MECP2
methyl-CpG binding protein 2, the group of Methyl-CpG binding domain containing
Basic information
Region (hg38): X:154021572-154137103
Previous symbols: [ "RTT", "MRX16", "MRX79" ]
Links
Phenotypes
GenCC
Source:
- Rett syndrome (Definitive), mode of inheritance: XLD
- syndromic X-linked intellectual disability Lubs type (Definitive), mode of inheritance: XLR
- X-linked intellectual disability-psychosis-macroorchidism syndrome (Definitive), mode of inheritance: XLR
- chromosome Xq28 duplication syndrome (Definitive), mode of inheritance: XLR
- severe neonatal-onset encephalopathy with microcephaly (Definitive), mode of inheritance: XLR
- Rett syndrome (Definitive), mode of inheritance: XL
- Rett syndrome (Supportive), mode of inheritance: XL
- X-linked intellectual disability-psychosis-macroorchidism syndrome (Supportive), mode of inheritance: XL
- atypical Rett syndrome (Supportive), mode of inheritance: AD
- non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
- severe neonatal-onset encephalopathy with microcephaly (Supportive), mode of inheritance: XL
- Rett syndrome (Definitive), mode of inheritance: XL
- syndromic X-linked intellectual disability Lubs type (Definitive), mode of inheritance: XL
- chromosome Xq28 duplication syndrome (Definitive), mode of inheritance: XL
- severe neonatal-onset encephalopathy with microcephaly (Definitive), mode of inheritance: XL
- Rett syndrome (Strong), mode of inheritance: XL
- Rett syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Rett syndrome | XL | Neurologic | Medical management (with trofinetide) has been shown to be beneficial related to neurological outcomes | Neurologic | 5300597; 8651288; 9377804; 9326329; 9637791; 10508514; 10232754; 10398236; 10577905; 10986043; 11106359; 12615169; 11071498; 11022934; 11768391; 11309367; 11402105; 11746022; 11913564; 11930274; 11807877; 11885030; 12325019; 12615169; 12770674; 14598336; 12615169; 12615169; 15034579; 16077729; 15689435; 16080119; 17172942; 16965328; 17088400; 16690727; 16832102; 17712354; 17351020; 18477000; 18989701; 19194883; 18985075; 19365833; 20035514; 20425814; 21154482; 21104896; 22415763; 22578097; 22581587; 28964591; 30918097 |
ClinVar
This is a list of variants' phenotypes submitted to
- Severe neonatal-onset encephalopathy with microcephaly (757 variants)
- Rett syndrome (621 variants)
- not provided (543 variants)
- not specified (257 variants)
- Inborn genetic diseases (138 variants)
- X-linked intellectual disability-psychosis-macroorchidism syndrome (54 variants)
- Autism, susceptibility to, X-linked 3 (37 variants)
- History of neurodevelopmental disorder (23 variants)
- MECP2-related condition (17 variants)
- Intellectual disability (14 variants)
- Neurodevelopmental delay (10 variants)
- See cases (9 variants)
- Angelman syndrome (9 variants)
- Syndromic X-linked intellectual disability Lubs type (8 variants)
- Autism, susceptibility to, X-linked 3;Rett syndrome;X-linked intellectual disability-psychosis-macroorchidism syndrome;Severe neonatal-onset encephalopathy with microcephaly;Syndromic X-linked intellectual disability Lubs type (7 variants)
- Rett syndrome;Syndromic X-linked intellectual disability Lubs type;Autism, susceptibility to, X-linked 3;Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome (7 variants)
- - (5 variants)
- MECP2-Related Disorders (4 variants)
- Syndromic X-linked intellectual disability Lubs type;Rett syndrome;Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3 (4 variants)
- Rett syndrome, zappella variant (4 variants)
- X-linked intellectual disability-psychosis-macroorchidism syndrome;Severe neonatal-onset encephalopathy with microcephaly;Autism, susceptibility to, X-linked 3;Syndromic X-linked intellectual disability Lubs type;Rett syndrome (3 variants)
- Encephalopathy, neonatal severeMental retardation, X-linked, syndromic 13Rett syndrome (3 variants)
- Developmental disorder (3 variants)
- Abnormality of the nervous system (3 variants)
- Rett syndrome;X-linked intellectual disability-psychosis-macroorchidism syndrome (2 variants)
- Severe neonatal-onset encephalopathy with microcephaly;Rett syndrome;Syndromic X-linked intellectual disability Lubs type;X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3 (2 variants)
- Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome;Rett syndrome;Autism, susceptibility to, X-linked 3;Syndromic X-linked intellectual disability Lubs type (2 variants)
- Neurodevelopmental disorder (2 variants)
- Syndromic X-linked intellectual disability Lubs type;X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3;Severe neonatal-onset encephalopathy with microcephaly;Rett syndrome (2 variants)
- Atypical Rett syndrome (2 variants)
- Attention deficit hyperactivity disorder (2 variants)
- Syndromic X-linked intellectual disability Lubs type;Rett syndrome;Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome (2 variants)
- Syndromic X-linked intellectual disability Lubs type;X-linked intellectual disability-psychosis-macroorchidism syndrome (2 variants)
- Autism spectrum disorder (2 variants)
- X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3;Syndromic X-linked intellectual disability Lubs type;Rett syndrome;Severe neonatal-onset encephalopathy with microcephaly (1 variants)
