Table 1.
Summary of PAX9 paired domain mutations, functional and predicted structural consequences and tooth phenotypes
| Mutation | Subcellular localization | Protein stabilitya | DNA binding-EMSAb | Trans-activation | Trans-activation+MSX1 | MSX1 binding-colpc | Predicted structural alteration | Tooth phenotyped | Severity, average no. of missing teeth | References |
|---|---|---|---|---|---|---|---|---|---|---|
| 219insG | Cytoplasm | Intact N-term SD only | – | Not detectable | Not detectable | N/D | Frameshift in linker; N-term SD only intact | Oligodontia M, P, Cl | Moderate 10 | Stockton et al. (2000); Mensah et al. (23) |
| Gly6Arg | Nucleus | +10.5% | ++++ | Moderate | Increased | + | Minimal, at surface | Hypodontia P, Cl | Mild 3 | Wang et al. (2008) |
| Leu21 Pro | Nucleus* | −0.9% | – | Negligible | Negligible | + | Steric clash with DNA | Oligodontia M, P, C, Cl, LI | Moderate 10 | Das et al. (7); Ogawa et al. (10) |
| Arg26TRP | Nucleus* | −17.8% | – | Negligible | Negligible | + | Instability and DNA contact loss | Oligodontia M, P, C, Cl, LI | Severe 11.3 | Lammil et al. (2003) |
| Arg28Pro | Nucleus* | −13.0% | −/+ | Negligible | Negligible | + | Instability, α2 kinked | Oligodontia M, P, C, Cl | Severe 13 | Jumlongras et al. (13) |
| Ser43Lys | Nucleus* | −7.4% | + | Negligible | Negligible | + | Instability, DNA clash | Oligodontia M, P, C | Mild 6.5 | Wang et al. (2008) |
| Gly51Ser | Nucleus | +2.5% | +++ | Enhanced | No increased | + | Context-dependent | Oligodontia P, C, Cl, LI | Moderate 9 | Mostowska et al. (15) |
| Ile87Phe | Nucleus* | −5.2% | −/+ | Negligible | Increased | + | C-term SD instability | Oligodontia M, P | Severe 11.5 | Kapadia et al. (11) |
| Lys91Glu | Nucleus | +0.2% | +++ | Negligible | Increased | + | Water/DNA binding | Oligodontia M, P, C, Cl, LI | moderate 8.4 | Das et al. (7) |
aProtein stability calculated by modeling routine as a total energy term for individual N- and C-terminal subdomains with Gly72 (C) and Gly73 (N) as terminal residues.
bEMSA, electrophoretic mobility shift assay; wild-type PAX9 binding would be +++++ by comparison.
ccolP, co-immunoprecipitation: wild-type PAX9 binding, +.
dCI central ineisor, LI laterla ineisor, C canine, P first or second premolar, M first or second molar—nomenclature and table after Jumlongras et al. (2004). Note the primary tooth development was unaffected by all of the missense mutation, however the 219insG frameshift mutation was associated with one or more missing primary molars. Nuclear localized mutation also detected in trace amounts in cytoplasmic fractions are designated with an asterisk.