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Genetics Home Reference: your guide to understanding genetic conditions
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MED12

Reviewed April 2013

What is the official name of the MED12 gene?

The official name of this gene is “mediator complex subunit 12.”

MED12 is the gene's official symbol. The MED12 gene is also known by other names, listed below.

What is the normal function of the MED12 gene?

The MED12 gene provides instructions for making a protein called mediator complex subunit 12. As its name suggests, this protein forms one part (subunit) of the mediator complex, which is a group of about 25 proteins that work together to regulate gene activity. The mediator complex physically links transcription factors, which are proteins that influence whether genes are turned on or off, with an enzyme called RNA polymerase II. Once transcription factors are attached, this enzyme initiates gene transcription, the process by which information stored in a gene's DNA is used to build proteins.

Researchers believe that the MED12 protein is involved in many aspects of early development, including the development of nerve cells (neurons) in the brain. The MED12 protein is part of several chemical signaling pathways within cells. These pathways help direct a broad range of cellular activities, such as cell growth, cell movement (migration), and the process by which cells mature to carry out specific functions (differentiation).

How are changes in the MED12 gene related to health conditions?

FG syndrome - caused by mutations in the MED12 gene

At least two mutations in the MED12 gene have been found to cause FG syndrome, which is characterized by intellectual disability, behavioral problems, and physical abnormalities including weak muscle tone (hypotonia) and obstruction of the anal opening (imperforate anus).

The mutations that cause FG syndrome each change a single protein building block (amino acid) in the MED12 protein. One mutation replaces the amino acid arginine with the amino acid tryptophan at protein position 961 (written as Arg961Trp or R961W). The other replaces the amino acid glycine with the amino acid glutamic acid at protein position 958 (written as Gly958Glu or G958E). These mutations alter the structure of the MED12 protein, which likely disrupts its ability to regulate gene activity during development. However, it is unclear how the genetic changes lead to intellectual disability and the other features of FG syndrome.

Lujan syndrome - caused by mutations in the MED12 gene

At least one mutation in the MED12 gene causes Lujan syndrome, a disorder characterized by intellectual disability, behavioral problems, and physical features including tall stature and a long, narrow face. This mutation is different than the genetic changes associated with FG syndrome (described above); the Lujan syndrome mutation replaces the amino acid asparagine with the amino acid serine at position 1007 of the MED12 protein (written as Asn1007Ser or N1007S). The mutation alters the structure of the MED12 protein and likely disrupts its ability to regulate gene activity, but it is not known how these changes affect development and lead to the specific features of Lujan syndrome.

Ohdo syndrome, Maat-Kievit-Brunner type - caused by mutations in the MED12 gene

At least three MED12 gene mutations have been found to cause the Maat-Kievit-Brunner type of Ohdo syndrome, which is a rare condition characterized by intellectual disability and distinctive facial features. The mutations that cause this disorder change single amino acids in the MED12 gene, although they are not the same genetic changes that cause FG syndrome or Lujan syndrome (described above). The mutations that result in the Maat-Kievit-Brunner type of Ohdo syndrome change the structure of the MED12 gene, impairing its ability to control gene activity. It is unclear how these changes lead to the particular cognitive and physical features of the disorder.

tumors - associated with the MED12 gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are known as somatic mutations, are not inherited. Somatic mutations in the MED12 gene have been found in several types of tumors, both noncancerous and cancerous.

Somatic MED12 gene mutations are present in most uterine leiomyomas, which are noncancerous growths also known as uterine fibroids. Uterine leiomyomas are common in adult women. These growths can cause pelvic pain and abnormal bleeding, and, in some cases, lead to an inability to have biological children (infertility). Somatic MED12 gene mutations have also been identified in some cancerous uterine tumors, including leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), and in some prostate and colorectal cancers.

Studies suggest that somatic MED12 gene mutations alter the function of the MED12 protein, which likely disrupts normal cell signaling and impairs regulation of cell growth and other cell functions. As a result, certain cells may become able to divide in an uncontrolled way, leading to the growth of a tumor.

other disorders - associated with the MED12 gene

A particular variation (polymorphism) in the MED12 gene, known as the HOPA(12bp) polymorphism, has been associated with a modestly increased risk of schizophrenia in people of northern European ancestry. This variation is an insertion of 12 extra DNA building blocks (base pairs) in the MED12 gene, which leads to an extra four amino acids in the MED12 protein. Because this protein is involved in several different signaling pathways, it has been difficult to determine the effects of the variation on brain function. The HOPA(12bp) polymorphism is among many factors under study to help explain the causes of schizophrenia. A large number of genetic and lifestyle factors, most of which remain unknown, likely determine the risk of developing this condition.

Where is the MED12 gene located?

Cytogenetic Location: Xq13

Molecular Location on the X chromosome: base pairs 71,118,555 to 71,142,453

The MED12 gene is located on the long (q) arm of the X chromosome at position 13.

The MED12 gene is located on the long (q) arm of the X chromosome at position 13.

More precisely, the MED12 gene is located from base pair 71,118,555 to base pair 71,142,453 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 MED12?

You and your healthcare professional may find the following resources about MED12 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 MED12 gene or gene products?

