Domain

Treacher Collins syndrome, treacle (IPR003993)

Short name: TCS_treacle

Domain relationships

None.

Description

Treacher Collins Syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate [PMID: 9096354, PMID: 9042910]; it is the most common of the human mandibulo-facial dysostosis disorders [PMID: 9096354]. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) [PMID: 9042910]. 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 [PMID: 9096354]. 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 [PMID: 9096354]. 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.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam