TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region

Carol A. Wise, Lydia C. Chiang, William A. Paznekas, Mridula Sharma, Maurice M. Musy, Jennifer A. Ashley, Michael Lovett, Ethylin W. Jabs

Research output: Contribution to journalArticle

109 Scopus citations


Treacher Collins Syndrome (TCS) is the most common of the human mandibulofacial dysostosis disorders. Recently, a partial TCOF1 cDNA was identified and shown to contain mutations in TCS families. Here we present the entire exon/intron genomic structure and the complete coding sequence of TCOF1. TCOF1 encodes a low complexity protein of 1,411 amino acids, whose predicted protein structure reveals repeated motifs that mirror the organization of its exons. These motifs are shared with nucleolar trafficking proteins in other species and are predicted to be highly phosphorylated by casein kinase. Consistent with this, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localization signals. Throughout the open reading frame, we detected an additional eight mutations in TCS families and several polymorphisms. We postulate that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.

Original languageEnglish (US)
Pages (from-to)3110-3115
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
Publication statusPublished - Apr 1 1997


ASJC Scopus subject areas

  • Genetics
  • General

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