Mecp2 and associated Rett syndrome (WP2910)

Mus musculus

Mecp2 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. The pathway is demonstrated for mouse but as the genes are highly conserved in mammals, many of these are valid for human, too.


Friederike Ehrhart , Egon Willighagen , Alex Pico , Kristina Hanspers , Elisa Cirillo , Lotte Sevenich , Martina Summer-Kutmon , and Eric Weitz


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Mus musculus




Pathway Ontology

regulatory pathway disease pathway regulatory pathway pertinent to the brain


Label Type Compact URI Comment
GABA Metabolite chebi:16865
Glutamate Metabolite chebi:29987
Ncor1 GeneProduct ensembl:ENSMUSG00000018501 nuclear receptor co-repressor 1
MYT1 GeneProduct ensembl:ENSMUSG00000010505 myelin transcription factor 1
proof of Mecp2 inhibition in Oligodendrocytes
Brn3 GeneProduct ensembl:ENSMUSG00000048349 POU domain, class 4, transcription factor 1
Apoc2 GeneProduct ensembl:ENSMUSG00000002992 apolipoprotein C-II
Fgf4 GeneProduct ensembl:ENSMUSG00000050917
Bdnf GeneProduct ensembl:ENSMUSG00000048482 brain derived neurotrophic factor
Nf1 GeneProduct ensembl:ENSMUSG00000020716 neurofibromatosis 1
Sst GeneProduct ensembl:ENSMUSG00000004366 Somatostatin
Nrep GeneProduct ensembl:ENSMUSG00000042834 neuronal regeneration related protein
Fut8 GeneProduct ensembl:ENSMUSG00000021065 fucosyltransferase 8
Mecp2 GeneProduct ensembl:ENSMUSG00000031393 methyl CpG binding protein 2
Brn2 GeneProduct ensembl:ENSMUSG00000095139 POU domain, class 3, transcription factor 2
YB1 GeneProduct ensembl:ENSMUSG00000028639 data obtained with human cell line and mouse primary tissue
Fgf3 GeneProduct ensembl:ENSMUSG00000031074 fibroblast growth factor 3
Smc3 GeneProduct ensembl:ENSMUSG00000024974 tructural maintenance of chromosomes 3
NR1/GRIN1 GeneProduct ensembl:ENSMUSG00000026959 related to FASD (fetal alcohole spectrum disorder)
NMDA receptor subunit: There are 8 different variants of NR1, produced by alternative splicing of GRIN1
Mef2c GeneProduct ensembl:ENSMUSG00000005583 myocyte enhancer factor 2C
TAP1 GeneProduct ensembl:ENSMUSG00000037321 transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
A2bp1 GeneProduct ensembl:ENSMUSG00000008658 ataxin 2 binding protein 1
CNPase GeneProduct ensembl:ENSMUSG00000006782 2',3'-cyclic nucleotide 3' phosphodiesterase
Ezh2 GeneProduct ensembl:ENSMUSG00000029687 histone H3 lysine 27 methyltransferase
Gamt GeneProduct ensembl:ENSMUSG00000020150 guanidinoacetate methyltransferase
Oprk1 GeneProduct ensembl:ENSMUSG00000025905 opioid receptor, kappa 1
Arhgef26 GeneProduct ensembl:ENSMUSG00000036885 Rho guanine nucleotide exchange factor (GEF) 26
Sin3a GeneProduct ensembl:ENSMUSG00000042557
SP1 GeneProduct ensembl:ENSMUSG00000001280 trans-acting transcription factor 1
GAD1 GeneProduct ensembl:ENSMUSG00000070880
TAF1 GeneProduct ensembl:ENSMUSG00000031314 TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor
hnRNP H GeneProduct ensembl:ENSMUSG00000007850 HNRNPH1
Csrp1 GeneProduct ensembl:ENSMUSG00000026421 cysteine and glycine-rich protein 1
Dlx5 GeneProduct ensembl:ENSMUSG00000029755 distal-less homeobox 5
controls GABA production
Cdon GeneProduct ensembl:ENSMUSG00000038119 cell adhesion molecule-related/down-regulated by oncogenes
MYT1 GeneProduct ensembl:ENSMUSG00000010505 Myelin transcription factor 1
C/EBP GeneProduct ensembl:ENSMUSG00000071637 CCAAT/enhancer binding protein (Cebpd), delta
Mbp GeneProduct ensembl:ENSMUSG00000041607 myelin basic protein
BCL6 GeneProduct ensembl:ENSMUSG00000022508 B cell leukemia/lymphoma 6
Gabrr2 GeneProduct ensembl:ENSMUSG00000023267 gamma-aminobutyric acid (GABA) C receptor, subunit rho 2
CTCF GeneProduct ensembl:ENSMUSG00000005698 CCCTC-binding factor
SP3 GeneProduct ensembl:ENSMUSG00000027109 trans-acting transcription factor 3
PRPF3 GeneProduct ensembl:ENSMUSG00000015748 PRP3 pre-mRNA processing factor 3 homolog (yeast)
E2F1 GeneProduct ensembl:ENSMUSG00000027490 E2F transcription factor 1
REST GeneProduct ensembl:ENSMUSG00000029249 RE1-silencing transcription factor
Silences Mecp2 in non-neuronal tissue
Mag GeneProduct ensembl:ENSMUSG00000036634 myelin-associated glycoprotein
Fgf2 GeneProduct ensembl:ENSMUSG00000037225 fibroblast growth factor 2
Gprin1 GeneProduct ensembl:ENSMUSG00000069227 G protein-regulated inducer of neurite outgrowth 1
Tet1 GeneProduct ensembl:ENSMUSG00000047146 tet methylcytosine dioxygenase 1
hnRNP F GeneProduct ensembl:ENSMUSG00000042079 Hnrnpf
heterogeneous nuclear ribonucleoprotein F
YB1 GeneProduct ensembl:ENSMUSG00000028639 data obtained with human cell line and mouse primary tissue
Y box protein 1
Creb1 GeneProduct ensembl:ENSMUSG00000025958
Mecp2 GeneProduct ensembl:ENSMUSG00000031393 methyl CpG binding protein 2
Mecp2 GeneProduct ensembl:ENSMUSG00000031393 methyl CpG binding protein 2
Mecp2 GeneProduct ensembl:ENSMUSG00000031393 methyl CpG binding protein 2
SP1 GeneProduct ensembl:ENSMUSG00000001280 trans-acting transcription factor 1


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