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MEG3 (maternally expressed 3)

Written2008-11Yunli Zhou
Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

(Note : for Links provided by Atlas : click)


Other namesFP504
HGNC (Hugo) MEG3
LocusID (NCBI) 55384
Atlas_Id 44393
Location 14q32.2
Location_base_pair Starts at 101292445 and ends at 101327360 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Genes flanking MEG3, in centromere to telomere direction on 14q32.2, are:
- DLK1 14q32.2 Delta-like 1 homolog (Drosophila)
- MEG3 14q32.2 Maternally Expressed Gene 3
- RTL1 14q32.31 Retrotransposon-like 1


Note The MEG3 gene is a maternally expressed imprinted gene. It forms the MEG3/DLK1 imprinted locus on 14q32, which contains multiple paternally or maternally imprinted genes, microRNAs and small nucleolar RNAs.
Description The MEG3 gene spans a region of 34,906 bp and consists of 10 exons.
Transcription Multiple transcripts are generated from the MEG3 gene due to alternative RNA splicing. The most prominent MEG3 transcript form is approximately 1.6 k nucleotides long and consists of exons 1, 2, 3, 4, 8, 9 and 10. This transcript is also known as the MEG3 transcript variant 1 (GenBank NR_002766).


Note MEG3 transcripts are non-coding RNAs (ncRNAs), which do not encode any functional proteins.
Expression MEG3 ncRNAs are highly expressed in brain, pituitary, placenta and adrenal gland; moderately in pancreas, ovary and testis; low in liver, prostate, spleen and mammary gland.
Function MEG3 does not encode any functional proteins. It acts as an RNA. The folding of MEG3 RNA plays an important role in its function. MEG3 ncRNAs have been shown to inhibit proliferation of several human tumor cell lines in culture. Transient expression of MEG3 activates p53 and induces the p53-dependent expression of its target gene GDF15. However, MEG3 can inhibit cell proliferation in the absence of p53.

Implicated in

Entity Clinically non-functioning pituitary adenomas
Disease Human pituitary adenomas arise from the anterior lobe of the pituitary, which contains hormone-secreting cells including somatotrophs (producing growth hormone), lactotrophs (prolactin), corticotrophs (adrenocorticotropic hormone), thyrotrophs (thyroid stimulating hormone) and gonadotrophs (follicle-stimulating hormone and luteinizing hormone). Clinically non-functioning pituitary adenomas usually show evidence of production of intact glycoprotein hormones and their free alpha and beta subunits yet typically do not secrete excessive hormones associated with a clinical syndrome. They are mostly derived from gonadotrophs. These tumors may grow large and cause considerable morbidity due to compression of adjacent normal structures.
Oncogenesis Expression of the MEG3 gene is lost in virtually all clinically non-functioning tumors of gonadotroph origin, but readily detectable in hormone-secreting clinically functioning tumors. The lack of MEG3 expression is most likely due to hypermethylation in the MEG3 gene promoter and in a region, called IG-DMR, which regulates imprinting of the MEG3 gene.
Entity Other human cancers
Oncogenesis MEG3 expression is lost in many human cancer cell lines. They include breast cancer lines MCF7 and T47D; bladder cancer lines T24 and 5637; prostate cancer line Du145; lung cancer line H1299; colon cancer lines HT29 and HT116; brain cancer lines H4, Kelly, SK-N-AS, SK-N-DZ and SK-N-F1. MEG3 expression is affected in 25% of primary neuroblastoma tumors.


The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA.
Schuster-Gossler K, Bilinski P, Sado T, Ferguson-Smith A, Gossler A.
Dev Dyn. 1998 Jun;212(2):214-28.
PMID 9626496
Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q.
Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F.
Genes Cells. 2000 Mar;5(3):211-20.
PMID 10759892
Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12.
Lin SP, Youngson N, Takada S, Seitz H, Reik W, Paulsen M, Cavaille J, Ferguson-Smith AC.
Nat Genet. 2003 Sep;35(1):97-102.
PMID 12937418
A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.
Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A.
J Clin Endocrinol Metab. 2003 Nov;88(11):5119-26.
PMID 14602737
Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour.
Astuti D, Latif F, Wagner K, Gentle D, Cooper WN, Catchpoole D, Grundy R, Ferguson-Smith AC, Maher ER.
Br J Cancer. 2005 Apr 25;92(8):1574-80.
PMID 15798773
Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors.
Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A.
J Clin Endocrinol Metab. 2005 Apr;90(4):2179-86.
PMID 15644399
High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12.
Tierling S, Dalbert S, Schoppenhorst S, Tsai CE, Oliger S, Ferguson-Smith AC, Paulsen M, Walter J.
Genomics. 2006 Feb;87(2):225-35.
PMID 16309881
Activation of p53 by MEG3 non-coding RNA.
Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A.
J Biol Chem. 2007 Aug 24;282(34):24731-42.
PMID 17569660
Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas.
Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A.
J Clin Endocrinol Metab. 2008 Oct;93(10):4119-25.
PMID 18628527


