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MID1 gene

midline 1

Normal Function

The MID1 gene is part of a group of genes called the tripartite motif (TRIM) family. Proteins produced from this large family of genes are involved in many cellular activities. Primarily, TRIM proteins play a role in the cell machinery that recycles unwanted proteins by tagging them with a protein called ubiquitin. Ubiquitin serves as a signal to move these unwanted proteins into specialized structures known as proteasomes, where the proteins are recycled.

The MID1 gene provides instructions for making a protein called midline-1. This protein attaches (binds) to microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the movement of cells (cell migration). Midline-1 is responsible for recycling certain proteins, including protein phosphatase 2A (PP2A), integrin alpha-4 (ITGA4), and serine/threonine-protein kinase 36 (STK36). The recycling of these three proteins so they can be reused instead of broken down is essential because they are necessary for normal cellular functioning.

Health Conditions Related to Genetic Changes

Opitz G/BBB syndrome

About 90 mutations in the MID1 gene have been found to cause Opitz G/BBB syndrome. This condition causes several abnormalities along the midline of the body, including widely spaced eyes (ocular hypertelorism), difficulty breathing or swallowing, brain malformations, distinct facial features, and genital abnormalities in males. The majority of the MID1 gene mutations change a single protein building block (amino acid) in the midline-1 protein. Other mutations delete multiple amino acids and can result in the production of an abnormally short protein. These mutations lead to a decrease in midline-1 function, which prevents protein recycling. As a result, certain proteins are not recycled, and they accumulate in cells. This buildup impairs microtubule function, resulting in problems with cell division and migration. Researchers speculate that the altered midline-1 protein affects how the cells divide and migrate along the midline of the body during development, resulting in the features of Opitz G/BBB syndrome.

More About This Health Condition

Other Names for This Gene

  • BBBG1
  • FXY
  • GBBB1
  • midline 1 (Opitz/BBB syndrome)
  • midline 1 ring finger
  • midline-1
  • OGS1
  • OS
  • OSX
  • RNF59
  • TRIM18
  • XPRF
  • zinc finger X and Y

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


  • De Falco F, Cainarca S, Andolfi G, Ferrentino R, Berti C, Rodriguez Criado G, Rittinger O, Dennis N, Odent S, Rastogi A, Liebelt J, Chitayat D, Winter R, Jawanda H, Ballabio A, Franco B, Meroni G. X-linked Opitz syndrome: novel mutations in the MID1 gene and redefinition of the clinical spectrum. Am J Med Genet A. 2003 Jul 15;120A(2):222-8. doi: 10.1002/ajmg.a.10265. Citation on PubMed
  • Du H, Huang Y, Zaghlula M, Walters E, Cox TC, Massiah MA. The MID1 E3 ligase catalyzes the polyubiquitination of Alpha4 (alpha4), a regulatory subunit of protein phosphatase 2A (PP2A): novel insights into MID1-mediated regulation of PP2A. J Biol Chem. 2013 Jul 19;288(29):21341-21350. doi: 10.1074/jbc.M113.481093. Epub 2013 Jun 5. Citation on PubMed or Free article on PubMed Central
  • Du H, Wu K, Didoronkute A, Levy MV, Todi N, Shchelokova A, Massiah MA. MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac. PLoS One. 2014 Sep 10;9(9):e107428. doi: 10.1371/journal.pone.0107428. eCollection 2014. Citation on PubMed or Free article on PubMed Central
  • Ferrentino R, Bassi MT, Chitayat D, Tabolacci E, Meroni G. MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients: twenty-nine novel mutations identified. Hum Mutat. 2007 Feb;28(2):206-7. doi: 10.1002/humu.9480. Citation on PubMed
  • Fontanella B, Russolillo G, Meroni G. MID1 mutations in patients with X-linked Opitz G/BBB syndrome. Hum Mutat. 2008 May;29(5):584-94. doi: 10.1002/humu.20706. Citation on PubMed
  • Han X, Du H, Massiah MA. Detection and characterization of the in vitro e3 ligase activity of the human MID1 protein. J Mol Biol. 2011 Apr 8;407(4):505-20. doi: 10.1016/j.jmb.2011.01.048. Epub 2011 Feb 4. Citation on PubMed
  • Liu J, Prickett TD, Elliott E, Meroni G, Brautigan DL. Phosphorylation and microtubule association of the Opitz syndrome protein mid-1 is regulated by protein phosphatase 2A via binding to the regulatory subunit alpha 4. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6650-5. doi: 10.1073/pnas.111154698. Epub 2001 May 22. Citation on PubMed or Free article on PubMed Central
  • Mnayer L, Khuri S, Merheby HA, Meroni G, Elsas LJ. A structure-function study of MID1 mutations associated with a mild Opitz phenotype. Mol Genet Metab. 2006 Mar;87(3):198-203. doi: 10.1016/j.ymgme.2005.10.014. Citation on PubMed
  • Quaderi NA, Schweiger S, Gaudenz K, Franco B, Rugarli EI, Berger W, Feldman GJ, Volta M, Andolfi G, Gilgenkrantz S, Marion RW, Hennekam RC, Opitz JM, Muenke M, Ropers HH, Ballabio A. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet. 1997 Nov;17(3):285-91. doi: 10.1038/ng1197-285. Citation on PubMed
  • Schweiger S, Schneider R. The MID1/PP2A complex: a key to the pathogenesis of Opitz BBB/G syndrome. Bioessays. 2003 Apr;25(4):356-66. doi: 10.1002/bies.10256. Citation on PubMed
  • Trockenbacher A, Suckow V, Foerster J, Winter J, Krauss S, Ropers HH, Schneider R, Schweiger S. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat Genet. 2001 Nov;29(3):287-94. doi: 10.1038/ng762. Erratum In: Nat Genet 2002 Jan;30(1):123. 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.