TCOF1

Treacle Ribosome Biogenesis Factor 1 (TCOF1) also known as Treacle is a protein that in humans is encoded by the TCOF1 gene.^[5][6] TCOF1 encodes a nucleolar protein with an LIS1 homology domain.^[7] The treacle protein is involved in rRNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Alternate transcriptional splice variants encoding different isoforms have been found for this gene, but only three of them have been characterized to date.^[6]

TCOF1
Identifiers
Aliases	TCOF1, MFD1, TCS, TCS1, treacle, treacle ribosome biogenesis factor 1
External IDs	OMIM: 606847; MGI: 892003; HomoloGene: 68049; GeneCards: TCOF1; OMA:TCOF1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q32-q33.1 Start 150,357,629 bp[1] End 150,400,308 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E1|18 34.41 cM Start 60,946,827 bp[2] End 60,982,043 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve oocyte dorsal motor nucleus of vagus nerve granulocyte pericardium lymph node pylorus apex of heart tendon of biceps brachii gonad Top expressed in tail of embryo internal carotid artery epiblast otic vesicle thymus external carotid artery genital tubercle otic placode yolk sac Rostral migratory stream More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding transporter activity RNA binding RNA polymerase I core binding protein heterodimerization activity scaffold protein binding Cellular component nucleolus nucleus fibrillar center cytosol Biological process skeletal system development regulation of translation neural crest formation neural crest cell development transport nucleolar large rRNA transcription by RNA polymerase I Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6949 21453 Ensembl ENSG00000070814 ENSMUSG00000024613 UniProt Q13428 O08784 RefSeq (mRNA) NM_000356 NM_001008656 NM_001008657 NM_001135243 NM_001135244 NM_001135245 NM_001195141 NM_001371623 NM_001198984 NM_011552 RefSeq (protein) NP_000347 NP_001008657 NP_001128715 NP_001128716 NP_001128717 NP_001182070 NP_001358552 NP_001185913 NP_035682 Location (UCSC) Chr 5: 150.36 – 150.4 Mb Chr 18: 60.95 – 60.98 Mb PubMed search [3] [4]
Wikidata
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Gene

The TCOF1 gene is located on the long (q) arm of chromosome 5 between positions 32 and 33.1, from base pair 150,357,629 to base pair 150,400,308.^[8]

Function

TCOF1 is involved in the production of a molecule called ribosomal RNA (rRNA) within cells.^[7] TCOF1 is active in the nucleolus, which is a small region inside the nucleus where rRNA is produced.^[9] As a major component of cell structures called ribosomes, rRNA is essential for the assembly of proteins.^[10] This protein is active during early embryonic development in structures that become bones and other tissues in the face.^[11] Although the precise function of this protein is unknown, researchers believe that it plays a critical role in the development of facial bones and related structures.^[12]

Aside from its interaction with UBF, treacle has been implicated in the methylation of the precursor to mature ribosomal RNA by interaction with the nucleolar protein pNop56.^[13]

Clinical significance

More than 120 mutations in the TCOF1 gene have been identified in people with Treacher Collins syndrome. Most of these mutations insert or delete a small number of DNA building blocks (base pairs) in the TCOF1 gene. TCOF1 mutations lead to the production of an abnormally small, nonfunctional version of treacle or prevent the cell from producing this protein. Researchers speculate that a loss of treacle reduces the production of rRNA in parts of the embryo that develop into facial bones and tissues. It is not known how loss of the treacle protein causes the specific problems with facial development found in Treacher Collins syndrome. For instance, mutations in the TCOF gene of these individuals often result in a cleft palate.^[14]

Model organisms

Mutations in this gene in Jindo dogs have been associated to the observed cranial differences between Jindo and boxer dogs.^[15]