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Symbol MSX2 contributors: mct/npt/pgu - updated : 18-09-2015
HGNC name msh homeobox 2
HGNC id 7392
Corresponding disease
CRS2 craniosynostosis, syndromatic 2
DUP5QD chromosome 5q distal duplication
PFM2 parietal foramina permagna 2
Location 5q35.2      Physical location : 174.151.574 - 174.157.901
Synonym name msh homeo box homolog 2 (Drosophila)
Synonym symbol(s) HOX8, HOX-8, Msx-2, PFM1, FPP, MSH, PFM
TYPE functioning gene
STRUCTURE 6.33 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • FOXC1 occupies a conserved element in the MSX2 promoter, and can stimulate the activity of the both human and mouse MSX2 promoters
  • MAPPING cloned Y linked N status confirmed
    Map see D5S2360
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2224 - 267 - 2008 18349132
    Type widely
       expressed in (based on citations)
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivedenseligamentperidontal ligament 
    Epithelialbarrier liningepidermis highly
    cell lineage
    cell lines high in several cell lines
    at STAGE
    physiological period embryo, fetal, pregnancy
  • developing teeth progenitor cells of orofacial skeletal structure (mandible, Meckel's cartilage), extra-embryonic tissues such as placenta
  • in the epidermis, hair follicles, and fibroblasts of the developing fetal skin
  • helix-turn-helix, DNA binding domain
    interspecies homolog to Drosophila,muscle segment (msh) 2
  • MSH homeobox protein family (non HOX)
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    text detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis
    basic FUNCTION
  • involved in the enhancing of parietal bone growth and skull patterning
  • involved in epithelial-mesenchymal signaling in many organs
  • RNA polymerase 2 transcription factor, activating OSX and regulating osteogenic versus adipogenic differentiation of aortic myofibroblasts and of multipotent mesenchymal progenitor
  • involved in maintaining the suture space by stimulating suture mesenchymal cell proliferation
  • plays a pivotal role in craniofacial and limb development and tissue organogenesis
  • major regulator of the proliferation of MSX2-expressing osteoprogenitor cells and subsequent osteoblast differentiation
  • plays a crucial role in pancreatic cancer development by inducing changes consistent with epithelial to mesenchymal transition through enhanced expression of TWIST1
  • could induce apoptosis of optic vesicle
  • possesses dual regulatory functions in controlling cell cycle progression of retinal progenitor cells (RPCs) and timing of retinal ganglion cells differentiation
  • MSX1, MSX2 have a dual role in calvarial development
  • with RUNX2 function together to induce ENPP1 expression in osteoblastic cells
  • functioning as a transcriptional enhancer downstream of FGF2 in calvarial pre-osteoblasts
  • important functions for MSX2 and FOXN1 in regulating differentiation of the keratogenous zone, proliferation of distal nail matrix cells, and organization of the nail bed
  • homeodomain transcription factor that play a crucial role in limb development
  • mesenchymal expression of MSX1 and MSX2 is required for proper SHH and BMP4 signaling to specify digit number and identity
  • MSX1 and MSX2 promote meiosis initiation
  • DLX5 and MSX2 play potentially a critical role in controlling cranial neural tube morphogenesis by regulating cell adhesion via the EPHA5 and EPHA7 pathway
  • CELLULAR PROCESS nucleotide, transcription
  • a FOXC1/MSX2 regulatory network functions in the initial stages of osteoblast differentiation
  • a component
    small molecule
  • interacting with MSX1 in mouse limb bud patterning through BMP4 regulation
  • regulating with TWIST1 the expression of EFNA4
  • inhibits the function of key osteogenic regulators, such as RUNX2, DLX3, and DLX5
  • promotes transcription of ENPP1 downstream of FGF2
  • direct downstream transcriptional target of CTNNB1/TCF and has a key contributing role in the cancer phenotype of ovarian endometrioid adenocarcinomas carrying WNT/CTNNB1 pathway defects
  • DLX3 and DLX5 proteins were found to activate the GPNMB transcription, whereas, MSX2 suppressed BMP2-induced GPNMB transcription
  • TNF enhances the WNT/CTNNB1 signaling pathway by inducing MSX2 expression, which in turn suppresses adipocytic differentiation
  • direct regulatory connection between the neural plate border genes, PAX7 and MSX1/2, and FOXD3, suggesting it is an immediate downstream target
  • AMBN plays a crucial role in the regulation of cranial bone growth and suture closure via MSX2 suppression and proliferation inhibition
  • expression of MSX2 was down-regulated by HR, which in turn down-regulated expression of FOXN1 and LEF1, MSX2 target genes
  • MSX2 controls mesendoderm lineage commitment by simultaneous suppression of SOX2 and induction of NODAL expression through direct binding and activation of the NODAL promoter
  • complex feedback regulatory network may exist between BCL11B and MSX2
  • cell & other
    induced by bone morphogenetic proteins
    Other affinity for DNA enhanced by PSIAX (MIZ1)
    corresponding disease(s) CRS2 , PFM2 , DUP5QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    various tumors of mesenchymal origin
    tumoral     --over  
    significantly correlated with higher tumor grade, vascular invasion, and TWIST1 expression
    tumoral     --other  
    aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia
    constitutional     --over  
    regulated retinal cells by affecting cell cycle and proliferation and caused delay in retinal ganglion cell commitment and differentiation
    constitutional       loss of function
    inactivation of its repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised
    tumoral     --over  
    markedly increased in primary human and murine OEAs with dysregulated CTNNB1compared with ovarian endometrioid adenocarcinoma with intact CTNNB1regulation
    Susceptibility to ankylosing spondylitis
    Variant & Polymorphism SNP increasing the risk of ankylosing spondylitis
    Candidate gene in cranial vault morphogenesis, sensitive to gene dosage; in cleft lip/palate
  • it is possible to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis by evaluating MSX2 expression level
  • Therapy target
  • defects in bone growth and ectodermal organ formation in Msx2 deficient mice, premature cranial suture closure
  • expression of the Msx2 homeobox gene, an essential regulator of calvarial bone development is absent in the skull mesenchymal progenitors of Foxc1 mutant mice
  • Msx1;Msx2 double mutants are characterized by the loss of derivatives of the anterior limb mesoderm which is not observed in either of the simple mutants