MECP2 and associated Rett syndrome (WP3584)

Homo sapiens

MECP2 (methyl-CpG binding protein 2) is in many mammals an important regulator of neuronal function and development. It affects all cell types, especially neurons but also astrocytes, oligodendrocytes, and glial cells. MECP2 plays an important role in neuronal differentiation, maturation, morphology and function and influences synaptic plasticity. Mutations impairing the proper function of MECP2 are mainly associated with the Rett syndrome but may also contribute to other neurological disorders like schizophrenia, FASD (fetal alcohol syndrome), PPM-X-syndrome, autism, Prader-Will-syndrome, and Angelman-syndrome. Dependant on the cofactors MECP2 acts as an activator or repressor of transcription and micro RNA production. It affects RNA splicing and regulates chromatin structure together with HP1 and interferes in methylation of DNA (epigenetics). The expression of MECP2 itself is highly regulated by promotor elements, cis-regulatory elements, polyadenylation, promotor DNA methylation and miRNA. Please cite this pathways as: Ehrhart et al. 2016 - the pathway version in the paper is 90609. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]
last edited


Friederike Ehrhart , Egon Willighagen , Kristina Hanspers , Ryan Miller , Martina Summer-Kutmon , Alex Pico , Lauren J. Dupuis , and Eric Weitz

