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

SOST gene

sclerostin

Normal Function

The SOST gene provides instructions for making the protein sclerostin. Sclerostin is produced in bone cells called osteocytes and plays an important role in bone formation.

Bone remodeling is a normal process in which old bone is broken down and new bone is formed. Bone remodeling is carefully controlled to ensure that bones stay strong and healthy. It requires a balance between the formation of new bone tissue and the breakdown and removal (resorption) of old bone tissue. The main function of sclerostin is to stop (inhibit) bone formation. Inhibiting bone formation helps to ensure that bones are the correct shape, size, and density.

Research suggests that sclerostin works by interfering with a process called Wnt signaling, which plays a key role in the regulation of bone formation. Sclerostin may also promote the self-destruction (apoptosis) of bone cells, further inhibiting bone growth.

Health Conditions Related to Genetic Changes

SOST-related sclerosing bone dysplasia

Genetic changes in or near the SOST gene can cause SOST-related sclerosing bone dysplasias, which are characterized by abnormal hardening (sclerosis) of the bone and increased bone formation (hyperostosis). As a result of hyperostosis, bones throughout the body may be wider and denser than normal, particularly the bones of the skull, lower jaw (mandible), arms, and legs. There are two forms of SOST-related sclerosing bone dysplasia: SOST-related sclerosteosis and van Buchem disease (also called SOST-related endosteal hyperostosis, van Buchem type). Although the features seen in people with van Buchem disease may overlap with those seen in people with SOST-related sclerosteosis, they tend to be less severe.

The changes in the SOST gene that cause SOST-related sclerosteosis are known as “loss-of-function variants” because they reduce the activity of sclerostin or decrease the amount of sclerostin that is produced by the cells. Some of the variants prevent the production of any functional sclerostin. This disrupts the ability to inhibit bone growth and causes the hyperostosis seen in affected individuals.

Changes in a region of DNA near the SOST gene cause van Buchem disease. The most common change in people with van Buchem disease is the deletion of a region of DNA that helps regulate the activity (expression) of the SOST gene. This decreases SOST gene expression and reduces protein production, which leads to a shortage of functional sclerostin protein. A shortage of sclerostin disrupts the protein's ability to inhibit bone growth, allowing the hyperostosis seen in people with van Buchem disease.

More About This Health Condition

Other disorders

Genetic changes in the SOST gene have also been found to cause SOST-related craniodiaphyseal dysplasia, an extremely rare condition that causes hyperostosis. However, people with SOST-related craniodiaphyseal dysplasia typically have more severe hyperostosis of the bones in the skull than people with SOST-related sclerosing bone dysplasias. In people with SOST-related craniodiaphyseal dysplasia, hyperostosis of the bones in the skull compress the nerves of the head and neck and increase the pressure on parts of the brain. Affected individuals may also have a narrowing of the nasal passages (choanal atresia), which can cause breathing problems. Because the signs and symptoms seen in people with SOST-related craniodiaphyseal dysplasia tend to be severe, affected individuals often do not survive past childhood. The changes in the SOST gene that are associated with craniodiaphyseal dysplasia cause cells to make a version of sclerostin that cannot inhibit bone growth, allowing excessive bone formation.

Other Names for This Gene

  • DAND6
  • sclerosteosis
  • sclerostin precursor
  • VBCH

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

  • Appelman-Dijkstra N, Van Lierop A, Papapoulos S. SOST-Related Sclerosing Bone Dysplasias. 2002 Jun 4 [updated 2024 Aug 1]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK587318/ Citation on PubMed
  • Balemans W, Van Hul W. Human genetics of SOST. J Musculoskelet Neuronal Interact. 2006 Oct-Dec;6(4):355-6. No abstract available. Citation on PubMed
  • Ekhzaimy AA, Alyusuf EY, Alswailem M, Alzahrani AS. A Novel Mutation in a Gene Causes Sclerosteosis in a Family of Mediterranean Origin. Medicina (Kaunas). 2022 Jan 28;58(2):202. doi: 10.3390/medicina58020202. Citation on PubMed
  • Kim SJ, Bieganski T, Sohn YB, Kozlowski K, Semenov M, Okamoto N, Kim CH, Ko AR, Ahn GH, Choi YL, Park SW, Ki CS, Kim OH, Nishimura G, Unger S, Superti-Furga A, Jin DK. Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia. Hum Genet. 2011 May;129(5):497-502. doi: 10.1007/s00439-011-0947-3. Epub 2011 Jan 9. Citation on PubMed
  • ten Dijke P, Krause C, de Gorter DJ, Lowik CW, van Bezooijen RL. Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am. 2008 Feb;90 Suppl 1:31-5. doi: 10.2106/JBJS.G.01183. Citation on PubMed
  • Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. Nosology of genetic skeletal disorders: 2023 revision. Am J Med Genet A. 2023 May;191(5):1164-1209. doi: 10.1002/ajmg.a.63132. Epub 2023 Feb 13. Citation on PubMed
  • van Bezooijen RL, ten Dijke P, Papapoulos SE, Lowik CW. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005 Jun;16(3):319-27. doi: 10.1016/j.cytogfr.2005.02.005. Citation on PubMed
  • van Lierop AH, Appelman-Dijkstra NM, Papapoulos SE. Sclerostin deficiency in humans. Bone. 2017 Mar;96:51-62. doi: 10.1016/j.bone.2016.10.010. Epub 2016 Oct 11. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.