Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

MSX2 (Msh Homeobox 2)

Written2013-11Kennichi Satoh
Division of Cancer stem cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Shiote, Medeshima, Natori city, Miyagi 981-1293, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)CRS2
FPP
HOX8
MSH
PFM
PFM1
HGNC (Hugo) MSX2
HGNC Alias symbCRS2
FPP
HOX8
MSH
PFM
HGNC Alias namecraniosynostosis, type 2
HGNC Previous namePFM1
HGNC Previous namemsh (Drosophila) homeo box homolog 2
 parietal foramina 1
 msh homeobox homolog 2 (Drosophila)
LocusID (NCBI) 4488
Atlas_Id 41438
Location 5q35.2  [Link to chromosome band 5q35]
Location_base_pair Starts at 174724582 and ends at 174730896 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MSX2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
TOM1L1 (17q22)::MSX2 (5q35.2)

DNA/RNA

Description MSX2 contains two exons. The length of MSX2 gene is 6328 bases.
Transcription 2224 bases mRNA; 801 bases of coding region.
Pseudogene One pseudogene was reported (Hodgkinson et al., 1993).

Protein

Description This gene encodes a member of the muscle segment homeobox gene family that consists of 267 amino acids. The molecular weight of the encoded protein is about 29 kDa. MSX2 is a transcriptional repressor which regulates a balance between survival and apoptosis of neural crest-derived cells for proper craniofacial morphogenesis (Davidson, 1995). MSX2 is also shown to be an important target for the RAS signaling pathways (Takahashi et al., 1996). The expression pattern of this gene in the development of organs suggests its pivotal role in epithelial-mesenchymal interactions (Satoh et al., 2004). On the other hand, accumulating evidence has revealed the active involvement of this gene in tumorigenesis and/or tumor development (Satoh et al., 2012).
Expression The expression of MSX2 is observed in a variety of sites, including premigratory cranial neural crest, tooth, and mammary gland, etc (Takahashi and Le Douarin, 1990; Davidson, 1995; Satoh et al., 2004). In addition, enhanced expression of MSX2 is found in several cancer species (Satoh et al., 2012).
Localisation Located at cell nuclei.
Function MSX2 act as a transcriptional regulator in the development multiple organs such as bone, neural crest and mammary gland, and play a role in limb-pattern and teeth formation (Davidson, 1995). MSX2 may induce the proliferation of osteoprogenitors (Dodig et al., 1999), as well as osteoblasts (Liu et al., 1999), and this gene was also related to the enhancement of branching morphogenesis in mouse mammary ducts (Satoh et al., 2007).
Homology Mus musculus Msx2; Xenopus laevis msx2-A; Drosophila melanogaster Dr.

Mutations

Germinal Mutations in this gene are associated with Boston type craniosynostosis (Jabs et al., 1993).

Implicated in

Note
  
Entity Pancreatic cancer
Note MSX2 is shown to be indispensable for BMP-induced epithelial to mesenchymal transition (EMT) in pancreatic cancer cells (Hamada et al., 2007) . Increased expression of this gene was significantly correlated with higher tumor grade, vascular invasion and Twist 1 expression (Satoh, et al., 2008). In addition, MSX2 has been shown to enhance the chemoresistance through ABCG2 induction and increase in the cancer stem cell phenotype (Hamada et al., 2012; Satoh et al., 2012) (Figure 1).
 
  
  
Entity Gastric cancer
Note MSX2 was identified as a cancer- specific hedgehog target and the down-regulation of this gene resulted in the inhibition of cancer cell growth in vitro (Ohta et al., 2009).
  
  
Entity Ovarian cancer
Note MSX2 has been shown to be a downstream target of WNT signal and has been correlated with the invasiveness of ovarian endometrioid adenocarcinoma (Zhai et al., 2011).
  
  
Entity Breast carcinoma
Note The expression of this gene was associated with good prognosis in breast cancer patients (Lanigan et al., 2010).
  
  
Entity Malignant melanoma
Note The expression of this gene was associated with good prognosis in malignant melanoma patients (Gremel et al., 2011).
  
  
Entity Prostate carcinoma
Note This gene expression was increased significantly in tumors with metastasis compared to those without metastasis in prostate carcinoma (Chua et al., 2010).
  

Bibliography

Differential expression of MSX2 in nodular hyperplasia, high-grade prostatic intraepithelial neoplasia and prostate adenocarcinoma.
Chua CW, Chiu YT, Yuen HF, Chan KW, Wang X, Ling MT, Wong YC.
APMIS. 2010 Dec;118(12):918-26. doi: 10.1111/j.1600-0463.2010.02626.x. Epub 2010 Oct 13.
PMID 21091772
 
The function and evolution of Msx genes: pointers and paradoxes.
Davidson D.
Trends Genet. 1995 Oct;11(10):405-11. (REVIEW)
PMID 7482767
 
Ectopic Msx2 overexpression inhibits and Msx2 antisense stimulates calvarial osteoblast differentiation.
Dodig M, Tadic T, Kronenberg MS, Dacic S, Liu YH, Maxson R, Rowe DW, Lichtler AC.
Dev Biol. 1999 May 15;209(2):298-307.
PMID 10328922
 
Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma.
Gremel G, Ryan D, Rafferty M, Lanigan F, Hegarty S, Lavelle M, Murphy I, Unwin L, Joyce C, Faller W, McDermott EW, Sheahan K, Ponten F, Gallagher WM.
Br J Cancer. 2011 Aug 9;105(4):565-74. doi: 10.1038/bjc.2011.249. Epub 2011 Jul 5.
PMID 21730974
 
The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2.
Hamada S, Satoh K, Hirota M, Kanno A, Umino J, Ito H, Masamune A, Kikuta K, Kume K, Shimosegawa T.
J Cell Physiol. 2012 Feb;227(2):729-38. doi: 10.1002/jcp.22781.
PMID 21465479
 
Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells.
Hodgkinson JE, Davidson CL, Beresford J, Sharpe PT.
Biochim Biophys Acta. 1993 Jul 18;1174(1):11-6.
PMID 8101453
 
A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis.
Jabs EW, Muller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB, et al.
Cell. 1993 Nov 5;75(3):443-50.
PMID 8106171
 
Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro.
Lanigan F, Gremel G, Hughes R, Brennan DJ, Martin F, Jirstrom K, Gallagher WM.
Breast Cancer Res. 2010;12(4):R59. doi: 10.1186/bcr2621. Epub 2010 Aug 3.
PMID 20682066
 
Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans.
Liu YH, Tang Z, Kundu RK, Wu L, Luo W, Zhu D, Sangiorgi F, Snead ML, Maxson RE.
Dev Biol. 1999 Jan 15;205(2):260-74.
PMID 9917362
 
Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers.
Ohta H, Aoyagi K, Fukaya M, Danjoh I, Ohta A, Isohata N, Saeki N, Taniguchi H, Sakamoto H, Shimoda T, Tani T, Yoshida T, Sasaki H.
Br J Cancer. 2009 Jan 27;100(2):389-98. doi: 10.1038/sj.bjc.6604846. Epub 2008 Dec 23.
PMID 19107131
 
Msx-1 and Msx-2 in mammary gland development.
Satoh K, Ginsburg E, Vonderhaar BK.
J Mammary Gland Biol Neoplasia. 2004 Apr;9(2):195-205. (REVIEW)
PMID 15300013
 
MSX2 in pancreatic tumor development and its clinical application for the diagnosis of pancreatic ductal adenocarcinoma.
Satoh K, Hamada S, Shimosegawa T.
Front Physiol. 2012 Nov 14;3:430. doi: 10.3389/fphys.2012.00430. eCollection 2012.
PMID 23162473
 
Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2.
Satoh K, Hovey RC, Malewski T, Warri A, Goldhar AS, Ginsburg E, Saito K, Lydon JP, Vonderhaar BK.
Oncogene. 2007 Nov 29;26(54):7526-34. Epub 2007 Jun 4.
PMID 17546050
 
Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene.
Takahashi C, Akiyama N, Matsuzaki T, Takai S, Kitayama H, Noda M.
Oncogene. 1996 May 16;12(10):2137-46.
PMID 8668339
 
cDNA cloning of a quail homeobox gene and its expression in neural crest-derived mesenchyme and lateral plate mesoderm.
Takahashi Y, Le Douarin N.
Proc Natl Acad Sci U S A. 1990 Oct;87(19):7482-6.
PMID 1977161
 
MSX2 is an oncogenic downstream target of activated WNT signaling in ovarian endometrioid adenocarcinoma.
Zhai Y, Iura A, Yeasmin S, Wiese AB, Wu R, Feng Y, Fearon ER, Cho KR.
Oncogene. 2011 Oct 6;30(40):4152-62. doi: 10.1038/onc.2011.123. Epub 2011 Apr 18.
PMID 21499300
 

Citation

This paper should be referenced as such :
Satoh K
MSX2 (Msh Homeobox 2);
Atlas Genet Cytogenet Oncol Haematol. in press


External links

 

Nomenclature
HGNC (Hugo)MSX2   7392
Cards
AtlasMSX2ID41438ch5q35
Entrez_Gene (NCBI)MSX2    msh homeobox 2
AliasesCRS2; FPP; HOX8; MSH; 
PFM; PFM1
GeneCards (Weizmann)MSX2
Ensembl hg19 (Hinxton)ENSG00000120149 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000120149 [Gene_View]  ENSG00000120149 [Sequence]  chr5:174724582-174730896 [Contig_View]  MSX2 [Vega]
ICGC DataPortalENSG00000120149
TCGA cBioPortalMSX2
AceView (NCBI)MSX2
Genatlas (Paris)MSX2
SOURCE (Princeton)MSX2
Genetics Home Reference (NIH)MSX2
Genomic and cartography
GoldenPath hg38 (UCSC)MSX2  -     chr5:174724582-174730896 +  5q35.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MSX2  -     5q35.2   [Description]    (hg19-Feb_2009)
GoldenPathMSX2 - 5q35.2 [CytoView hg19]  MSX2 - 5q35.2 [CytoView hg38]
ImmunoBaseENSG00000120149
Genome Data Viewer NCBIMSX2 [Mapview hg19]  
OMIM123101   168500   168550   604757   
Gene and transcription
Genbank (Entrez)AL552909 BC015509 BT009814 D14970 D26145
RefSeq transcript (Entrez)NM_001363626 NM_002449
Consensus coding sequences : CCDS (NCBI)MSX2
Gene ExpressionMSX2 [ NCBI-GEO ]   MSX2 [ EBI - ARRAY_EXPRESS ]   MSX2 [ SEEK ]   MSX2 [ MEM ]
Gene Expression Viewer (FireBrowse)MSX2 [ Firebrowse - Broad ]
GenevisibleExpression of MSX2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4488
GTEX Portal (Tissue expression)MSX2
Human Protein AtlasENSG00000120149-MSX2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP35548   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP35548  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP35548
PhosPhoSitePlusP35548
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (EBI)Homeobox-like_sf    Homeobox_CS    Homeobox_dom    Homeobox_metazoa   
Domain families : Pfam (Sanger)Homeodomain (PF00046)   
Domain families : Pfam (NCBI)pfam00046   
Domain families : Smart (EMBL)HOX (SM00389)  
Conserved Domain (NCBI)MSX2
SuperfamilyP35548
AlphaFold pdb e-kbP35548   
Human Protein Atlas [tissue]ENSG00000120149-MSX2 [tissue]
HPRD00421
Protein Interaction databases
DIP (DOE-UCLA)P35548
IntAct (EBI)P35548
BioGRIDMSX2
STRING (EMBL)MSX2
ZODIACMSX2
Ontologies - Pathways
QuickGOP35548
Ontology : AmiGOnegative regulation of transcription by RNA polymerase II  negative regulation of transcription by RNA polymerase II  chromatin  transcription cis-regulatory region binding  RNA polymerase II transcription regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  osteoblast differentiation  cardiac conduction system development  protein binding  nucleus  cytosol  regulation of transcription by RNA polymerase II  nuclear speck  sequence-specific DNA binding  negative regulation of transcription, DNA-templated  embryonic morphogenesis  cranial suture morphogenesis  sequence-specific double-stranded DNA binding  negative regulation of transcription regulatory region DNA binding  
Ontology : EGO-EBInegative regulation of transcription by RNA polymerase II  negative regulation of transcription by RNA polymerase II  chromatin  transcription cis-regulatory region binding  RNA polymerase II transcription regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  osteoblast differentiation  cardiac conduction system development  protein binding  nucleus  cytosol  regulation of transcription by RNA polymerase II  nuclear speck  sequence-specific DNA binding  negative regulation of transcription, DNA-templated  embryonic morphogenesis  cranial suture morphogenesis  sequence-specific double-stranded DNA binding  negative regulation of transcription regulatory region DNA binding  
Pathways : KEGGHTLV-I infection   
REACTOMEP35548 [protein]
REACTOME PathwaysR-HSA-8939902 [pathway]   
NDEx NetworkMSX2
Atlas of Cancer Signalling NetworkMSX2
Wikipedia pathwaysMSX2
Orthology - Evolution
OrthoDB4488
GeneTree (enSembl)ENSG00000120149
Phylogenetic Trees/Animal Genes : TreeFamMSX2
Homologs : HomoloGeneMSX2
Homology/Alignments : Family Browser (UCSC)MSX2
Gene fusions - Rearrangements
Fusion : QuiverMSX2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMSX2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MSX2
dbVarMSX2
ClinVarMSX2
MonarchMSX2
1000_GenomesMSX2 
Exome Variant ServerMSX2
GNOMAD BrowserENSG00000120149
Varsome BrowserMSX2
ACMGMSX2 variants
VarityP35548
Genomic Variants (DGV)MSX2 [DGVbeta]
DECIPHERMSX2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMSX2 
Mutations
ICGC Data PortalMSX2 
TCGA Data PortalMSX2 
Broad Tumor PortalMSX2
OASIS PortalMSX2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMSX2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMSX2
Mutations and Diseases : HGMDMSX2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutaMSX2
DgiDB (Drug Gene Interaction Database)MSX2
DoCM (Curated mutations)MSX2
CIViC (Clinical Interpretations of Variants in Cancer)MSX2
NCG (London)MSX2
Cancer3DMSX2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM123101    168500    168550    604757   
Orphanet19622    3169    10796   
DisGeNETMSX2
MedgenMSX2
Genetic Testing Registry MSX2
NextProtP35548 [Medical]
GENETestsMSX2
Target ValidationMSX2
Huge Navigator MSX2 [HugePedia]
ClinGenMSX2 (curated)
Clinical trials, drugs, therapy
MyCancerGenomeMSX2
Protein Interactions : CTDMSX2
Pharm GKB GenePA31197
PharosP35548
Clinical trialMSX2
Miscellaneous
canSAR (ICR)MSX2
HarmonizomeMSX2
DataMed IndexMSX2
Probes
Litterature
PubMed95 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXMSX2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:23:01 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.