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Genetics Home Reference: your guide to understanding genetic conditions
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MECP2

Reviewed October 2011

What is the official name of the MECP2 gene?

The official name of this gene is “methyl CpG binding protein 2 (Rett syndrome).”

MECP2 is the gene's official symbol. The MECP2 gene is also known by other names, listed below.

What is the normal function of the MECP2 gene?

The MECP2 gene provides instructions for making a protein, known as MeCP2, whose exact function is unclear. It appears to help regulate gene activity (expression) by modifying chromatin, the complex of DNA and protein that packages DNA into chromosomes. The MeCP2 protein usually regulates genes involved in brain function, even though this protein is found throughout the body.

Within the brain, the MeCP2 protein is important for the function of nerve cells (neurons) and is present in high levels in mature neurons. This protein likely plays a role in maintaining connections (synapses) between neurons, where cell-to-cell communication occurs. Many of the genes that are known to be regulated by the MeCP2 protein play a role in normal brain function, particularly the maintenance of synapses.

Researchers believe that the MeCP2 protein is also involved in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the MeCP2 protein controls the production of different versions of certain proteins. This process is known as alternative splicing. In the brain, the alternative splicing of proteins is critical for normal communication between neurons.

How are changes in the MECP2 gene related to health conditions?

MECP2 duplication syndrome - caused by mutations in the MECP2 gene

An extra copy of the MECP2 gene in each cell causes MECP2 duplication syndrome, a condition characterized by intellectual disability, delayed development, and seizures. This additional copy of the MECP2 gene is caused by a duplication of genetic material on the long (q) arm of the X chromosome. The size of the duplication varies from 100,000 to 900,000 DNA building blocks (base pairs), also written as 100 to 900 kilobases (kb).

Duplication of the MECP2 gene leads to the production of extra MeCP2 protein. This overproduction results in an inability of the protein to regulate the expression of other genes properly. The misregulation of gene expression in the brain results in abnormal neuronal function. These neuronal abnormalities cause irregular brain activity, leading to the signs and symptoms of MECP2 duplication.

MECP2-related severe neonatal encephalopathy - caused by mutations in the MECP2 gene

Mutations in the MECP2 gene cause MECP2-related severe neonatal encephalopathy. These mutations cause small head size (microcephaly), movement disorders, breathing problems, and seizures in affected males. Many of the MECP2 gene mutations that cause this condition in males cause a similar disorder called Rett syndrome in females. Most of these mutations change single base pairs, insert or delete base pairs in the gene, or change how the gene is processed into a protein. These changes in DNA alter the structure of the MeCP2 protein or reduce the amount of protein that is produced. As a result, cells do not have enough MeCP2 protein to bind to DNA and silence other genes. Genes that are normally regulated by this protein remain active and continue to make proteins when they are not needed. Mutations in the MECP2 gene may also disrupt alternative splicing of proteins critical for communication between neurons. Although these defects disrupt normal brain development, it remains unclear how MECP2 gene mutations lead to the signs and symptoms of MECP2-related severe neonatal encephalopathy.

PPM-X syndrome - caused by mutations in the MECP2 gene

Mutations in the MECP2 gene have been found to cause PPM-X syndrome. Eight particular mutations are responsible for approximately half of all cases of PPM-X syndrome. These mutations either change single protein building blocks (amino acids) in the MeCP2 protein or create a premature stop signal in the instructions for making the protein. Mutations that cause PPM-X syndrome lead to the production of a MeCP2 protein that cannot properly interact with DNA or other proteins and so cannot control the expression of genes. It is unclear how MECP2 gene mutations lead to the signs and symptoms of PPM-X syndrome, but misregulation of genes in the brain likely play a role in the development of intellectual disability and movement and mood disorders in affected individuals.

