Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

MSX2

contributors: mct/npt/pgu - updated : 18-09-2015

HGNC name	msh homeobox 2
HGNC id	7392

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002449 2 - 2224 NP_002440 - 267 - 2008 18349132

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Connective dense ligament peridontal ligament   Connective dense tendon     Epithelial barrier lining epidermis   highly

cell lineage
cell lines	high in several cell lines
fluid/secretion

at STAGE

physiological period

embryo, fetal, pregnancy

Text	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

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

helix-turn-helix, DNA binding domain

HOMOLOGY

interspecies

homolog to Drosophila,muscle segment (msh) 2

Homologene

FAMILY

MSH homeobox protein family (non HOX)

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,chromatin/chromosome
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

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a FOXC1/MSX2 regulatory network functions in the initial stages of osteoblast differentiation

a component

INTERACTION

DNA

RNA

small molecule

protein	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

REGULATION

induced by

bone morphogenetic proteins

Other

affinity for DNA enhanced by PSIAX (MIZ1)

ASSOCIATED DISORDERS

corresponding disease(s)

CRS2 , PFM2 , DUP5QD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
Marker	it is possible to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis by evaluating MSX2 expression level
Therapy target

ANIMAL & CELL MODELS

	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