TBX15

From Proteopedia

1 Introduction
2 Functions and pathways of TBX15
3 Known malfunctional mutations
4 3D Structures
5 Additional Resources

Introduction

TBX15 is implicated in Cousin syndrome. Cousin syndrome was first discovered in humans. Tbx15 deficiency in mice were isolated, and were seen to have similar symptoms. DNA of two girls with Cousin syndrome were searched directly for TBX15 deficiency or mutations and two related mutations were discovered. The mutant mRNA was present at a level same or higher than that of wild-type mRNA, and the expressed protein had a lower stability than the wild-type TBX15.

Functions and pathways of TBX15

Target genes of TBX15 are so far elusive but are believed to be possibly shared with those of SOX9, FGFR2 and POR.

Known malfunctional mutations

The two related mutations discovered by sequencing Cousin syndrome sufferers were

Deletion at codon 344 resulting in a frame shift of the remaining 78 amino acids
Deletion resulting in a frame shift of remaining 77 amino acids

On checking the stability and localisation of the TBX15 mutants, it was found that it was no longer targetted to the nucleus. Simple truncation of the C-terminal 152 amino acids does not affect stability alone; however, presence of the missense 78 amino acids target the protein to proteasomal degradation, suggesting the mutant is an inherently unstable protein. This was confirmed by fusing EGFP (enhanced green fluorescent protein) to the mutant TBX15 on its C-terminus, which was found to be undetectable in cells.

It is possible, but not confirmed, that dominant mutations in the T-box region of TBX15 may correspond to a Kosenow syndrome phenotype, a candidate disease.