MECP2 and Associated Rett Syndrome (Homo sapiens)

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trimethyl lysine 27 neuronal activity leads to increase of Ca2+ effects on specific cells regulation by miRNA (mostly posttranscriptional repression) Oligodendrocytes Activation of transcription (stop of inhibition, res. from phosphorylated MECP2) List of genes and metabolites which are up or downregulated in Rett syndrome MECP2 influences protein synthesis via AKT/mTOR pathway regulation of miRNA cofactors transcriptional and translational regulation of MECP2 Microglia alternative splicing DNA binding upregulated by MECP2 Histone deacetylation MECP2 - HDAC complex Trans-regulator Elements stimulate/inhibit by Polyadenylation of Mecp2 regulation of long noncoding RNA Astrocytes macropinocytosis DNA condensing Promotor elements Cis-Regulatory Elements cell proliferation MYT1 DLX5 GABA BDNF MECP2 DLX6 HP1 hsa-miR-130b-3p Norepinephrine UBE3A NMDA Glutamate SGK1 Serotonin FKBP5 RPS6 EZH2 H3 MPP1 ARHGEF26 IGF2 Dopamine GAD1 HNRNPH1 GRID1 CAMK2A Melatonin GABRR2 AMPA HNRNPF Myoinositol Cytosine methylation APOC2 NREP CSRP1 CDON PRPF3 YB1 MECP2 Ak087060 Ak081227 hsa-miR-184 hsa-miR-29b-1-5p hsa-miR-193a-5p hsa-miR-137 hsa-miR-329-5p hsa-miR-199b-5p hsa-miR-296-5p hsa-miR-382-3p hsa-miR-221-5p hsa-miR-187-5p hsa-miR-92a-3p NCOR1 HB1 SMC3 SST GAMT OPRK1 GPRIN1 Dopamine Norepinephrine Serotonin BRN3 MYT1 SP1 MEF2C RBFOX1 HDAC1 SIN3A MECP2 CNP MBP MAG FGF4 NF1 FUT8 FGF3 GRIN1 DLX5 FGF5 FGF2 hsa-miR-199a-3p hsa-miR-483-5p hsa-miR-132-5p hsa-miR-30a-3p hsa-miR-152-3p TET3 TET2 TET1 TAP1 SP1 TAF1 C/EBP CTCF SP3 E2F1 hsa-miR-222-3p hsa-miR-199a-5p hsa-miR-130a hsa-miR-146b-3p hsa-miR-197-3p hsa-miR-342-3p hsa-miR-409-3p hsa-miR-146a-5p hsa-miR-221-3p hsa-miR-122-5p MTOR PI3K/MAPK AKT1 BRN2 BCL6 REST MECP2 Glutamate GABA CREB1 MECP2 P P RPS6 P BDNF GAMT down regulated by MECP2 Glutamate upregulated by MECP2 down regulated by MECP2 GABA Name: MECP2 and Associated Rett Syndrome Organism: Homo sapiens


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. Please cite this pathways as: Ehrhart et al. 2016

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96364view 23:52, 9 March 2018EgonwConverted interactions to regular arrows, which were not mim:conversions.
96113view 05:10, 18 February 2018EgonwFixed newsline issues.
91190view 22:20, 17 January 2017Khanspersupdated xref for mir-130a
91168view 14:09, 14 January 2017AlexanderPicoQuick edit to datanode annotation or property
91157view 00:23, 13 January 2017FehrhartQuick edit to datanode annotation or property
91156view 00:21, 13 January 2017FehrhartQuick edit to datanode annotation or property
91155view 15:41, 12 January 2017Khanspersupdated xref for PI3K/MAPK pathway
90609view 06:50, 1 December 2016FehrhartModified description
88836view 06:21, 15 August 2016Fehrhartconnected unconnected lines
88439view 01:53, 8 August 2016Mkutmonfix publication reference
88226view 06:03, 1 August 2016FehrhartCorrected citation (wrong pubmed ID)of GAMT and BDNF
87880view 05:16, 25 July 2016RyanmillerOntology Term : 'disease pathway' added !
86084view 07:09, 29 June 2016Fehrhartadded stimulation of MECP2 phosphorylation by neurotransmitters
86083view 06:58, 29 June 2016Fehrhartadded transcription activation pathway
86068view 16:38, 28 June 2016KhanspersOntology Term : 'Rett syndrome' added !
85537view 02:30, 27 May 2016Fehrhartcorrection of typo
85536view 02:28, 27 May 2016FehrhartAdded list of up and downregulated genes and metabolites
85535view 02:15, 27 May 2016FehrhartUpdate epigenetic regulation of MECP2
85534view 01:01, 27 May 2016FehrhartUpdate of gene names
84776view 07:48, 18 March 2016FehrhartModified description
84025view 11:50, 11 January 2016Khanspersremoved comment for hsa-miR-137, which caused character encoding issues
83577view 00:08, 26 November 2015EgonwReplaced the PubMed Central ID with a PubMed ID.
83563view 02:33, 25 November 2015FehrhartFinished miRNA and transregulator elements - pathway is now ready to work with
83541view 08:37, 23 November 2015FehrhartModified description
83540view 07:00, 23 November 2015Fehrharttransfer from M.musculus pathway complete except miRNA and long non-coding RNA
83539view 06:19, 23 November 2015FehrhartNew pathway

