InterPro: IPR003993 Treacher Collins syndrome, treacle

Treacher Collins Syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate [1, 2]; it is the most common of the human mandibulo-facial dysostosis disorders [1]. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) [2]. To date, 35 mutations have been reported in TCOF1, all but one of which result in the introduction of a premature-termination codon into the predicted protein, Treacle. The observed mutational spectrum supports the hypothesis that TCS results from haploinsufficiency.

Treacle is a low complexity protein of 1,411 amino acids whose predicted protein structure contains a set of highly polar repeated motifs [1]. These motifs are common to nucleolar trafficking proteins in other species and are predicted to be phosphorylated by casein kinase. In concert with this observation, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localisation signals [1]. Throughout the open reading frame are found mutations in TCS families and several polymorphisms. It has thus been suggested that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.