Reviewed November 2007
What is the official name of the MID1 gene?
The official name of this gene is “midline 1 (Opitz/BBB syndrome).”
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 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 breaks down (degrades) unwanted proteins by tagging them with molecules called ubiquitin. Ubiquitin serves as a signal to move these unwanted proteins into specialized structures known as proteasomes, where the proteins are degraded.
The MID1 gene provides instructions for making a protein called midin or midline-1. This protein helps regulate the function of 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 transport of materials within cells. As part of its protein degrading function, midin is responsible for breaking down an enzyme called protein phosphatase 2A (PP2A). This enzyme activates a number of microtubule-associated proteins.
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 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
More than 40 mutations in the MID1 gene have been identified in people with X-linked Opitz G/BBB syndrome. The majority of these mutations change a single protein building block (amino acid) in the midin protein. Other mutations include deletions or insertions of more than one amino acid and splice site mutations, which cause the protein to be pieced together incorrectly. All these mutations cause the non-functioning midin to be unable to attach (bind) to microtubules and break down PP2A. As a result, PP2A builds up in cells. An excess of this protein abnormally alters the functions of microtubule-associated proteins, which in turn can disrupt the normal function of microtubules. It is unclear how these changes interfere with normal development and cause the birth defects associated with Opitz G/BBB syndrome. Researchers speculate that the nonfunctional midin affects how the cells divide and associate along the midline of the body during development, resulting in many of the abnormalities seen in Opitz G/BBB syndrome.
Where is the MID1 gene located?
Cytogenetic Location: Xp22
Molecular Location on the X chromosome: base pairs 10,413,349 to 10,851,808
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 10,413,349 to base pair 10,851,808 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.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1327/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for MID1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4281%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((MID1%5BTI%5D)%20OR%20(midline%201%5BTIAB%5D))%20AND%20(Genes%5BMH%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/300552)
Research Resources - Tools for researchers
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4281)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4281)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=7095)
What other names do people use for the MID1 gene or gene products?
- midline 1 ring finger
- 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?
amino acid ;
cell division ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Cainarca S, Messali S, Ballabio A, Meroni G. Functional characterization of the Opitz syndrome gene product (midin): evidence for homodimerization and association with microtubules throughout the cell cycle. Hum Mol Genet. 1999 Aug;8(8):1387-96. (http://www.ncbi.nlm.nih.gov/pubmed/10400985?dopt=Abstract)
- 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)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4281)
- 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)
- 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)
- 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)
- OMIM: MIDLINE 1 (http://omim.org/entry/300552)
- Pinson L, Augé J, Audollent S, Mattéi G, Etchevers H, Gigarel N, Razavi F, Lacombe D, Odent S, Le Merrer M, Amiel J, Munnich A, Meroni G, Lyonnet S, Vekemans M, Attié-Bitach T. Embryonic expression of the human MID1 gene and its mutations in Opitz syndrome. J Med Genet. 2004 May;41(5):381-6. (http://www.ncbi.nlm.nih.gov/pubmed/15121778?dopt=Abstract)
- 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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.