- Rett syndrome;Syndromic X-linked intellectual disability Lubs type;Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome (1 variants)
- Global developmental delay;Developmental regression (1 variants)
- Seizure (1 variants)
- X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3;Severe neonatal-onset encephalopathy with microcephaly;Syndromic X-linked intellectual disability Lubs type;Rett syndrome (1 variants)
- Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3;Syndromic X-linked intellectual disability Lubs type;Rett syndrome (1 variants)
- Severe neonatal-onset encephalopathy with microcephaly;Syndromic X-linked intellectual disability Lubs type;Rett syndrome;X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3 (1 variants)
- Rett syndrome;Syndromic X-linked intellectual disability Lubs type (1 variants)
- MECP2-Related Disorder (1 variants)
- Angelman syndrome;X-linked intellectual disability-psychosis-macroorchidism syndrome;Rett syndrome (1 variants)
- Atypical behavior (1 variants)
- Schizophrenia (1 variants)
- Delayed gross motor development;Loss of ambulation;Delayed speech and language development (1 variants)
- Syndromic X-linked intellectual disability Lubs type;Autism, susceptibility to, X-linked 3;X-linked intellectual disability-psychosis-macroorchidism syndrome;Rett syndrome;Severe neonatal-onset encephalopathy with microcephaly (1 variants)
- 8 conditions (1 variants)
- Smith-Magenis Syndrome-like (1 variants)
- Autism, susceptibility to, X-linked 3;Severe neonatal-onset encephalopathy with microcephaly;X-linked intellectual disability-psychosis-macroorchidism syndrome;Rett syndrome;Syndromic X-linked intellectual disability Lubs type (1 variants)
- Seizure;Absent speech;Irregular respiration;Severe global developmental delay;Developmental regression (1 variants)
- Epileptic encephalopathy (1 variants)
- Focal epilepsy (1 variants)
- Intellectual disability;Seizure (1 variants)
- X-linked intellectual disability-psychosis-macroorchidism syndrome;Autism, susceptibility to, X-linked 3;Rett syndrome;Syndromic X-linked intellectual disability Lubs type;Severe neonatal-onset encephalopathy with microcephaly (1 variants)
- Severe underweight in infancy childhood and adolescence;Microcephaly;Intellectual disability;Psychomotor retardation (1 variants)
- Bruxism;Delayed gross motor development;Stereotypic movement disorder;Delayed speech and language development (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MECP2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 191 | 29 | 230 | |||
| missense | 34 | 64 | 232 | 77 | 54 | 461 |
| nonsense | 40 | 13 | 55 | |||
| start loss | 3 | |||||
| frameshift | 206 | 85 | 10 | 301 | ||
| inframe indel | 57 | 14 | 90 | |||
| splice donor/acceptor (+/-2bp) | 10 | 12 | ||||
| splice region ? | 1 | 1 | 5 | 6 | 4 | 17 |
| non coding ? | 20 | 52 | 44 | 117 | ||
| Total | 298 | 172 | 331 | 334 | 134 |
Highest pathogenic variant AF is 0.0000609
Variants in MECP2
This is a list of pathogenic ClinVar variants found in the MECP2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MECP2 | protein_coding | protein_coding | ENST00000453960 | 3 | 76189 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.894 | 0.106 | 125098 | 3 | 6 | 125107 | 0.0000360 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -1.21 | 281 | 229 | 1.23 | 0.0000208 | 3187 |
| Missense in Polyphen | 43 | 80.097 | 0.53685 | 1003 | ||
| Synonymous | -7.95 | 196 | 96.6 | 2.03 | 0.00000908 | 1067 |
| Loss of Function | 2.89 | 1 | 11.7 | 0.0858 | 0.00000111 | 209 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000158 | 0.000135 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000738 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000643 | 0.0000354 |
| Middle Eastern | 0.0000738 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000228 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC). {ECO:0000250|UniProtKB:Q9Z2D6}.;
- Disease
- DISEASE: Angelman syndrome (AS) [MIM:105830]: A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue. {ECO:0000269|PubMed:11283202}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, X-linked, syndromic, 13 (MRXS13) [MIM:300055]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS13 patients manifest mental retardation associated with other variable features such as spasticity, episodes of manic depressive psychosis, increased tone and macroorchidism. {ECO:0000269|PubMed:10986043, ECO:0000269|PubMed:11007980, ECO:0000269|PubMed:11309367, ECO:0000269|PubMed:11805248, ECO:0000269|PubMed:11885030, ECO:0000269|PubMed:12161600, ECO:0000269|PubMed:12325019, ECO:0000269|PubMed:12615169, ECO:0000269|PubMed:16966553, ECO:0000269|PubMed:17296936}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Rett syndrome (RTT) [MIM:312750]: An X-linked dominant neurodevelopmental disorder, and one of the most common causes of mental retardation in females. Patients appear to develop normally until 6 to 18 months of age, then gradually lose speech and purposeful hand movements, and develop microcephaly, seizures, autism, ataxia, mental