External references


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NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AMPAGeneProductENSG00000155511 (Ensembl)Glutamate receptor
APOC2GeneProductENSG00000234906 (Ensembl)apolipoprotein C-II
ARHGEF26GeneProductENSG00000114790 (Ensembl)Rho guanine nucleotide exchange factor (GEF) 26
BCL6GeneProductENSG00000113916 (Ensembl)B cell leukemia/lymphoma 6
BDNFGeneProductENSG00000176697 (Ensembl)brain derived neurotrophic factor
BRN2GeneProductENSG00000184486 (Ensembl)POU domain, class 3, transcription factor 2
BRN3GeneProductENSG00000152192 (Ensembl)POU domain, class 4, transcription factor 1
C/EBPGeneProductENSG00000221869 (Ensembl)CCAAT/enhancer binding protein (Cebpd), delta
CAMK2AGeneProductENSG00000070808 (Ensembl)
CDONGeneProductENSG00000064309 (Ensembl)cell adhesion molecule-related/down-regulated by oncogenes
CNPGeneProductENSG00000173786 (Ensembl)2',3'-cyclic nucleotide 3' phosphodiesterase
CREB1GeneProductENSG00000118260 (Ensembl)
CSRP1GeneProductENSG00000159176 (Ensembl)cysteine and glycine-rich protein 1
CTCFGeneProductENSG00000102974 (Ensembl)CCCTC-binding factor
Cytosine methylation PathwayWP3585 (WikiPathways)
DLX5GeneProductENSG00000105880 (Ensembl)
  • distal-less homeobox 5
  • controls GABA production
DLX6GeneProductENSG00000006377 (Ensembl)
DopamineMetaboliteHMDB00073 (HMDB)
E2F1GeneProductENSG00000101412 (Ensembl)E2F transcription factor 1
EZH2GeneProductENSG00000106462 (Ensembl)histone H3 lysine 27 methyltransferase
FGF2GeneProductENSG00000138685 (Ensembl)fibroblast growth factor 2
FGF3GeneProductENSG00000186895 (Ensembl)fibroblast growth factor 3
FGF4GeneProductENSG00000075388 (Ensembl)
FGF5GeneProductENSG00000138675 (Ensembl)
FKBP5GeneProductENSG00000096060 (Ensembl)
FUT8GeneProductENSG00000033170 (Ensembl)fucosyltransferase 8
GABAMetabolite16865 (ChEBI)
GABRR2GeneProductENSG00000111886 (Ensembl)gamma-aminobutyric acid (GABA) C receptor, subunit rho 2
GAD1GeneProductENSG00000128683 (Ensembl)
GAMTGeneProductENSG00000130005 (Ensembl)guanidinoacetate methyltransferase
GPRIN1GeneProductENSG00000169258 (Ensembl)G protein-regulated inducer of neurite outgrowth 1
GRID1GeneProductENSG00000182771 (Ensembl)
GRIN1GeneProductENSG00000176884 (Ensembl)
  • related to FASD (fetal alcohole spectrum disorder)
  • NMDA receptor subunit: There are 8 different variants of NR1, produced by alternative splicing of GRIN1
GlutamateMetabolite29987 (ChEBI)
H3GeneProductHistone 3
HB1GeneProductchromatin factor, data obtained using human cell line and mouse primary tissue
HDAC1GeneProductENSG00000116478 (Ensembl)
HNRNPFGeneProductENSG00000169813 (Ensembl)
  • Hnrnpf
  • heterogeneous nuclear ribonucleoprotein F
HNRNPH1GeneProductENSG00000169045 (Ensembl)HNRNPH1
IGF2GeneProductENSG00000167244 (Ensembl)
MAGGeneProductENSG00000105695 (Ensembl)myelin-associated glycoprotein
MBPGeneProductENSG00000197971 (Ensembl)myelin basic protein
MECP2GeneProductENSG00000169057 (Ensembl)methyl CpG binding protein 2
MEF2CGeneProductENSG00000081189 (Ensembl)myocyte enhancer factor 2C
MPP1GeneProductENSG00000130830 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYT1GeneProductENSG00000196132 (Ensembl)Myelin transcription factor 1
MelatoninMetaboliteHMDB01389 (HMDB)
MyoinositolMetaboliteHMDB00211 (HMDB)
NCOR1GeneProductENSG00000141027 (Ensembl)nuclear receptor co-repressor 1
NF1GeneProductENSG00000196712 (Ensembl)neurofibromatosis 1
NMDAMetaboliteHMDB02393 (HMDB)N-Methyl-D-aspartic acid
NREPGeneProductENSG00000134986 (Ensembl)neuronal regeneration related protein
