MSX2

Protein identityUniProt · HPA

UniProt accession

P35548

Gene

MSX2

Ensembl

ENSG00000120149

Chromosome

5

Canonical length

267 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors

Subcellular location

Nuclear speckles

OverviewNCBI Gene

This gene encodes a member of the muscle segment homeobox gene family. The encoded protein is a transcriptional repressor whose normal activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis. The encoded protein may also have a role in promoting cell growth under certain conditions and may be an important target for the RAS signaling pathways. Mutations in this gene are associated with parietal foramina 1 and craniosynostosis type 2. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

267 residues, UniProt reviewed canonical sequence.

>P35548|MSX2
     1  MASPSKGNDL FSPDEEGPAV VAGPGPGPGG AEGAAEERRV KVSSLPFSVE ALMSDKKPPK
    61  EASPLPAESA SAGATLRPLL LSGHGAREAH SPGPLVKPFE TASVKSENSE DGAAWMQEPG
   121  RYSPPPRHMS PTTCTLRKHK TNRKPRTPFT TSQLLALERK FRQKQYLSIA ERAEFSSSLN
   181  LTETQVKIWF QNRRAKAKRL QEAELEKLKM AAKPMLPSSF SLPFPISSPL QAASIYGASY
   241  PFHRPVLPIP PVGLYATPVG YGMYHLS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MSX2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.65

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MSX2.

Disease | AllUniProt

Conditions MSX2 is implicated in, by any mechanism.

• Parietal foramina 1 (PFM1) MIM:168500
• Parietal foramina with cleidocranial dysplasia (PFMCCD) MIM:168550
• Craniosynostosis 2 (CRS2) MIM:604757

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 268 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Parietal foramina 1
• Craniosynostosis 2
• Enlarged Parietal Foramina
• Parietal foramina with cleidocranial dysplasia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.82

gnomAD pLI

0.26

gnomAD missense Z

0.47

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of meiosis
• anterior/posterior pattern specification
• BMP signaling pathway
• bone trabecula formation
• branching involved in mammary gland duct morphogenesis
• cardiac conduction system development
• cell surface receptor signaling pathway involved in heart development
• cellular response to estradiol stimulus
• chondrocyte development
• cranial suture morphogenesis
• embryonic forelimb morphogenesis
• embryonic hindlimb morphogenesis
• embryonic morphogenesis
• embryonic nail plate morphogenesis
• enamel mineralization
• endochondral bone growth
• epithelial to mesenchymal transition involved in endocardial cushion formation
• frontal suture morphogenesis
• mesenchymal cell apoptotic process
• negative regulation of apoptotic process
• negative regulation of cell population proliferation
• negative regulation of DNA-templated transcription
• negative regulation of fat cell differentiation
• negative regulation of keratinocyte differentiation
• negative regulation of transcription by RNA polymerase II
• osteoblast development
• osteoblast differentiation
• outflow tract septum morphogenesis
• positive regulation of BMP signaling pathway
• positive regulation of mesenchymal cell apoptotic process
• positive regulation of osteoblast differentiation
• positive regulation of timing of catagen
• regulation of transcription by RNA polymerase II
• signal transduction involved in regulation of gene expression
• stem cell differentiation
• wound healing, spreading of epidermal cells

Molecular functions

• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• transcription cis-regulatory region binding

Cellular components

• chromatin
• cytosol
• nuclear speck
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Homedomain-like superfamily
• Homeobox, conserved site
• Homeodomain, metazoa
• Msh Homeobox Transcriptional Regulators
• Homeodomain

KeywordsUniProt

• Craniosynostosis
• Developmental protein
• DNA-binding
• Homeobox
• Nucleus
• Osteogenesis
• Repressor
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of MSX2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MINT
• XRCC6
• SPEN
• MAGED1
• ROR2