MSX2: A Key Regulator in Craniofacial Development and Disease
Comprehensive genomic and proteomic overview of the MSX2 gene, its expression, mutations, and clinical significance.
Gene Information Card
| Symbol | MSX2 |
|---|---|
| Full Name | msh homeobox 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q35.2 |
| NCBI Gene ID | 4488 ncbi.nlm.nih.gov/gene/4488 |
| Ensembl ID | ENSG00000120162 |
| UniProt ID | P35548 |
| OMIM ID | 123101 |
| HGNC ID | 7392 |
| Aliases | PFM3, HOX8, MSH, FPP, CRS2 |
Description
MSX2 (msh homeobox 2) is a protein-coding gene that encodes a member of the muscle segment homeobox gene family. The encoded transcription factor plays a critical role in craniofacial development, particularly in the regulation of bone formation and suture closure. Mutations in MSX2 are associated with craniosynostosis type 2 (CRS2) and parietal foramina (PFM). The protein functions as a transcriptional repressor during development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Craniosynostosis type 2 (CRS2) | Gain-of-function mutations in MSX2 enhance DNA binding and transcriptional repression, leading to premature fusion of cranial sutures. | ClinVar, OMIM #123101 |
| Parietal foramina (PFM) | Loss-of-function or dominant-negative mutations impair MSX2 activity, resulting in defective ossification of parietal bones. | ClinVar, OMIM #168500 |
| Orofacial clefting | MSX2 variants may contribute to non-syndromic cleft lip/palate through disrupted craniofacial patterning. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 12.5 | Medium |
| Heart | 8.3 | Low |
| Brain | 6.1 | Low |
| Lung | 4.7 | Low |
| Kidney | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| hTERT-HME1 (mammary epithelial) | 15.2 | Moderate expression |
| U-2 OS (osteosarcoma) | 22.8 | High expression |
| MCF7 (breast cancer) | 5.1 | Low expression |
| HepG2 (liver cancer) | 2.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.650A>G (p.Asn217Ser) | Missense | Rare | Gain-of-function; associated with craniosynostosis type 2 |
| c.452C>T (p.Pro151Leu) | Missense | Rare | Loss-of-function; associated with parietal foramina |
| c.1A>G (p.Met1?) | Start loss | Very rare | Likely loss-of-function; reported in craniofacial defects |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Pro151Leu reduce DNA-binding affinity or protein stability, leading to haploinsufficiency and parietal foramina.
Gain of Function (GOF)
Mutations such as p.Asn217Ser increase transcriptional repression activity, causing premature suture fusion in craniosynostosis.
Dominant Negative (DN)
Some missense variants may interfere with wild-type MSX2 function, contributing to parietal foramina phenotype.
View complete mutation data：
Gene Ontology (GO)
Pathways
• BMP signaling pathway (Reactome: R-HSA-201451)
• Transcriptional regulation by MSX2 (PMID: 10835629)
Protein Summary
The MSX2 protein (UniProt P35548) is a 267-amino-acid homeobox transcription factor that localizes to the nucleus. It contains a highly conserved homeodomain that mediates sequence-specific DNA binding. MSX2 acts primarily as a transcriptional repressor, modulating genes involved in osteoblast differentiation and cranial suture morphogenesis. Post-translational modifications include phosphorylation, which may regulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSX2 Knockout HEK293 Cell Line | EDJ-KQ2925 | Human | 4488 | Details Get a Quote |
| MSX2 Knockout A-549 Cell Line | EDJ-KQ24025 | Human | 4488 | Details Get a Quote |
| MSX2 Knockout HCT 116 Cell Line | EDJ-KQ24026 | Human | 4488 | Details Get a Quote |
| MSX2 Knockout HeLa Cell Line | EDJ-KQ24027 | Human | 4488 | Details Get a Quote |
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