MECP2
Chr XX-linkedXLRXLDmethyl-CpG binding protein 2
Also known as: AUTSX3, MRX16, MRX79, MRXS13, MRXSL, PPMX, RS, RTS
MECP2 encodes a methyl-CpG binding protein that binds specifically to methylated DNA and represses transcription from methylated gene promoters, playing an essential role in embryonic development. Mutations cause Rett syndrome and its variants, X-linked intellectual disability syndromes, neonatal severe encephalopathy, and autism susceptibility, with inheritance patterns including X-linked dominant (typical in Rett syndrome) and X-linked recessive forms. The gene shows high constraint against loss-of-function variants, and mutations predominantly cause disease through loss-of-function mechanisms, though the clinical phenotype varies significantly based on the specific variant and X-inactivation patterns.
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
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
498 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 81 | 4 | 57 | 0 | 142 |
Likely Pathogenic | 35 | 14 | 1 | 0 | 50 |
VUS | 9 | 131 | 27 | 4 | 171 |
Likely Benign | 0 | 8 | 31 | 55 | 94 |
Benign | 0 | 2 | 8 | 2 | 12 |
Conflicting | — | 3 | |||
| Total | 125 | 159 | 124 | 61 | 472 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
International CDKL5 Clinical Research Network
RECRUITINGGene Editing as a Therapeutic Approach for Rett Syndrome
RECRUITINGSafety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study)
ACTIVE NOT RECRUITINGA Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
RECRUITINGRepurposing Mirtazapine in Rett Syndrome
RECRUITINGEfficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
NOT YET RECRUITINGPrecision Medicine in the Treatment of Epilepsy
RECRUITINGA Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study)
RECRUITINGAn Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome
RECRUITINGRett REVOLUTION Trial: An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Rett Syndrome
RECRUITINGSafety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome
NOT YET RECRUITINGGROWing Up With Rare GENEtic Syndromes
RECRUITINGExternal Resources
Links to major genomics databases and tools