MECP2 (Methyl-CpG-Binding Protein 2): A Master Regulator of Gene Expression in Rett Syndrome and Beyond
Explore the genomic architecture, function, disease associations, expression patterns, and mutation landscape of the MECP2 gene, a critical epigenetic regulator implicated in neurodevelopmental disorders and various cancers.
Gene Information Card
| Symbol | MECP2 |
|---|---|
| Full Name | Methyl-CpG-binding protein 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 4204 ncbi.nlm.nih.gov/gene/4204 |
| Ensembl ID | ENSG00000169057 |
| UniProt ID | P51608 |
| OMIM ID | 300005 |
| HGNC ID | 6990 |
| Aliases | RTT, RS, MRXSL, AUTSX3, MRX79, PPMX, DKFZp686A24160 |
Description
The MECP2 gene encodes methyl-CpG-binding protein 2, a critical epigenetic reader that binds to methylated DNA and regulates gene expression. It is essential for normal neurological function, particularly in mature neurons, and its mutations lead to Rett syndrome, a severe neurodevelopmental disorder. MECP2 also plays roles in cancer, where its expression can be altered, affecting tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rett syndrome | Loss-of-function mutations in MECP2 lead to reduced protein function, causing abnormal neuronal maturation and synaptic function. | ClinVar, OMIM |
| MECP2 duplication syndrome | Increased dosage of MECP2 due to genomic duplications results in overexpression, leading to intellectual disability and motor dysfunction. | ClinVar, OMIM |
| Autism spectrum disorder | MECP2 variants, including missense mutations, have been associated with autism, likely through altered epigenetic regulation of neuronal genes. | ClinVar, OMIM |
| Breast cancer | MECP2 overexpression in certain breast cancer subtypes may promote tumor growth by silencing tumor suppressor genes. | COSMIC, PubMed |
| Colorectal cancer | MECP2 expression is altered in colorectal cancer, potentially affecting cell proliferation and apoptosis. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Highest expression in brain, especially in neurons. |
| Lung | Low | Low expression. |
| Liver | Low | Low expression. |
| Kidney | Low | Low expression. |
| Heart | Low | Low expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line, high MECP2 expression. |
| HeLa (cervical cancer) | Medium | Moderate expression. |
| MCF7 (breast cancer) | High | Overexpressed in some breast cancer lines. |
| HCT116 (colorectal cancer) | Medium | Moderate expression. |
| HEK293 (embryonic kidney) | Medium | Moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R168X | Nonsense | Common in Rett syndrome (~10% of cases) | Truncated protein, loss of function. |
| T158M | Missense | Common in Rett syndrome (~8% of cases) | Disrupts methyl-CpG binding domain, reduced function. |
| R255X | Nonsense | Common in Rett syndrome (~5% of cases) | Truncated protein, loss of function. |
| R306C | Missense | Common in Rett syndrome (~5% of cases) | Affects transcriptional repression domain, partial loss of function. |
| C-terminal deletions | Deletion | Variable frequency | Impair protein stability and function. |
Mutation functional classification
Loss of Function (LOF)
Most Rett syndrome mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects, resulting in reduced MECP2 activity.
Gain of Function (GOF)
MECP2 duplication syndrome is a gain-of-function condition due to increased gene dosage, causing overexpression and aberrant gene silencing.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner, interfering with the function of the wild-type protein in heterozygous females.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • Chromatin binding |
| • Transcription factor binding | • Regulation of transcription by RNA polymerase II |
| • Chromatin organization | • Nervous system development |
| • Synaptic transmission | • Response to DNA damage stimulus |
Pathways
• Epigenetic regulation of gene expression
• Transcriptional regulation by MECP2
• Neuronal development and function
• DNA methylation-dependent gene silencing
Protein Summary
MECP2 is a multifunctional protein that binds to methylated CpG dinucleotides and recruits co-repressor complexes to silence gene transcription. It is highly expressed in neurons, where it regulates the expression of genes involved in synaptic plasticity and neuronal maturation. MECP2 also interacts with histone deacetylases and other chromatin remodelers, playing a central role in epigenetic regulation. Mutations in MECP2 disrupt these functions, leading to severe neurodevelopmental phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MECP2 Knockout HEK293 Cell Line | EDJ-KQ3378 | Human | 4204 | Details Get a Quote |
| MECP2 Knockout A-549 Cell Line | EDJ-KQ25062 | Human | 4204 | Details Get a Quote |
| MECP2 Knockout HCT 116 Cell Line | EDJ-KQ25063 | Human | 4204 | Details Get a Quote |
| MECP2 Knockout HeLa Cell Line | EDJ-KQ25064 | Human | 4204 | Details Get a Quote |
| Mecp2 Knockout 3T3-Swiss albino Cell Line | EDJ-KZ347 | Mouse | 4204 | Details Get a Quote |
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