MSX2

Chr 5

msh homeobox 2

Also known as: CRS2, FPP, HOX8, MSH, PFM, PFM1

NCBI Gene: 4488 ENSG00000120149 UniProt: P35548

The MSX2 protein is a transcriptional repressor that regulates bone development by controlling osteoblast differentiation and has a morphogenetic role in craniofacial development. Mutations cause craniosynostosis type 2, parietal foramina (with or without cleidocranial dysplasia), affecting skull bone formation and closure. The condition follows autosomal dominant inheritance.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtParietal foramina 1

UniProtParietal foramina with cleidocranial dysplasia

UniProtCraniosynostosis 2

Clinical highlights

Gene-disease validity (ClinGen)

parietal foramina · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

LOF

Mechanism· G2P

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GeneReview available — MSX2