MECP2
Chr XX-linkedXLRXLDmethyl-CpG binding protein 2
Also known as: AUTSX3, MRX16, MRX79, MRXS13, MRXSL, PPMX, RS, RTS
DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
This gene — mechanism propensity
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MECP2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
ACTIVE NOT RECRUITINGRett REVOLUTION Trial: An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Rett Syndrome
RECRUITINGAn Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome
RECRUITINGInternational CDKL5 Clinical Research Network
RECRUITINGGCB-002 in Treatment of Patients With Rett Syndrome
ENROLLING BY INVITATIONEfficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
NOT YET RECRUITINGSafety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome
RECRUITINGSingle-Dose AAV-MECP2 Safety/Tolerability and Efficacy in Rett Syndrome
ACTIVE NOT RECRUITINGRepurposing Mirtazapine in Rett Syndrome
RECRUITINGA Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study)
ACTIVE NOT RECRUITINGRett Syndrome Registry
RECRUITINGSafety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools