| Primary Identifier | IPR003993 | Type | Domain |
| Short Name | Treacle_dom |
| description | Treacher Collins Syndrome (TCS) is an autosomal dominant disorder ofcraniofacial development, the features of which include conductive hearing loss and cleft palate [, ]; it is the most common of the human mandibulo-facial dysostosis disorders []. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) []. 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 predictedprotein structure contains a set of highly polar repeated motifs []. 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 []. Throughout the openreading 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. |
