MECP2 Gene and Rett Syndrome: Mutations and Clinical Trials

The MECP2 gene sits on chromosome Xq28, and its full name is methyl-CpG binding protein 2. Orphanet links MECP2 to 7 rare conditions and lists variants in the gene as a cause of 5 of them. Trial Friend's Rett Syndrome page lists MECP2 among the genes behind the condition. As of September 29, 2026, 12 recruiting or soon-opening trials on ClinicalTrials.gov name MECP2 as a gene.

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What the MECP2 gene does

MECP2 makes the MeCP2 protein, which helps control when other genes are active. It is especially plentiful in brain cells, where it appears to help maintain the connections between nerve cells.

Summarized from the MECP2 page on MedlinePlus Genetics, U.S. National Library of Medicine, checked September 29, 2026.

MECP2 and Rett Syndrome

These condition pages list MECP2 among the genes behind the condition, checked against genetics references when each page was written.

Rett Syndrome

The gene is on the X chromosome, and one variant can cause the condition in males or females. Most cases are new variants rather than inherited.

More than 99% of cases have no family history; CDKL5 and FOXG1 disorders were once called Rett variants but are now classed separately.

MECP2 mutation clinical trials

These recruiting or soon-opening trials mention MECP2 as a gene in their title, summary, eligibility rules or keywords. Some want people with a variant in it, and others study it more broadly, which is why each trial's own words are shown. In cancer trials the gene change is usually one found in the tumor rather than one a person inherited.

12 trials, checked September 29, 2026. The list refreshes from ClinicalTrials.gov every few hours.

RecruitingNCT07569445
Auditory EEG and Behavioral Assessments in Individuals With Rett Syndrome
Rett Syndrome
Why it's listed: “Have a pathogenic MECP2 genetic variant confirmed via genetic testing”
RecruitingNCT05740761
Gene Editing as a Therapeutic Approach for Rett Syndrome
Rett Syndrome
Why it's listed: “…as9-based gene editing combined with AAV-based delivery for correction of the most common MECP2 mutations both in vitro and in vivo.”
RecruitingNCT05432349
Rett Syndrome Registry
Rett Syndrome · Rett Syndrome, Atypical · Genetic Disease
Why it's listed: “The Rett Syndrome Registry is a longitudinal observational study of individuals with MECP2 mutations and a diagnosis of Rett syndrome. Designed together with the IRSF Rett Syndrome Center of…”
RecruitingNCT06615206
A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)
MECP2 Duplication Syndrome
Why it's listed: “…tral nervous system development and functional maintenance, which gain-of-function causes MECP2 duplication syndrome (MDS). Affecting primarily in males, this disorder is characterized by severe in…”
RecruitingPhase 3NCT06840496
To Investigate the Efficacy of Treatment With Oral NA-921 (Bionetide) Versus Placebo in Females With Rett Syndrome
Rett Syndrome
Why it's listed: “Has a documented disease-causing mutation in the MECP2 gene”
RecruitingPhase 1, Phase 2NCT06430385
ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)
Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
Why it's listed: “Participant has a documented diagnosis of MDS with genetic confirmation of MECP2 duplication.”
RecruitingNCT06585605
A Retrospective Survey-based Multicenter Study to Delineate the Molecular and Phenotypic Spectrum of Epilepsy-dyskinesia Syndromes
Epilepsy in Children · Dyskinesias · Movement Disorders in Children
Why it's listed: Lists MECP2 among its conditions or keywords
RecruitingPhase 2NCT07430046
Repurposing Mirtazapine in Rett Syndrome
RETT Syndrome With Proven MECP2 Mutation
Why it's listed: “Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused by an MECP2 gene mutation on the X chromosome, primarily affecting females. It causes progressive motor and cogniti…”
RecruitingNCT04900493
The Rett Syndrome Global Registry
Rett Syndrome
Why it's listed: “…uals of any age, living or deceased, must have a diagnosis of Rett syndrome and/or have a mutation in MECP2.”
RecruitingNCT06967727
Registry and Natural History of Epilepsy-Dyskinesia Syndromes
Epilepsy-Dyskinesia · Epilepsy · Dyskinesia
Why it's listed: Lists MECP2 among its conditions or keywords
RecruitingNCT05932589
Neurophysiologic Biomarkers in Rett Syndrome
Rett Syndrome · RTT · Rett Syndrome, Atypical
Why it's listed: “Likely Rett Group: Females from 1 year to \< 5 years of age with MECP2 variant if regression has not yet occurred or child is within 6 months of last skill loss.”
Opening soonPhase 2, Phase 3NCT07257978
Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
RETT Syndrome With Proven MECP2 Mutation · Rett Syndrome
Why it's listed: “Classical/typical RTT as confirmed with a documented pathogenic variant in the MECP2 gene”