This paper should be referenced as such :
Zhou, Y
MEG3 (maternally expressed 3)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(10):726-727.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)MEG3   14575
Entrez_Gene (NCBI)MEG3  55384  maternally expressed 3 (non-protein coding)
GeneCards (Weizmann)MEG3
Ensembl hg19 (Hinxton)ENSG00000214548 [Gene_View]  chr14:101292445-101327360 [Contig_View]  MEG3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000214548 [Gene_View]  chr14:101292445-101327360 [Contig_View]  MEG3 [Vega]
ICGC DataPortalENSG00000214548
TCGA cBioPortalMEG3
AceView (NCBI)MEG3
Genatlas (Paris)MEG3
SOURCE (Princeton)MEG3
Genomic and cartography
GoldenPath hg19 (UCSC)MEG3  -     chr14:101292445-101327360 +  14q32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MEG3  -     14q32   [Description]    (hg38-Dec_2013)
EnsemblMEG3 - 14q32 [CytoView hg19]  MEG3 - 14q32 [CytoView hg38]
Mapping of homologs : NCBIMEG3 [Mapview hg19]  MEG3 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB032607 AF052114 AJ413186 AJ413187 AK055725
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)NC_000014 NC_018925 NG_016853 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)MEG3
Cluster EST : UnigeneHs.654863 [ NCBI ]
CGAP (NCI)Hs.654863
Alternative Splicing : Fast-db (Paris)GSHG0045814
Alternative Splicing GalleryENSG00000214548
Gene ExpressionMEG3 [ NCBI-GEO ]     MEG3 [ SEEK ]   MEG3 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UI56 (Uniprot)
NextProtQ9UI56  [Medical]  [Publications]
With graphics : InterProQ9UI56
Splice isoforms : SwissVarQ9UI56 (Swissvar)
Related proteins : CluSTrQ9UI56
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
DMDM Disease mutations55384
Blocks (Seattle)Q9UI56
Human Protein AtlasENSG00000214548
Peptide AtlasQ9UI56
IPIIPI00006049   IPI00384148   
Protein Interaction databases
IntAct (EBI)Q9UI56
Ontologies - Pathways
Ontology : AmiGO
Ontology : EGO-EBI
Protein Interaction DatabaseMEG3
Atlas of Cancer Signalling NetworkMEG3
Wikipedia pathwaysMEG3
Gene fusions - Rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerMEG3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MEG3
Exome Variant ServerMEG3
SNP (GeneSNP Utah)MEG3
Genetic variants : HAPMAPMEG3
Genomic Variants (DGV)MEG3 [DGVbeta]
ICGC Data PortalMEG3 
TCGA Data PortalMEG3 
Tumor PortalMEG3
TCGA Copy Number PortalMEG3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DoCM (Curated mutations)MEG3
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
DECIPHER (Syndromes)14:101292445-101327360
CONAN: Copy Number AnalysisMEG3 
Mutations and Diseases : HGMDMEG3
NextProtQ9UI56 [Medical]
Huge Navigator MEG3 [HugePedia]  MEG3 [HugeCancerGEM]
snp3D : Map Gene to Disease55384
DGIdb (Drug Gene Interaction db)MEG3
BioCentury BCIQMEG3
General knowledge
Homologs : HomoloGeneMEG3
Homology/Alignments : Family Browser (UCSC)MEG3
Phylogenetic Trees/Animal Genes : TreeFamMEG3
Chemical/Protein Interactions : CTD55384
Chemical/Pharm GKB GenePA30737
Clinical trialMEG3
Cancer Resource (Charite)ENSG00000214548
Other databases
PubMed44 Pubmed reference(s) in Entrez
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Nov 28 14:36:00 CET 2015

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