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Genetics Home Reference: your guide to understanding genetic conditions
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MID1

Reviewed January 2015

What is the official name of the MID1 gene?

The official name of this gene is “midline 1.”

MID1 is the gene's official symbol. The MID1 gene is also known by other names, listed below.

What is the normal function of the MID1 gene?

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.

Does the MID1 gene share characteristics with other genes?

The MID1 gene belongs to a family of genes called fibronectin type III domain containing (fibronectin type III domain containing). It also belongs to a family of genes called RNF (RING-type zinc fingers). It also belongs to a family of genes called TRIM (tripartite motif-containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the MID1 gene related to health conditions?

Opitz G/BBB syndrome - caused by mutations in the MID1 gene

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.

Where is the MID1 gene located?

Cytogenetic Location: Xp22

Molecular Location on the X chromosome: base pairs 10,445,309 to 10,833,709

The MID1 gene is located on the short (p) arm of the X chromosome at position 22.

The MID1 gene is located on the short (p) arm of the X chromosome at position 22.

More precisely, the MID1 gene is located from base pair 10,445,309 to base pair 10,833,709 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about MID1?

You and your healthcare professional may find the following resources about MID1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the MID1 gene or gene products?

  • BBBG1
  • FXY
  • GBBB1
  • midline-1
  • midline 1 (Opitz/BBB syndrome)
  • midline 1 ring finger
  • OGS1
  • OS
  • OSX
  • RNF59
  • TRI18_HUMAN
  • TRIM18
  • XPRF
  • zinc finger X and Y

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding MID1?

acids ; amino acid ; BBB ; cell ; cell division ; cytoskeleton ; gene ; hypertelorism ; kinase ; microtubule ; motif ; ocular hypertelorism ; phosphatase ; protein ; serine ; syndrome ; threonine ; ubiquitin

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • De Falco F, Cainarca S, Andolfi G, Ferrentino R, Berti C, Rodríguez 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12833403?dopt=Abstract)
  • Du H, Huang Y, Zaghlula M, Walters E, Cox TC, Massiah MA. The MID1 E3 ligase catalyzes the polyubiquitination of Alpha4 (α4), a regulatory subunit of protein phosphatase 2A (PP2A): novel insights into MID1-mediated regulation of PP2A. J Biol Chem. 2013 Jul 19;288(29):21341-50. doi: 10.1074/jbc.M113.481093. Epub 2013 Jun 5. (http://www.ncbi.nlm.nih.gov/pubmed/23740247?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/25207814?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/17221865?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18360914?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/21296087?dopt=Abstract)
  • 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. Epub 2001 May 22. (http://www.ncbi.nlm.nih.gov/pubmed/11371618?dopt=Abstract)
  • OMIM: MIDLINE 1 (http://omim.org/entry/300552)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16378742?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4281)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/9354791?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12655643?dopt=Abstract)
  • 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. Erratum in: Nat Genet 2002 Jan;30(1):123. (http://www.ncbi.nlm.nih.gov/pubmed/11685209?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2015
Published: March 2, 2015