NorepinephrineMetaboliteHMDB00216 (HMDB)
OPRK1GeneProductENSG00000082556 (Ensembl)opioid receptor, kappa 1
PI3K/MAPK PathwayWP382 (WikiPathways)
PRPF3GeneProductENSG00000134748 (Ensembl)PRP3 pre-mRNA processing factor 3 homolog (yeast)
RBFOX1GeneProductENSG00000078328 (Ensembl)ataxin 2 binding protein 1, Rbfox1
RESTGeneProductENSG00000084093 (Ensembl)
  • RE1-silencing transcription factor
  • Silences Mecp2 in non-neuronal tissue
RPS6GeneProductENSG00000137154 (Ensembl)
SGK1GeneProductENSG00000118515 (Ensembl)
SIN3AGeneProductENSG00000169375 (Ensembl)
SMC3GeneProductENSG00000108055 (Ensembl)tructural maintenance of chromosomes 3
SP1GeneProductENSG00000185591 (Ensembl)trans-acting transcription factor 1
SP3GeneProductENSG00000172845 (Ensembl)trans-acting transcription factor 3
SSTGeneProductENSG00000157005 (Ensembl)Somatostatin
SerotoninMetaboliteHMDB00259 (HMDB)
TAF1GeneProductENSG00000147133 (Ensembl)TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor
TAP1GeneProductENSG00000168394 (Ensembl)transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
TET1GeneProductENSG00000138336 (Ensembl)tet methylcytosine dioxygenase 1
TET2GeneProductENSG00000168769 (Ensembl)
TET3GeneProductENSG00000187605 (Ensembl)
UBE3AGeneProductENSG00000114062 (Ensembl)
YB1GeneProductENSG00000065978 (Ensembl)
  • data obtained with human cell line and mouse primary tissue
  • Y box protein 1
hsa-miR-122-5pRnaMIMAT0000421 (miRBase mature sequence)
hsa-miR-130aRnaMIMAT0000425 (miRBase mature sequence)Base sequence! It is unclear which mature miRNA was tested.
hsa-miR-130b-3pRnaMIMAT0000691 (miRBase mature sequence)
  • reported for human only
  • binding site at 3'UTR of Mecp2 reported, regulative effect unclear
hsa-miR-132-5pRnaMIMAT0004594 (miRBase mature sequence)
hsa-miR-137RnaMIMAT0000429 (miRBase mature sequence)influences neuronal stem cell proliferation and differentiation
hsa-miR-146a-5p RnaMIMAT0000449 (miRBase mature sequence)
hsa-miR-146b-3p RnaMIMAT0004766 (miRBase mature sequence)
hsa-miR-152-3p RnaMIMAT0000438 (miRBase mature sequence)
hsa-miR-184 RnaMIMAT0000454 (miRBase mature sequence)The effect of Mecp2 on miR-184 is discussed controversially: Nomura et al. 2008 reports an Mecp2 dependant repression of miR-184 while Liu et al. 2010 reports no effect of Mecp2 but an MBD1 dependant regulation of miR-184
hsa-miR-187-5p RnaMIMAT0004561 (miRBase mature sequence)no connection between Mecp2 and miR-187 in other sources than [3]
hsa-miR-193a-5p RnaMIMAT0004614 (miRBase mature sequence)
hsa-miR-197-3p RnaMIMAT0000227 (miRBase mature sequence)
hsa-miR-199a-3pRnaMIMAT0000232 (miRBase mature sequence)
hsa-miR-199a-5pRnaMIMAT0000231 (miRBase mature sequence)
hsa-miR-199b-5p RnaMIMAT0000263 (miRBase mature sequence)
hsa-miR-221-3pRnaMIMAT0000278 (miRBase mature sequence)
hsa-miR-221-5pRnaMIMAT0004568 (miRBase mature sequence)
hsa-miR-222-3pRnaMIMAT0000279 (miRBase mature sequence)
hsa-miR-296-5pRnaMIMAT0000690 (miRBase mature sequence)
hsa-miR-29b-1-5p RnaMIMAT0004514 (miRBase mature sequence)
hsa-miR-30a-3p RnaMIMAT0000088 (miRBase mature sequence)reported for human umbilical vein endothelial cells only
hsa-miR-329-5pRnaMIMAT0026555 (miRBase mature sequence)
hsa-miR-342-3pRnaMIMAT0000753 (miRBase mature sequence)
hsa-miR-382-3pRnaMIMAT0022697 (miRBase mature sequence)
hsa-miR-409-3pRnaMIMAT0001639 (miRBase mature sequence)
hsa-miR-483-5pRnaMIMAT0004761 (miRBase mature sequence)inhibition of Mecp2 expression only reported for human!
hsa-miR-92a-3p RnaMIMAT0000092 (miRBase mature sequence)

Annotated Interactions

<cite>No annotated interactions</cite>