retardation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. {ECO:0000269|PubMed:10508514, ECO:0000269|PubMed:10577905, ECO:0000269|PubMed:10745042, ECO:0000269|PubMed:10767337, ECO:0000269|PubMed:10814719, ECO:0000269|PubMed:10944854, ECO:0000269|PubMed:10991688, ECO:0000269|PubMed:10991689, ECO:0000269|PubMed:11055898, ECO:0000269|PubMed:11241840, ECO:0000269|PubMed:11269512, ECO:0000269|PubMed:11283202, ECO:0000269|PubMed:11376998, ECO:0000269|PubMed:11402105, ECO:0000269|PubMed:11706982, ECO:0000269|PubMed:11738883, ECO:0000269|PubMed:12161600, ECO:0000269|PubMed:12567420, ECO:0000269|PubMed:12966522, ECO:0000269|PubMed:12966523, ECO:0000269|PubMed:15034579, ECO:0000269|PubMed:15057977, ECO:0000269|PubMed:17296936, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28348241}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Autism, X-linked 3 (AUTSX3) [MIM:300496]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:12770674}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Encephalopathy, neonatal severe, due to MECP2 mutations (ENS-MECP2) [MIM:300673]: A neurodevelopmental disorder characterized by severe neonatal encephalopathy, developmental delay, mental retardation, microcephaly, seizures. Additional features include respiratory insufficiency and central hypoventilation, gastroesophageal reflux, axial hypotonia, hyperreflexia and dyskinetic movements. {ECO:0000269|PubMed:11238684}. Note=The disease is caused by mutations affecting the gene represented in this entry. The MECP2 gene is mutated in Rett syndrome, a severe neurodevelopmental disorder that almost always occurs in females. Although it was first thought that MECP2 mutations causing Rett syndrome were lethal in males, later reports identified a severe neonatal encephalopathy in surviving male sibs of patients with Rett syndrome. Additional reports have confirmed a severe phenotype in males with Rett syndrome-associated MECP2 mutations.; DISEASE: Mental retardation, X-linked, syndromic, Lubs type (MRXSL) [MIM:300260]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSL patients manifest mental retardation associated with variable features. They include swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections, hypotonia, mild myopathy and characteristic facies such as downslanting palpebral fissures, hypertelorism and a short nose with a low nasal bridge. {ECO:0000269|PubMed:16080119}. Note=The disease is caused by mutations affecting the gene represented in this entry. Increased dosage of MECP2 due to gene duplication appears to be responsible for the mental retardation phenotype.;
- Pathway
- Ectoderm Differentiation;MECP2 and Associated Rett Syndrome;Lung fibrosis;HDAC6 interactions;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
(Consensus)
Recessive Scores
- pRec
- 0.694
Intolerance Scores
- loftool
- 0.00365
- rvis_EVS
- -0.89
- rvis_percentile_EVS
- 10.46
Haploinsufficiency Scores
- pHI
- 0.439
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.529
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mecp2
- Phenotype
- vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- mecp2
- Affected structure
- neutrophil
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;behavioral fear response;response to hypoxia;startle response;neurological system process involved in regulation of systemic arterial blood pressure;regulation of respiratory gaseous exchange by neurological system process;inositol metabolic process;mitochondrial electron transport, ubiquinol to cytochrome c;chromatin silencing;regulation of gene expression by genetic imprinting;transcription initiation from RNA polymerase II promoter;glutamine metabolic process;cellular biogenic amine metabolic process;mitotic spindle organization;synapse assembly;respiratory gaseous exchange;long-term memory;protein localization;glucocorticoid metabolic process;positive regulation of cell population proliferation;adult locomotory behavior;visual learning;response to radiation;pathogenesis;post-embryonic development;negative regulation of gene expression;positive regulation of G2/M transition of mitotic cell cycle;dendrite development;negative regulation of angiogenesis;histone methylation;histone acetylation;proprioception;sensory perception of pain;cerebellum development;ventricular system development;negative regulation of histone methylation;cardiolipin metabolic process;negative regulation of histone acetylation;social behavior;neuron maturation;negative regulation of neuron apoptotic process;negative regulation of blood vessel endothelial cell migration;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;phosphatidylcholine metabolic process;catecholamine secretion;negative regulation of smooth muscle cell differentiation;positive regulation of synapse assembly;excitatory postsynaptic potential;long-term synaptic potentiation;positive regulation of microtubule nucleation;positive regulation of histone H3-K9 trimethylation;positive regulation of DNA methylation;negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation
- Cellular component
- chromatin;heterochromatin;extracellular space;nucleus;nucleoplasm;mitochondrion;centrosome;cytosol;postsynapse
- Molecular function
- DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;transcription corepressor activity;RNA binding;mRNA binding;protein binding;transcription factor binding;methyl-CpG binding;double-stranded methylated DNA binding;protein domain specific binding;siRNA binding;protein N-terminus binding