MECP2 and Associated Rett Syndrome (Homo sapiens)

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23114, 2832, 3326135131313131313DNA bindingCis-Regulatory Elementsregulation oflong noncoding RNAneuronal activityleads to increase of Ca2+ Astrocytesmacropinocytosis List of genes and metabolites which are up or downregulated in Rett syndrome cell proliferationregulation by miRNA (mostlyposttranscriptional repression)Histone deacetylationtranscriptional and translationalregulation of MECP2trimethyl lysine 27regulation ofmiRNAActivation of transcription(stop of inhibition, res. fromphosphorylated MECP2)MECP2 influencesprotein synthesis viaAKT/mTOR pathwayOligodendrocytesDNA condensingPromotor elementseffects on specific cellsMicrogliaalternativesplicing upregulatedby MECP2cofactorsMECP2 - HDAC complex Trans-regulator Elements stimulate/inhibitby Polyadenylation of Mecp2 22hsa-miR-382-3pAMPAhsa-miR-132-5phsa-miR-193a-5p HB1hsa-miR-187-5p hsa-miR-146b-3p GPRIN1hsa-miR-137GAD1hsa-miR-221-3pDLX5C/EBPIGF1RRESTSMC3MYT1RBFOX1CNPTET1CAMK2AGRID1hsa-miR-199a-3pHP1MelatoninCytosine methylation DLX6hsa-miR-122-5phsa-miR-30a-3p MECP2SP3MPP1MyoinositolNREPhsa-miR-199a-5pTrofinetideMYT1PRPF3hsa-miR-222-3pMAGhsa-miR-342-3pUBE3AHNRNPH1hsa-miR-130b-3pMEF2CTAP1APOC2E2F1GABRR2HDAC1hsa-miR-296-5pOPRK1hsa-miR-152-3p hsa-miR-130aMBPEZH2hsa-miR-29b-1-5p hsa-miR-409-3pGlycinehsa-miR-92a-3p NorepinephrineSerotoninBRN3CSRP1hsa-miR-483-5phsa-miR-146a-5p FKBP5hsa-miR-184 NCOR1Ak081227hsa-miR-329-5phsa-miR-197-3p CDONH3Ak087060GABATET2BDNFPI3K/MAPK RPS6hsa-miR-199b-5p DopamineIGF2GAMTBRN2SIN3Ahsa-miR-221-5pSSTSP1HNRNPFMTORNMDAARHGEF26SGK1SerotoninTAF1BCL6NorepinephrineDopamineTET3CTCFGlutamateAKT1201710201721722020222016120173212024227148202017161623429, 24929, 191515292717821123615235253020223120115231827202220YB114, 28MECP2MECP2SP1Glutamate16, 23GABA30CREB1PPRPS6PBDNF2GAMTdown regulatedby MECP217Glutamate30upregulatedby MECP2down regulatedby MECP2GABAMECP2D-serineIGF1FOXG1PI3KPTENDHX9FUSHNRNPFTARDBPPSIP1262626FUT82FGF2GRIN12FGF328FGF42FGF522NF112DLX5GRIA19, 2826GRIA326GRIA426


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

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110253view13:46, 30 April 2020Fehrhartadded information on Trofinetide
108350view09:14, 11 December 2019L DupuisConnected line
107144view14:22, 17 September 2019MaintBotChEBI identifier normalization
106741view13:22, 17 September 2019MaintBotHMDB identifier normalization
106637view21:00, 12 September 2019KhanspersModified description
105641view05:07, 10 August 2019KhanspersModified description
104944view12:54, 26 June 2019Fehrhartfixed line connections
104930view13:52, 25 June 2019FehrhartModified description
104929view13:49, 25 June 2019FehrhartModified description
104928view13:49, 25 June 2019FehrhartReverted to version '13:06, 25 June 2019' by Fehrhart
104927view13:44, 25 June 2019FehrhartModified description
104926view13:06, 25 June 2019FehrhartUpdate with recent literature concerning alternative splicing, IGF1 pathway and GRIN1 agonists
97933view11:43, 25 June 2018FehrhartModified description
96364view06:52, 10 March 2018EgonwConverted interactions to regular arrows, which were not mim:conversions.
96113view12:10, 18 February 2018EgonwFixed newsline issues.
91190view05:20, 18 January 2017Khanspersupdated xref for mir-130a
91168view21:09, 14 January 2017AlexanderPicoQuick edit to datanode annotation or property
91157view07:23, 13 January 2017FehrhartQuick edit to datanode annotation or property
91156view07:21, 13 January 2017FehrhartQuick edit to datanode annotation or property
91155view22:41, 12 January 2017Khanspersupdated xref for PI3K/MAPK pathway
90609view13:50, 1 December 2016FehrhartModified description
88836view13:21, 15 August 2016Fehrhartconnected unconnected lines
88439view08:53, 8 August 2016Mkutmonfix publication reference
88226view13:03, 1 August 2016FehrhartCorrected citation (wrong pubmed ID)of GAMT and BDNF
87880view12:16, 25 July 2016RyanmillerOntology Term : 'disease pathway' added !
86084view14:09, 29 June 2016Fehrhartadded stimulation of MECP2 phosphorylation by neurotransmitters
86083view13:58, 29 June 2016Fehrhartadded transcription activation pathway
86068view23:38, 28 June 2016KhanspersOntology Term : 'Rett syndrome' added !
85537view09:30, 27 May 2016Fehrhartcorrection of typo
85536view09:28, 27 May 2016FehrhartAdded list of up and downregulated genes and metabolites
85535view09:15, 27 May 2016FehrhartUpdate epigenetic regulation of MECP2
85534view08:01, 27 May 2016FehrhartUpdate of gene names
84776view14:48, 18 March 2016FehrhartModified description
84025view18:50, 11 January 2016Khanspersremoved comment for hsa-miR-137, which caused character encoding issues
83577view07:08, 26 November 2015EgonwReplaced the PubMed Central ID with a PubMed ID.
83563view09:33, 25 November 2015FehrhartFinished miRNA and transregulator elements - pathway is now ready to work with
83541view15:37, 23 November 2015FehrhartModified description
83540view14:00, 23 November 2015Fehrharttransfer from M.musculus pathway complete except miRNA and long non-coding RNA
83539view13:19, 23 November 2015FehrhartNew pathway

