TCOF1

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.{{Cite web |title=Chromosome 5: 150,357,629-150,400,308 - Region in detail - Homo_sapiens - Ensembl genome browser 113 |url=https://asia.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000070814;r=5:150357629-150400308 |access-date=2025-02-26 |website=asia.ensembl.org}}

TCOF1 is involved in the production of a molecule called ribosomal RNA (rRNA) within cells. TCOF1 is active in the nucleolus, which is a small region inside the nucleus where rRNA is produced.{{cite journal | vauthors = Wise CA, Chiang LC, Paznekas WA, Sharma M, Musy MM, Ashley JA, Lovett M, Jabs EW | title = TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 7 | pages = 3110–3115 | date = April 1997 | pmid = 9096354 | pmc = 20330 | doi = 10.1073/pnas.94.7.3110 }} As a major component of cell structures called ribosomes, rRNA is essential for the assembly of proteins.{{Cite web |title=Ribosomes, Transcription, Translation {{!}} Learn Science at Scitable |url=https://www.nature.com/scitable/topicpage/ribosomes-transcription-and-translation-14120660/ |access-date=2025-02-25 |website=www.nature.com |language=en}} This protein is active during early embryonic development in structures that become bones and other tissues in the face.{{Cite web |title=TCOF1 gene: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/gene/tcof1/ |access-date=2025-02-25 |website=medlineplus.gov |language=en}} 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.{{cite journal | vauthors = Dixon J, Jones NC, Sandell LL, Jayasinghe SM, Crane J, Rey JP, Dixon MJ, Trainor PA | title = Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 36 | pages = 13403–13408 | date = September 2006 | pmid = 16938878 | doi = 10.1073/pnas.0603730103 | pmc = 1557391 }}

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.{{cite journal | vauthors = Gonzales B, Henning D, So RB, Dixon J, Dixon MJ, Valdez BC | title = The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation | journal = Human Molecular Genetics | volume = 14 | issue = 14 | pages = 2035–2043 | date = July 2005 | pmid = 15930015 | doi = 10.1093/hmg/ddi208 | doi-access = free }}

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.{{cite journal | vauthors = Dixon MJ, Marazita ML, Beaty TH, Murray JC | title = Cleft lip and palate: understanding genetic and environmental influences | journal = Nature Reviews. Genetics | volume = 12 | issue = 3 | pages = 167–78 | date = March 2011 | pmid = 21331089 | pmc = 3086810 | doi = 10.1038/nrg2933 }}

Mutations in this gene in Jindo dogs have been associated to the observed cranial differences between Jindo and boxer dogs.{{cite journal | vauthors = Kim RN, Kim DS, Choi SH, Yoon BH, Kang A, Nam SH, Kim DW, Kim JJ, Ha JH, Toyoda A, Fujiyama A, Kim A, Kim MY, Park KH, Lee KS, Park HS | title = Genome analysis of the domestic dog (Korean Jindo) by massively parallel sequencing | journal = DNA Research | volume = 19 | issue = 3 | pages = 275–287 | date = June 2012 | pmid = 22474061 | pmc = 3372376 | doi = 10.1093/dnares/dss011 }}

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• {{cite journal | vauthors = Edwards SJ, Gladwin AJ, Dixon MJ | title = The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon | journal = American Journal of Human Genetics | volume = 60 | issue = 3 | pages = 515–524 | date = March 1997 | pmid = 9042910 | pmc = 1712503 }}
• {{cite journal | vauthors = Dixon J, Edwards SJ, Anderson I, Brass A, Scambler PJ, Dixon MJ | title = Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene | journal = Genome Research | volume = 7 | issue = 3 | pages = 223–234 | date = March 1997 | pmid = 9074926 | doi = 10.1101/gr.7.3.223 | doi-access = free }}
• {{cite journal | vauthors = Wise CA, Chiang LC, Paznekas WA, Sharma M, Musy MM, Ashley JA, Lovett M, Jabs EW | title = TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 7 | pages = 3110–3115 | date = April 1997 | pmid = 9096354 | pmc = 20330 | doi = 10.1073/pnas.94.7.3110 | doi-access = free | bibcode = 1997PNAS...94.3110W }}
• {{cite journal | vauthors = Paznekas WA, Zhang N, Gridley T, Jabs EW | title = Mouse TCOF1 is expressed widely, has motifs conserved in nucleolar phosphoproteins, and maps to chromosome 18 | journal = Biochemical and Biophysical Research Communications | volume = 238 | issue = 1 | pages = 1–6 | date = September 1997 | pmid = 9299440 | doi = 10.1006/bbrc.1997.7229 | doi-access = free }}
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• {{cite journal | vauthors = Marsh KL, Dixon J, Dixon MJ | title = Mutations in the Treacher Collins syndrome gene lead to mislocalization of the nucleolar protein treacle | journal = Human Molecular Genetics | volume = 7 | issue = 11 | pages = 1795–1800 | date = October 1998 | pmid = 9736782 | doi = 10.1093/hmg/7.11.1795 | doi-access = free }}
• {{cite journal | vauthors = Winokur ST, Shiang R | title = The Treacher Collins syndrome (TCOF1) gene product, treacle, is targeted to the nucleolus by signals in its C-terminus | journal = Human Molecular Genetics | volume = 7 | issue = 12 | pages = 1947–1952 | date = November 1998 | pmid = 9811939 | doi = 10.1093/hmg/7.12.1947 | doi-access = free }}
• {{cite journal | vauthors = Jones NC, Farlie PG, Minichiello J, Newgreen DF | title = Detection of an appropriate kinase activity in branchial arches I and II that coincides with peak expression of the Treacher Collins syndrome gene product, treacle | journal = Human Molecular Genetics | volume = 8 | issue = 12 | pages = 2239–2245 | date = November 1999 | pmid = 10545604 | doi = 10.1093/hmg/8.12.2239 | doi-access = free }}
• {{cite journal | vauthors = Isaac C, Marsh KL, Paznekas WA, Dixon J, Dixon MJ, Jabs EW, Meier UT | title = Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome | journal = Molecular Biology of the Cell | volume = 11 | issue = 9 | pages = 3061–3071 | date = September 2000 | pmid = 10982400 | pmc = 14975 | doi = 10.1091/mbc.11.9.3061 }}
• {{cite journal | vauthors = Emes RD, Ponting CP | title = A new sequence motif linking lissencephaly, Treacher Collins and oral-facial-digital type 1 syndromes, microtubule dynamics and cell migration | journal = Human Molecular Genetics | volume = 10 | issue = 24 | pages = 2813–2820 | date = November 2001 | pmid = 11734546 | doi = 10.1093/hmg/10.24.2813 | doi-access = free }}
• {{cite journal | vauthors = Splendore A, Jabs EW, Passos-Bueno MR | title = Screening of TCOF1 in patients from different populations: confirmation of mutational hot spots and identification of a novel missense mutation that suggests an important functional domain in the protein treacle | journal = Journal of Medical Genetics | volume = 39 | issue = 7 | pages = 493–495 | date = July 2002 | pmid = 12114482 | pmc = 1735178 | doi = 10.1136/jmg.39.7.493 }}
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• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tcs GeneReviews/NCBI/NIH/UW entry on Treacher Collins Syndrome or Mandibulofacial Dysostosis]
• [https://www.genecards.org/cgi-bin/carddisp?TCOF1 GeneCard]
• {{MeshName|TCOF1+protein,+human}}
• {{UCSC genome browser|TCOF1}}
• {{UCSC gene details|TCOF1}}

{{Nucleus}}

{{DEFAULTSORT:Treacle Protein}}