All conditions linked to MECP2 gene mutations

Orphanet records how each gene relates to each condition. Orphanet links MECP2 to 7 rare conditions and lists variants in the gene as a cause of 5 of them.

  • Causes it. Disease-causing variants in this gene are a direct cause of the condition.
  • Plays a part. Orphanet lists the gene as shaping the condition, often as one of several genes in a missing or extra piece of a chromosome.
  • Raises risk. Some variants raise the chance of the condition without guaranteeing it.
Atypical Rett syndromeCauses itTrial Friend pageOrphanet
Rett syndromeCauses itTrial Friend pageOrphanet
MECP2-related severe neonatal encephalopathyCauses itOrphanet
X-linked intellectual disability-psychosis-macroorchidism syndromeCauses itOrphanet
X-linked non-syndromic intellectual disabilityCauses itOrphanet
Proximal Xq28 duplication syndromePlays a partOrphanet
Systemic lupus erythematosusRaises riskOrphanet

MECP2 genetic test results and what a variant can mean

Labs sort each variant they find into 5 groups, from pathogenic and likely pathogenic through uncertain significance to likely benign and benign. Only the first 2 are usually treated as the cause of a condition. A variant of uncertain significance, or VUS, is one without enough evidence either way yet, and labs can reclassify it as research builds.

A genetic counselor or your doctor can explain what a specific result means for you and your family. Our genetic testing guide covers the terms, and MedlinePlus Genetics from the National Library of Medicine has a plain-language page on MECP2.

MECP2 gene questions

What does the MECP2 gene do?

MECP2 makes the MeCP2 protein, which helps control when other genes are active. It is especially plentiful in brain cells, where it appears to help maintain the connections between nerve cells. This summary follows MedlinePlus Genetics from the U.S. National Library of Medicine.

Are there clinical trials for people with MECP2 gene variants?

As of September 29, 2026, 12 recruiting or soon-opening trials on ClinicalTrials.gov name MECP2 as a gene. Each one is listed on this page with the words from the trial that mention the gene. ClinicalTrials.gov also lists 17 open trials for Rett Syndrome, and Match Me on Trial Friend can check those against age, sex, location and treatment history.

What conditions are linked to the MECP2 gene?

Orphanet links MECP2 to 7 rare conditions and lists variants in the gene as a cause of 5 of them. They include Atypical Rett syndrome, Rett syndrome, MECP2-related severe neonatal encephalopathy, X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked non-syndromic intellectual disability, Proximal Xq28 duplication syndrome and 1 more. Orphanet is the European rare disease database run by INSERM in Paris.

How is Rett Syndrome inherited?

The inheritance pattern is X-linked dominant, usually de novo. The gene is on the X chromosome, and one variant can cause the condition in males or females. Most cases are new variants rather than inherited. More than 99% of cases have no family history; CDKL5 and FOXG1 disorders were once called Rett variants but are now classed separately.

What does an MECP2 variant of uncertain significance mean?

A variant of uncertain significance, or VUS, is a change in the gene that labs don't yet have enough evidence to call disease-causing or harmless. It is not used on its own to diagnose a condition, and labs can reclassify it as research builds. A genetic counselor can explain what a specific result means for you and your family.

Sources

  • Gene and condition links from Orphadata (Orphanet, INSERM US14), used under CC BY 4.0, read September 29, 2026.
  • Trials from ClinicalTrials.gov, read September 29, 2026.
  • MECP2 gene, MedlinePlus Genetics, U.S. National Library of Medicine.
  • Inheritance and gene notes from the Trial Friend condition pages above, each checked against genetics references.

Other gene pages

The gene search covers every gene Orphanet links to a rare disease.