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Homo sapiens


Diseases Rare Diseases


Pathway Ontology: disease pathway

Disease Ontology: Rett syndrome


Label Type Compact Identifier Comment
Dopamine Metabolite hmdb:HMDB0000073
GABA Metabolite chebi:16865
Glycine Metabolite hmdb:HMDB0000123
Norepinephrine Metabolite hmdb:HMDB0000216
Norepinephrine Metabolite hmdb:HMDB0000216
NMDA Metabolite hmdb:HMDB0002393 N-Methyl-D-aspartic acid
Glutamate Metabolite chebi:29987
Serotonin Metabolite hmdb:HMDB0000259
Trofinetide Metabolite pubchem.compound:11318905
Dopamine Metabolite hmdb:HMDB0000073
Melatonin Metabolite hmdb:HMDB0001389
Serotonin Metabolite hmdb:HMDB0000259
Myoinositol Metabolite hmdb:HMDB0000211
Glutamate Metabolite chebi:29987
GABA Metabolite chebi:16865
Glutamate Metabolite chebi:29987
GABA Metabolite chebi:16865
D-serine Metabolite chebi:16523
NCOR1 GeneProduct ensembl:ENSG00000141027 nuclear receptor co-repressor 1
MYT1 GeneProduct ensembl:ENSG00000196132 myelin transcription factor 1
proof of Mecp2 inhibition in Oligodendrocytes
BRN3 GeneProduct ensembl:ENSG00000152192 POU domain, class 4, transcription factor 1
DLX5 GeneProduct ensembl:ENSG00000105880
MTOR GeneProduct ensembl:ENSG00000198793
APOC2 GeneProduct ensembl:ENSG00000234906 apolipoprotein C-II
HDAC1 GeneProduct ensembl:ENSG00000116478
BDNF GeneProduct ensembl:ENSG00000176697 brain derived neurotrophic factor
SST GeneProduct ensembl:ENSG00000157005 Somatostatin
NREP GeneProduct ensembl:ENSG00000134986 neuronal regeneration related protein
TET3 GeneProduct ensembl:ENSG00000187605
MECP2 GeneProduct ensembl:ENSG00000169057 methyl CpG binding protein 2
BRN2 GeneProduct ensembl:ENSG00000184486 POU domain, class 3, transcription factor 2
DLX6 GeneProduct ensembl:ENSG00000006377
SMC3 GeneProduct ensembl:ENSG00000108055 tructural maintenance of chromosomes 3
MEF2C GeneProduct ensembl:ENSG00000081189 myocyte enhancer factor 2C
TAP1 GeneProduct ensembl:ENSG00000168394 transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
UBE3A GeneProduct ensembl:ENSG00000114062
RBFOX1 GeneProduct ensembl:ENSG00000078328 ataxin 2 binding protein 1, Rbfox1
CNP GeneProduct ensembl:ENSG00000173786 2',3'-cyclic nucleotide 3' phosphodiesterase
TET2 GeneProduct ensembl:ENSG00000168769
SGK1 GeneProduct ensembl:ENSG00000118515
FKBP5 GeneProduct ensembl:ENSG00000096060
RPS6 GeneProduct ensembl:ENSG00000137154
EZH2 GeneProduct ensembl:ENSG00000106462 histone H3 lysine 27 methyltransferase
GAMT GeneProduct ensembl:ENSG00000130005 guanidinoacetate methyltransferase
AKT1 GeneProduct ensembl:ENSG00000142208
MPP1 GeneProduct ensembl:ENSG00000130830
OPRK1 GeneProduct ensembl:ENSG00000082556 opioid receptor, kappa 1
ARHGEF26 GeneProduct ensembl:ENSG00000114790 Rho guanine nucleotide exchange factor (GEF) 26
SIN3A GeneProduct ensembl:ENSG00000169375
IGF2 GeneProduct ensembl:ENSG00000167244
SP1 GeneProduct ensembl:ENSG00000185591 trans-acting transcription factor 1
GAD1 GeneProduct ensembl:ENSG00000128683
TAF1 GeneProduct ensembl:ENSG00000147133 TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor
HNRNPH1 GeneProduct ensembl:ENSG00000169045 HNRNPH1
CSRP1 GeneProduct ensembl:ENSG00000159176 cysteine and glycine-rich protein 1
GRID1 GeneProduct ensembl:ENSG00000182771
CDON GeneProduct ensembl:ENSG00000064309 cell adhesion molecule-related/down-regulated by oncogenes
MYT1 GeneProduct ensembl:ENSG00000196132 Myelin transcription factor 1
C/EBP GeneProduct ensembl:ENSG00000221869 CCAAT/enhancer binding protein (Cebpd), delta
CAMK2A GeneProduct ensembl:ENSG00000070808
MBP GeneProduct ensembl:ENSG00000197971 myelin basic protein
BCL6 GeneProduct ensembl:ENSG00000113916 B cell leukemia/lymphoma 6
GABRR2 GeneProduct ensembl:ENSG00000111886 gamma-aminobutyric acid (GABA) C receptor, subunit rho 2
CTCF GeneProduct ensembl:ENSG00000102974 CCCTC-binding factor
SP3 GeneProduct ensembl:ENSG00000172845 trans-acting transcription factor 3
PRPF3 GeneProduct ensembl:ENSG00000134748 PRP3 pre-mRNA processing factor 3 homolog (yeast)
E2F1 GeneProduct ensembl:ENSG00000101412 E2F transcription factor 1
AMPA GeneProduct ensembl:ENSG00000155511 Glutamate receptor
REST GeneProduct ensembl:ENSG00000084093 RE1-silencing transcription factor
Silences Mecp2 in non-neuronal tissue
MAG GeneProduct ensembl:ENSG00000105695 myelin-associated glycoprotein
GPRIN1 GeneProduct ensembl:ENSG00000169258 G protein-regulated inducer of neurite outgrowth 1
TET1 GeneProduct ensembl:ENSG00000138336 tet methylcytosine dioxygenase 1
IGF1R GeneProduct ensembl:ENSG00000140443
HNRNPF GeneProduct ensembl:ENSG00000169813 Hnrnpf
heterogeneous nuclear ribonucleoprotein F
YB1 GeneProduct ensembl:ENSG00000065978 data obtained with human cell line and mouse primary tissue
Y box protein 1
MECP2 GeneProduct ensembl:ENSG00000169057 methyl CpG binding protein 2
MECP2 GeneProduct ensembl:ENSG00000169057 methyl CpG binding protein 2
SP1 GeneProduct ensembl:ENSG00000185591 trans-acting transcription factor 1
CREB1 GeneProduct ensembl:ENSG00000118260
RPS6 GeneProduct ensembl:ENSG00000137154
BDNF GeneProduct ensembl:ENSG00000176697 brain derived neurotrophic factor
GAMT GeneProduct ensembl:ENSG00000130005 guanidinoacetate methyltransferase
MECP2 GeneProduct ensembl:ENSG00000169057 methyl CpG binding protein 2
IGF1 GeneProduct ensembl:ENSG00000017427 Glutamate receptor
FOXG1 GeneProduct ensembl:ENSG00000176165 Glutamate receptor
PTEN GeneProduct ensembl:ENSG00000171862
DHX9 GeneProduct ensembl:ENSG00000135829 binding to MECP2 confirmed in mice
FUS GeneProduct ensembl:ENSG00000089280 binding to MECP2 confirmed in mice
HNRNPF GeneProduct ensembl:ENSG00000169813 binding to MECP2 confirmed in mice
also known as hnRNPH+F
TARDBP GeneProduct ensembl:ENSG00000120948 binding to MECP2 confirmed in mice
also known as TDP-43
PSIP1 GeneProduct ensembl:ENSG00000164985 binding to MECP2 confirmed in mice
also known as LEDGF
FUT8 GeneProduct ensembl:ENSG00000033170 fucosyltransferase 8
FGF2 GeneProduct ensembl:ENSG00000138685 fibroblast growth factor 2
GRIN1 GeneProduct ensembl:ENSG00000176884 related to FASD (fetal alcohole spectrum disorder)
NMDA receptor subunit: There are 8 different variants of NR1, produced by alternative splicing of GRIN1
FGF3 GeneProduct ensembl:ENSG00000186895 fibroblast growth factor 3
FGF4 GeneProduct ensembl:ENSG00000075388
FGF5 GeneProduct ensembl:ENSG00000138675
NF1 GeneProduct ensembl:ENSG00000196712 neurofibromatosis 1
DLX5 GeneProduct ensembl:ENSG00000105880 distal-less homeobox 5
controls GABA production
GRIA1 GeneProduct ensembl:ENSG00000155511 effect of MECP2 via LEDGF/PSIP1 influenced change of splice variants proven for mice
Subpart of AMPAR receptor
GRIA3 GeneProduct ensembl:ENSG00000125675 effect of MECP2 via LEDGF/PSIP1 influenced change of splice variants proven for mice
Subpart of AMPAR receptor
GRIA4 GeneProduct ensembl:ENSG00000152578 effect of MECP2 via LEDGF/PSIP1 influenced change of splice variants proven for mice
Subpart of AMPAR receptor


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