Rett syndrome - caused by mutations in the MECP2 gene

More than 300 mutations in the MECP2 gene have been identified in females with Rett syndrome, a brain disorder that causes problems with communication, learning, and coordination. These mutations include changes in single base pairs, insertions or deletions of DNA in the gene, and changes that affect how the gene is processed into a protein. MECP2 gene mutations alter the structure of the MeCP2 protein or reduce the amount of protein that is produced. As a result, cells do not have enough MeCP2 protein to bind to DNA and regulate gene expression. Mutations in the MECP2 gene may also disrupt alternative splicing of proteins critical for communication between neurons. Although these defects disrupt normal brain development, it remains unclear how MECP2 gene mutations lead to the signs and symptoms of Rett syndrome.

other disorders - associated with the MECP2 gene

Mutations in the MECP2 gene have also been identified in people with several other disorders that affect the brain. For example, MECP2 gene mutations are associated with some cases of moderate to severe X-linked intellectual disability. In addition, several people with the features of Rett syndrome and signs and symptoms similar to Angelman syndrome (a condition characterized by intellectual disability, problems with movement, and inappropriate laughter and excitability) have mutations in the MECP2 gene. MECP2 gene mutations or changes in the gene's activity have been reported in some cases of autism, which is a developmental disorder that affects communication and social interaction.

Where is the MECP2 gene located?

Cytogenetic Location: Xq28

Molecular Location on the X chromosome: base pairs 153,287,263 to 153,363,187

The MECP2 gene is located on the long (q) arm of the X chromosome at position 28.

The MECP2 gene is located on the long (q) arm of the X chromosome at position 28.

More precisely, the MECP2 gene is located from base pair 153,287,263 to base pair 153,363,187 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 MECP2?

You and your healthcare professional may find the following resources about MECP2 helpful.

  • Educational resources - Information pages

    • Cincinnati Children's Hospital: MECP2-Related Disorders (http://www.cincinnatichildrens.org/WorkArea/DownloadAsset.aspx?id=85684)
    • Press Release: Discovery Provides New Clues About Causes of Rett Syndrome (Howard Hughes Medical Institute, October 17, 2005) (http://www.hhmi.org/news/zoghbi7.html)
    • Rett Syndrome Research Trust (http://www.rsrt.org/)

  • Gene Reviews - Clinical summary

    • Gene Review: Autism Spectrum Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1442/)
    • Gene Review: MECP2 Duplication Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1284/)
    • Gene Review: MECP2-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1497/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for MECP2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4204%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=((MECP2%5BTIAB%5D)%20OR%20(methyl%20CpG%20binding%20protein%202%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • ANGELMAN SYNDROME (http://omim.org/entry/105830)
    • AUTISM (http://omim.org/entry/209850)
    • METHYL-CpG-BINDING PROTEIN 2 (http://omim.org/entry/300005)
    • MENTAL RETARDATION, X-LINKED, SYNDROMIC 13 (http://omim.org/entry/300055)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_MECP2.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4204)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4204)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=6990)
    • International Rett Syndrome Foundation: RettBASE: IRSF MECP2 Variation Database (http://mecp2.chw.edu.au/cgi-bin/mecp2/views/basic.cgi?form=basic)
    • University of Edinburgh: MeCP2.org.uk (http://www.mecp2.org.uk/index.html)

What other names do people use for the MECP2 gene or gene products?

  • MECP2_HUMAN
  • MeCP2 protein
  • methyl CpG binding protein 2
  • MRX16
  • MRX79
  • PPMX
  • RTS
  • RTT

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 MECP2?

acids ; alternative splicing ; autism ; cell ; chromatin ; chromosome ; DNA ; duplication ; encephalopathy ; gene ; gene expression ; kb ; messenger RNA ; methyl ; microcephaly ; mRNA ; neonatal ; protein ; RNA ; splicing ; syndrome