  • CAGH45
  • HOPA
  • KIAA0192
  • MED12_HUMAN
  • mediator of RNA polymerase II transcription, subunit 12 homolog
  • OKS
  • OPA1
  • OPA-containing protein
  • thyroid hormone receptor-associated protein, 230 kDa subunit
  • TNRC11
  • TRAP230

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 MED12?

acids ; amino acid ; anus ; arginine ; asparagine ; benign ; cell ; colorectal ; differentiation ; disability ; DNA ; enzyme ; gene ; gene transcription ; glutamic acid ; glycine ; hormone ; hypotonia ; imperforate anus ; infertility ; inherited ; insertion ; mediator complex ; muscle tone ; mutation ; obstruction ; polymorphism ; prostate ; protein ; receptor ; RNA ; RNA polymerase ; schizophrenia ; serine ; stature ; subunit ; syndrome ; thyroid ; transcription ; tryptophan ; tumor

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

References

  • Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet. 2012 May 20;44(6):685-9. doi: 10.1038/ng.2279. (http://www.ncbi.nlm.nih.gov/pubmed/22610119?dopt=Abstract)
  • Ding N, Zhou H, Esteve PO, Chin HG, Kim S, Xu X, Joseph SM, Friez MJ, Schwartz CE, Pradhan S, Boyer TG. Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation. Mol Cell. 2008 Aug 8;31(3):347-59. doi: 10.1016/j.molcel.2008.05.023. (http://www.ncbi.nlm.nih.gov/pubmed/18691967?dopt=Abstract)
  • Gene Review: MED12-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1676)
  • Je EM, Kim MR, Min KO, Yoo NJ, Lee SH. Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer. 2012 Sep 15;131(6):E1044-7. doi: 10.1002/ijc.27610. Epub 2012 May 8. (http://www.ncbi.nlm.nih.gov/pubmed/22532225?dopt=Abstract)
  • Kämpjärvi K, Mäkinen N, Kilpivaara O, Arola J, Heinonen HR, Böhm J, Abdel-Wahab O, Lehtonen HJ, Pelttari LM, Mehine M, Schrewe H, Nevanlinna H, Levine RL, Hokland P, Böhling T, Mecklin JP, Bützow R, Aaltonen LA, Vahteristo P. Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. Br J Cancer. 2012 Nov 6;107(10):1761-5. doi: 10.1038/bjc.2012.428. Epub 2012 Sep 20. (http://www.ncbi.nlm.nih.gov/pubmed/23132392?dopt=Abstract)
  • Mäkinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, Gentile M, Yan J, Enge M, Taipale M, Aavikko M, Katainen R, Virolainen E, Böhling T, Koski TA, Launonen V, Sjöberg J, Taipale J, Vahteristo P, Aaltonen LA. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 2011 Oct 14;334(6053):252-5. doi: 10.1126/science.1208930. Epub 2011 Aug 25. (http://www.ncbi.nlm.nih.gov/pubmed/21868628?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9968)
  • Pérot G, Croce S, Ribeiro A, Lagarde P, Velasco V, Neuville A, Coindre JM, Stoeckle E, Floquet A, MacGrogan G, Chibon F. MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS One. 2012;7(6):e40015. doi: 10.1371/journal.pone.0040015. Epub 2012 Jun 29. (http://www.ncbi.nlm.nih.gov/pubmed/22768200?dopt=Abstract)
  • Philibert RA, Bohle P, Secrest D, Deaderick J, Sandhu H, Crowe R, Black DW. The association of the HOPA(12bp) polymorphism with schizophrenia in the NIMH Genetics Initiative for Schizophrenia sample. Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):743-7. (http://www.ncbi.nlm.nih.gov/pubmed/17299734?dopt=Abstract)
  • Philibert RA, Madan A. Role of MED12 in transcription and human behavior. Pharmacogenomics. 2007 Aug;8(8):909-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17716226?dopt=Abstract)
  • Philibert RA. A meta-analysis of the association of the HOPA12bp polymorphism and schizophrenia. Psychiatr Genet. 2006 Apr;16(2):73-6. (http://www.ncbi.nlm.nih.gov/pubmed/16538184?dopt=Abstract)
  • Risheg H, Graham JM Jr, Clark RD, Rogers RC, Opitz JM, Moeschler JB, Peiffer AP, May M, Joseph SM, Jones JR, Stevenson RE, Schwartz CE, Friez MJ. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet. 2007 Apr;39(4):451-3. Epub 2007 Mar 4. (http://www.ncbi.nlm.nih.gov/pubmed/17334363?dopt=Abstract)
  • Rump P, Niessen RC, Verbruggen KT, Brouwer OF, de Raad M, Hordijk R. A novel mutation in MED12 causes FG syndrome (Opitz-Kaveggia syndrome). Clin Genet. 2011 Feb;79(2):183-8. doi: 10.1111/j.1399-0004.2010.01449.x. (http://www.ncbi.nlm.nih.gov/pubmed/20507344?dopt=Abstract)
  • Schwartz CE, Tarpey PS, Lubs HA, Verloes A, May MM, Risheg H, Friez MJ, Futreal PA, Edkins S, Teague J, Briault S, Skinner C, Bauer-Carlin A, Simensen RJ, Joseph SM, Jones JR, Gecz J, Stratton MR, Raymond FL, Stevenson RE. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet. 2007 Jul;44(7):472-7. Epub 2007 Mar 16. (http://www.ncbi.nlm.nih.gov/pubmed/17369503?dopt=Abstract)
  • Vulto-van Silfhout AT, de Vries BB, van Bon BW, Hoischen A, Ruiterkamp-Versteeg M, Gilissen C, Gao F, van Zwam M, Harteveld CL, van Essen AJ, Hamel BC, Kleefstra T, Willemsen MA, Yntema HG, van Bokhoven H, Brunner HG, Boyer TG, de Brouwer AP. Mutations in MED12 cause X-linked Ohdo syndrome. Am J Hum Genet. 2013 Mar 7;92(3):401-6. doi: 10.1016/j.ajhg.2013.01.007. Epub 2013 Feb 7. (http://www.ncbi.nlm.nih.gov/pubmed/23395478?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: April 2013
Published: November 24, 2014