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MECP2 (methyl CpG binding protein 2 (Rett syndrome)) is a gene that provides instructions for making its protein product, MECP2, also referred to in the biochemical literature as MeCP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels. The MeCP2 protein is likely to be involved in turning off ("repressing" or "silencing") several other genes. This prevents the genes from making proteins when they are not needed. The MeCP2 protein binds to forms of DNA that have been methylated. The MeCP2 protein then interacts with other proteins to form a complex that turns off the gene. Methylation is a chemical alteration made to a "cytosine" (C) when it occurs in a particular DNA sequence, "CpG". Many genes have CpG islands, which frequently occur near the beginning of the gene. MECP2 does not bind to these islands in most cases, as they are not methylated. The expression of a few genes may be regulated through methylation of their CpG island, and MECP2 may play a role in a subset of these. Researchers have not yet determined which genes are targeted by the MeCP2 protein, but such genes are probably important for the normal function of the central nervous system.

The MECP2 gene is located on the long (q) arm of the X chromosome in band 28 ("Xq28"), from base pair 152,808,110 to base pair 152,878,611.

Rett syndrome is caused by mutations in the MECP2 gene. Several types of mutations have been identified in people with Rett syndrome. These mutations include changes in single base pairs (the building material of DNA), insertions or deletions of DNA in the gene, and changes that affect how the gene is processed into a protein. Mutations in the gene alter the structure of the MeCP2 protein or lead to reduced amounts of the protein. As a result, the protein is unable to bind to DNA or turn off other genes. Genes that are normally regulated by MeCP2 remain active and continue to make large amounts of particular proteins when they are not needed. This defect probably disrupts the normal functioning of nerve cells, leading to the signs and symptoms of Rett syndrome.

Mutations in the MECP2 gene have also been identified in people with several other disorders affecting the central nervous system. For example, MECP2 mutations are associated with some cases of moderate to severe X-linked mental retardation. Mutations in the gene have also been found in males with severe brain dysfunction (neonatal encephalopathy) who live only into early childhood. In addition, several people with features of both Rett syndrome and Angelman syndrome (a condition characterized by mental retardation, problems with movement, and inappropriate laughter and excitability) have mutations in the MECP2 gene. Lastly, MECP2 mutations or changes in the gene's activity have been reported in some cases of autism (a developmental disorder that affects communication and social interaction).

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• Ensembl Gene ref Protein ref
• GeneCard
• RettBASE: IRSA MECP2 Variation Database