This gene encodes a member of the muscle segment
homeobox gene family. The encoded protein functions as a transcriptional repressor during
embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation,
craniofacial development, in particular,
odontogenesis, and tumor growth inhibition. There is also strong evidence from sequencing studies of candidate genes involved in clefting that mutations in the MSX1 gene may be associated in the pathogenesis of
cleft lip and palate. Mutations in this gene, which was once known as homeobox 7, have also been associated with
Witkop syndrome,
Wolf–Hirschhorn syndrome, and autosomal dominant
hypodontia. Haploinsufficiency of MSX1 protein affects the development of all teeth, preferentially third molars and second premolars. The effect of haploinsufficiency of PAX9 on the development of incisors and premolars is probably caused by a deficiency of MSX1 protein.
Phenotypes caused by deficiency of MSX1 protein might depend on the localization of mutations and their effect on the protein structure and function. Two substitution mutations, Arg196Pro and Met61Lys cause only familial non-syndromic tooth agenesis. Frameshift mutations, Ser202Stop mutation, resulting in a protein that lacks the C-terminal end of the homeodomain, impairs not only teeth but also nail formation, while Ser105Stop mutation, causing complete absence of the MSX1 homeodomain, is responsible for the most severe phenotype, which includes orofacial clefts with accompanied tooth agenesis. == Interactions ==