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OBSL1 gene

obscurin like 1
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Normal Function

The OBSL1 gene provides instructions for making a protein that is thought to help maintain normal levels of another protein called cullin-7, which is produced from the CUL7 gene. The cullin-7 protein plays a role in the ubiquitin-proteasome system, which is the cell machinery that breaks down (degrades) unwanted proteins.

Cullin-7 helps assemble a complex known as an E3 ubiquitin ligase. This complex tags damaged and excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. In particular, the OBSL1 protein and cullin-7 are thought to help regulate proteins involved in the body's response to growth hormones, although their specific role in this process is unknown.

Health Conditions Related to Genetic Changes

3-M syndrome

At least 29 mutations in the OBSL1 gene have been identified in people with 3-M syndrome, a disorder that causes skeletal abnormalities including short stature (dwarfism) and unusual facial features. Most of these mutations substitute one protein building block (amino acid) for another amino acid in the OBSL1 protein or result in an OBSL1 protein that is abnormally short and nonfunctional.

Mutations in the OBSL1 gene likely lead to reduced cullin-7 protein levels, preventing cullin-7 from bringing together the components of the E3 ubiquitin ligase complex and interfering with the process of tagging unneeded proteins for degradation. The body's response to growth hormones may be impaired as a result. However, the specific relationship between OBSL1 gene mutations and the signs and symptoms of 3-M syndrome are unknown.

More About This Health Condition

Other Names for This Gene

  • KIAA0657
  • obscurin-like protein 1 isoform 1 precursor
  • obscurin-like protein 1 isoform 2 precursor
  • obscurin-like protein 1 isoform 3 precursor

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Clayton PE, Hanson D, Magee L, Murray PG, Saunders E, Abu-Amero SN, Moore GE, Black GC. Exploring the spectrum of 3-M syndrome, a primordial short stature disorder of disrupted ubiquitination. Clin Endocrinol (Oxf). 2012 Sep;77(3):335-42. doi: 10.1111/j.1365-2265.2012.04428.x. Review. Citation on PubMed
  • Hanson D, Murray PG, Black GC, Clayton PE. The genetics of 3-M syndrome: unravelling a potential new regulatory growth pathway. Horm Res Paediatr. 2011;76(6):369-78. doi: 10.1159/000334392. Epub 2011 Nov 29. Review. Citation on PubMed
  • Hanson D, Murray PG, Coulson T, Sud A, Omokanye A, Stratta E, Sakhinia F, Bonshek C, Wilson LC, Wakeling E, Temtamy SA, Aglan M, Rosser EM, Mansour S, Carcavilla A, Nampoothiri S, Khan WI, Banerjee I, Chandler KE, Black GC, Clayton PE. Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling. J Mol Endocrinol. 2012 Oct 30;49(3):267-75. doi: 10.1530/JME-12-0034. Print 2012 Dec. Citation on PubMed
  • Hanson D, Murray PG, Sud A, Temtamy SA, Aglan M, Superti-Furga A, Holder SE, Urquhart J, Hilton E, Manson FD, Scambler P, Black GC, Clayton PE. The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1. Am J Hum Genet. 2009 Jun;84(6):801-6. doi: 10.1016/j.ajhg.2009.04.021. Epub 2009 May 28. Citation on PubMed or Free article on PubMed Central
  • Huber C, Fradin M, Edouard T, Le Merrer M, Alanay Y, Da Silva DB, David A, Hamamy H, van Hest L, Lund AM, Michaud J, Oley C, Patel C, Rajab A, Skidmore DL, Stewart H, Tauber M, Munnich A, Cormier-Daire V. OBSL1 mutations in 3-M syndrome are associated with a modulation of IGFBP2 and IGFBP5 expression levels. Hum Mutat. 2010 Jan;31(1):20-6. doi: 10.1002/humu.21150. Citation on PubMed
  • Irving M, Holder-Espinasse M. Three M Syndrome. 2002 Mar 25 [updated 2019 Feb 7]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews┬« [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1481/ Citation on PubMed
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