External references


View all...
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)
D-serineMetaboliteCHEBI:16523 (ChEBI)
DHX9GeneProductENSG00000135829 (Ensembl) binding to MECP2 confirmed in mice
DLX5GeneProductENSG00000105880 (Ensembl)
  • distal-less homeobox 5
  • controls GABA production
DLX6GeneProductENSG00000006377 (Ensembl)
DopamineMetaboliteHMDB0000073 (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)
FOXG1GeneProductENSG00000176165 (Ensembl) Glutamate receptor
FUSGeneProductENSG00000089280 (Ensembl) binding to MECP2 confirmed in mice
FUT8GeneProductENSG00000033170 (Ensembl) fucosyltransferase 8
GABAMetaboliteCHEBI:16865 (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
GRIA1GeneProductENSG00000155511 (Ensembl)
  • effect of MECP2 via LEDGF/PSIP1 influenced change of splice variants proven for mice
  • Subpart of AMPAR receptor
GRIA3GeneProductENSG00000125675 (Ensembl)
  • effect of MECP2 via LEDGF/PSIP1 influenced change of splice variants proven for mice
  • Subpart of AMPAR receptor
GRIA4GeneProductENSG00000152578 (Ensembl)
  • effect of MECP2 via LEDGF/PSIP1 influenced change of splice variants proven for mice
  • Subpart of AMPAR receptor
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
GlutamateMetaboliteCHEBI:29987 (ChEBI)
GlycineMetaboliteHMDB0000123 (HMDB)
H3GeneProductHistone 3
HB1GeneProductchromatin factor, data obtained using human cell line and mouse primary tissue
HDAC1GeneProductENSG00000116478 (Ensembl)
HNRNPFGeneProductENSG00000169813 (Ensembl)
  • binding to MECP2 confirmed in mice
  • also known as hnRNPH+F
HNRNPH1GeneProductENSG00000169045 (Ensembl) HNRNPH1
IGF1GeneProductENSG00000017427 (Ensembl) Glutamate receptor
IGF1RGeneProductENSG00000140443 (Ensembl)
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
MelatoninMetaboliteHMDB0001389 (HMDB)
MyoinositolMetaboliteHMDB0000211 (HMDB)
NCOR1GeneProductENSG00000141027 (Ensembl) nuclear receptor co-repressor 1
NF1GeneProductENSG00000196712 (Ensembl) neurofibromatosis 1
NMDAMetaboliteHMDB0002393 (HMDB) N-Methyl-D-aspartic acid
NREPGeneProductENSG00000134986 (Ensembl) neuronal regeneration related protein
NorepinephrineMetaboliteHMDB0000216 (HMDB)
OPRK1GeneProductENSG00000082556 (Ensembl) opioid receptor, kappa 1
PI3K/MAPK PathwayWP382 (WikiPathways)
PRPF3GeneProductENSG00000134748 (Ensembl) PRP3 pre-mRNA processing factor 3 homolog (yeast)
PSIP1GeneProductENSG00000164985 (Ensembl)
  • binding to MECP2 confirmed in mice
  • also known as LEDGF
PTENGeneProductENSG00000171862 (Ensembl)
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
SerotoninMetaboliteHMDB0000259 (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)
TARDBPGeneProductENSG00000120948 (Ensembl)
  • binding to MECP2 confirmed in mice
  • also known as TDP-43
TET1GeneProductENSG00000138336 (Ensembl) tet methylcytosine dioxygenase 1
TET2GeneProductENSG00000168769 (Ensembl)
TET3GeneProductENSG00000187605 (Ensembl)
TrofinetideMetabolite11318905 (PubChem-compound)
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

No annotated interactions

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