RANK can each attach to a ligand called RANKL. Because RANKL can only bind to one of these proteins at a time, the TNFRSF11B protein and RANK compete with one another. When RANKL is bound to RANK, a series of chemical signals cause osteoclasts to mature and turn on. This leads to the breakdown of bone. When RANKL is bound to the TNFRSF11B protein, these chemical signals are blocked. The TNFRSF11B protein is called a "decoy" receptor protein because no chemical signals are transmitted when RANKL is attached to this protein.

By influencing the amount of RANKL that is available to bind to RANK and activate osteoclasts, the TNFRSF11B protein plays a critical role in regulating the process of bone remodeling.

Health Conditions Related to Genetic Changes

Juvenile Paget disease

Variants (also called mutations) in the TNFRSF11B gene cause juvenile Paget disease. This disorder appears in infancy or childhood and causes bones throughout the body to be abnormally large, misshapen, and easily broken (fractured). The TNFRSF11B gene variants that cause juvenile Paget disease reduce the amount of functional TNFRSF11B protein. When functional TNFRSF11B proteins are not available, more RANKL binds to RANK. The resulting increase in chemical signaling causes osteoclasts to be overactive. As a result, bone is broken down and then replaced much faster than usual, and the new bone tissue is less organized and weaker than normal bone. These problems with bone remodeling cause bones throughout the skeleton to become unusually large, misshapen, and prone to fracture.

More About This Health Condition

Other Names for This Gene

  • OCIF
  • OPG
  • osteoclastogenesis inhibitory factor
  • TR1
  • 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

Gene and Variant Databases

References

  • Chong B, Hegde M, Fawkner M, Simonet S, Cassinelli H, Coker M, Kanis J, Seidel J, Tau C, Tuysuz B, Yuksel 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. doi: 10.1359/jbmr.2003.18.12.2095. 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. doi: 10.1093/hmg/11.18.2119. 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. doi: 10.1016/j.bone.2004.12.004. Citation on PubMed
  • Naot D, Choi A, Musson DS, Simsek Kiper PO, Utine GE, Boduroglu K, Peacock M, DiMeglio LA, Cundy T. Novel homozygous mutations in the osteoprotegerin gene TNFRSF11B in two unrelated patients with juvenile Paget's disease. Bone. 2014 Nov;68:6-10. doi: 10.1016/j.bone.2014.07.034. Epub 2014 Aug 6. Citation on PubMed
  • Ralston SH, Taylor JP. Rare Inherited forms of Paget's Disease and Related Syndromes. Calcif Tissue Int. 2019 May;104(5):501-516. doi: 10.1007/s00223-019-00520-5. Epub 2019 Feb 13. Citation on PubMed
  • Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy 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. doi: 10.1016/s0092-8674(00)80209-3. 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. doi: 10.1056/NEJMoa013096. 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. doi: 10.1016/s8756-3282(00)00411-7. Citation on PubMed

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