The CUL7 gene provides instructions for making a protein called cullin-7. This 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, cullin-7 is thought to help regulate proteins involved in the body's response to growth hormones, although its specific role in this process is unknown.
Health Conditions Related to Genetic Changes
At least 73 mutations in the CUL7 gene have been identified in people with 3-M syndrome, a disorder that causes skeletal anomalies 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 cullin-7 protein or result in a cullin-7 protein that is abnormally short and nonfunctional.
Individuals in the Yakut population of the Russian province of Siberia with a variant of 3-M syndrome all have a particular mutation in both copies of the CUL7 gene in each cell. This mutation replaces the amino acid glutamine with a premature stop signal in the instructions for making the cullin-7 protein (written as Gln1553Ter or Q1553X), leading to production of an abnormally short protein.
Mutations in the CUL7 gene, including the Gln1553Ter mutation, prevent the cullin-7 protein from bringing together the components of the E3 ubiquitin ligase complex, 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 CUL7 gene mutations and the signs and symptoms of 3-M syndrome are unknown.More About This Health Condition
Other Names for This Gene
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- 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
- Huber C, Dias-Santagata D, Glaser A, O'Sullivan J, Brauner R, Wu K, Xu X, Pearce K, Wang R, Uzielli ML, Dagoneau N, Chemaitilly W, Superti-Furga A, Dos Santos H, Mégarbané A, Morin G, Gillessen-Kaesbach G, Hennekam R, Van der Burgt I, Black GC, Clayton PE, Read A, Le Merrer M, Scambler PJ, Munnich A, Pan ZQ, Winter R, Cormier-Daire V. Identification of mutations in CUL7 in 3-M syndrome. Nat Genet. 2005 Oct;37(10):1119-24. Epub 2005 Sep 4. 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
- Maksimova N, Hara K, Miyashia A, Nikolaeva I, Shiga A, Nogovicina A, Sukhomyasova A, Argunov V, Shvedova A, Ikeuchi T, Nishizawa M, Kuwano R, Onodera O. Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia. J Med Genet. 2007 Dec;44(12):772-8. Epub 2007 Aug 3. Citation on PubMed or Free article on PubMed Central