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

References

  • Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. (http://www.ncbi.nlm.nih.gov/pubmed/10508514?dopt=Abstract)
  • Caballero IM, Hendrich B. MeCP2 in neurons: closing in on the causes of Rett syndrome. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R19-26. Review. Erratum in: Hum Mol Genet. 2005 Jul 15;14(14):2089. (http://www.ncbi.nlm.nih.gov/pubmed/15809268?dopt=Abstract)
  • Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML, Vance JM, Pericak-Vance MA. Identification of MeCP2 mutations in a series of females with autistic disorder. Pediatr Neurol. 2003 Mar;28(3):205-11. (http://www.ncbi.nlm.nih.gov/pubmed/12770674?dopt=Abstract)
  • Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007 Nov 8;56(3):422-37. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17988628?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/4204)
  • Francke U. Mechanisms of disease: neurogenetics of MeCP2 deficiency. Nat Clin Pract Neurol. 2006 Apr;2(4):212-21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16932552?dopt=Abstract)
  • Gonzales ML, LaSalle JM. The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep. 2010 Apr;12(2):127-34. doi: 10.1007/s11920-010-0097-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20425298?dopt=Abstract)
  • Ham AL, Kumar A, Deeter R, Schanen NC. Does genotype predict phenotype in Rett syndrome? J Child Neurol. 2005 Sep;20(9):768-78. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16225834?dopt=Abstract)
  • Kaufmann WE, Johnston MV, Blue ME. MeCP2 expression and function during brain development: implications for Rett syndrome's pathogenesis and clinical evolution. Brain Dev. 2005 Nov;27 Suppl 1:S77-S87. Epub 2005 Sep 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16182491?dopt=Abstract)
  • Kerr AM, Ravine D. Review article: breaking new ground with Rett syndrome. J Intellect Disabil Res. 2003 Nov;47(Pt 8):580-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14641805?dopt=Abstract)
  • Kishi N, Macklis JD. Dissecting MECP2 function in the central nervous system. J Child Neurol. 2005 Sep;20(9):753-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16225831?dopt=Abstract)
  • Lugtenberg D, Kleefstra T, Oudakker AR, Nillesen WM, Yntema HG, Tzschach A, Raynaud M, Rating D, Journel H, Chelly J, Goizet C, Lacombe D, Pedespan JM, Echenne B, Tariverdian G, O'Rourke D, King MD, Green A, van Kogelenberg M, Van Esch H, Gecz J, Hamel BC, van Bokhoven H, de Brouwer AP. Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum Genet. 2009 Apr;17(4):444-53. doi: 10.1038/ejhg.2008.208. Epub 2008 Nov 5. Erratum in: Eur J Hum Genet. 2009 May;17(5):697. (http://www.ncbi.nlm.nih.gov/pubmed/18985075?dopt=Abstract)
  • McGraw CM, Samaco RC, Zoghbi HY. Adult neural function requires MeCP2. Science. 2011 Jul 8;333(6039):186. doi: 10.1126/science.1206593. Epub 2011 Jun 2. (http://www.ncbi.nlm.nih.gov/pubmed/21636743?dopt=Abstract)
  • Neul JL, Zoghbi HY. Rett syndrome: a prototypical neurodevelopmental disorder. Neuroscientist. 2004 Apr;10(2):118-28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15070486?dopt=Abstract)
  • Samaco RC, Nagarajan RP, Braunschweig D, LaSalle JM. Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Hum Mol Genet. 2004 Mar 15;13(6):629-39. Epub 2004 Jan 20. (http://www.ncbi.nlm.nih.gov/pubmed/14734626?dopt=Abstract)
  • Schanen C, Houwink EJ, Dorrani N, Lane J, Everett R, Feng A, Cantor RM, Percy A. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet A. 2004 Apr 15;126A(2):129-40. (http://www.ncbi.nlm.nih.gov/pubmed/15057977?dopt=Abstract)
  • Shahbazian MD, Zoghbi HY. Rett syndrome and MeCP2: linking epigenetics and neuronal function. Am J Hum Genet. 2002 Dec;71(6):1259-72. Epub 2002 Nov 19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12442230?dopt=Abstract)
  • Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ, Andrews R, Bird AP. Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell. 2010 Feb 26;37(4):457-68. doi: 10.1016/j.molcel.2010.01.030. (http://www.ncbi.nlm.nih.gov/pubmed/20188665?dopt=Abstract)
  • Van den Veyver IB, Zoghbi HY. Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S147-51. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11738862?dopt=Abstract)
  • Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, Lugtenberg D, Bienvenu T, Jensen LR, Gecz J, Moraine C, Marynen P, Fryns JP, Froyen G. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet. 2005 Sep;77(3):442-53. Epub 2005 Jul 29. (http://www.ncbi.nlm.nih.gov/pubmed/16080119?dopt=Abstract)
  • Villard L. MECP2 mutations in males. J Med Genet. 2007 Jul;44(7):417-23. Epub 2007 Mar 9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17351020?dopt=Abstract)
  • Webb T, Latif F. Rett syndrome and the MECP2 gene. J Med Genet. 2001 Apr;38(4):217-23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11283201?dopt=Abstract)
  • Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF, Kang D, Richman R, Johnson JM, Berget S, Zoghbi HY. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17551-8. Epub 2005 Oct 26. Erratum in: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1656. (http://www.ncbi.nlm.nih.gov/pubmed/16251272?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: October 2011
Published: May 20, 2013