The SBDS gene provides instructions for making a protein that is critical for building ribosomes. Ribosomes are cellular structures that process the cell's genetic instructions to create proteins. Each ribosome is made up of two parts (subunits) called the large subunit and the small subunit. The SBDS protein helps prepare the large subunit so it can assemble into the ribosome by helping remove another protein (called eIF6) that blocks the interaction of the large subunit with the small subunit.
Research suggests that the SBDS protein may be involved in other cellular processes, such as ensuring proper cell division, aiding cell movement, protecting cells from stress, and processing RNA, a molecule that is a chemical cousin of DNA. More research is needed to clarify the protein's role in these processes.
Health Conditions Related to Genetic Changes
More than 80 mutations in the SBDS gene have been identified in people with Shwachman-Diamond syndrome. This condition causes problems related to impaired function of the bone marrow and pancreas. Affected individuals also have skeletal abnormalities and a higher-than-average chance of developing a blood cell cancer called acute myeloid leukemia or a related bone marrow disorder called myelodysplastic syndrome.
Many of the SBDS gene mutations involved in Shwachman-Diamond syndrome result from an exchange of genetic material between the SBDS gene and a very similar, but nonfunctional, piece of DNA called a pseudogene, which is located close to the SBDS gene on chromosome 7. This type of DNA exchange is called a gene conversion. The genetic material from the pseudogene contains errors that, when introduced into the SBDS gene, disrupt the way the gene's instructions are used to make a protein.
The two most common mutations in people with Shwachman-Diamond syndrome result from exchanges between the SBDS gene and the nearby pseudogene. One of these mutations, written as 258+2T>C, changes a single DNA building block (nucleotide) in a region of the gene known as intron 2. This mutation, which is called a splice-site mutation, prevents the production of functional SBDS protein. Other splice-site mutations in the SBDS gene can also cause Shwachman-Diamond syndrome. The other common mutation, written as 183_184delTAinsCT, changes two nucleotides in the SBDS gene. This genetic change introduces a premature stop signal in the instructions for making the SBDS protein. It is unclear whether this mutation results in an abnormally shortened protein or prevents any protein from being made.
The features of Shwachman-Diamond syndrome result when mutations reduce the amount or impair the function of the SBDS protein. Researchers are unsure how a reduction of functional SBDS protein causes the condition. They suspect a shortage of SBDS protein impairs ribosome formation, which may reduce the production of other proteins and alter developmental processes. It is unclear whether disruption of other cellular functions contribute to the features of Shwachman-Diamond syndrome.More About This Health Condition
Other Names for This Gene
- SBDS ribosome assembly guanine nucleotide exchange factor
- SBDS, ribosome assembly guanine nucleotide exchange factor
- Shwachman-Bodian-Diamond syndrome
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Austin KM, Gupta ML Jr, Coats SA, Tulpule A, Mostoslavsky G, Balazs AB, Mulligan RC, Daley G, Pellman D, Shimamura A. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J Clin Invest. 2008 Apr;118(4):1511-8. doi: 10.1172/JCI33764. Citation on PubMed or Free article on PubMed Central
- Ball HL, Zhang B, Riches JJ, Gandhi R, Li J, Rommens JM, Myers JS. Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses. Hum Mol Genet. 2009 Oct 1;18(19):3684-95. doi: 10.1093/hmg/ddp316. Epub 2009 Jul 14. Citation on PubMed or Free article on PubMed Central
- Boocock GR, Marit MR, Rommens JM. Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. Genomics. 2006 Jun;87(6):758-71. Epub 2006 Mar 10. Citation on PubMed
- Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet. 2003 Jan;33(1):97-101. Epub 2002 Dec 23. Citation on PubMed
- Calamita P, Miluzio A, Russo A, Pesce E, Ricciardi S, Khanim F, Cheroni C, Alfieri R, Mancino M, Gorrini C, Rossetti G, Peluso I, Pagani M, Medina DL, Rommens J, Biffo S. SBDS-Deficient Cells Have an Altered Homeostatic Equilibrium due to Translational Inefficiency Which Explains their Reduced Fitness and Provides a Logical Framework for Intervention. PLoS Genet. 2017 Jan 5;13(1):e1006552. doi: 10.1371/journal.pgen.1006552. eCollection 2017 Jan. Citation on PubMed or Free article on PubMed Central
- Dror Y. Shwachman-Diamond syndrome. Pediatr Blood Cancer. 2005 Dec;45(7):892-901. Review. Citation on PubMed
- Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, González Fernández A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanné-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. doi: 10.1101/gad.623011. Citation on PubMed or Free article on PubMed Central
- Ganapathi KA, Austin KM, Lee CS, Dias A, Malsch MM, Reed R, Shimamura A. The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood. 2007 Sep 1;110(5):1458-65. Epub 2007 May 2. Citation on PubMed or Free article on PubMed Central
- Orelio C, Kuijpers TW. Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics. Haematologica. 2009 Mar;94(3):409-13. doi: 10.3324/haematol.13733. Epub 2009 Feb 11. Citation on PubMed or Free article on PubMed Central
- Savchenko A, Krogan N, Cort JR, Evdokimova E, Lew JM, Yee AA, Sánchez-Pulido L, Andrade MA, Bochkarev A, Watson JD, Kennedy MA, Greenblatt J, Hughes T, Arrowsmith CH, Rommens JM, Edwards AM. The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism. J Biol Chem. 2005 May 13;280(19):19213-20. Epub 2005 Feb 8. Citation on PubMed
- Shammas C, Menne TF, Hilcenko C, Michell SR, Goyenechea B, Boocock GR, Durie PR, Rommens JM, Warren AJ. Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome. J Biol Chem. 2005 May 13;280(19):19221-9. Epub 2005 Feb 8. Citation on PubMed
- Shimamura A. Shwachman-Diamond syndrome. Semin Hematol. 2006 Jul;43(3):178-88. Review. Citation on PubMed
- Weis F, Giudice E, Churcher M, Jin L, Hilcenko C, Wong CC, Traynor D, Kay RR, Warren AJ. Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Nat Struct Mol Biol. 2015 Nov;22(11):914-9. doi: 10.1038/nsmb.3112. Epub 2015 Oct 19. Citation on PubMed or Free article on PubMed Central
- Woloszynek JR, Rothbaum RJ, Rawls AS, Minx PJ, Wilson RK, Mason PJ, Bessler M, Link DC. Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome. Blood. 2004 Dec 1;104(12):3588-90. Epub 2004 Jul 29. Citation on PubMed