Menu
Home
People
Places
Arts
History
Plants & Animals
Science
Life & Culture
Technology
Reference.org
PITX1
open-in-new
<h2 id="function">Function</h2> <p>This gene encodes a member of the RIEG/PITX <a href="/facts/Homeobox/bpvuuw3v">homeobox</a> family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and <a href="/facts/Left-right_asymmetry/s2RrIfVM">left-right asymmetry</a>. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="clinical-relevance">Clinical relevance</h2> <p>Mutations in this gene have been associated with <a href="/facts/Autism/6MTwMNoJ">autism</a>,<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> <a href="/facts/Club_foot/rhmxPQvv">club foot</a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> and <a href="/facts/Polydactyly/jCqalu8P">polydactyly</a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> in humans. </p> <h2 id="genetic-basis-of-pathologies">Genetic basis of pathologies</h2> <p>Genomic rearrangements at the PITX1 locus are associated with <a href="/facts/Liebenberg_syndrome/MWFHTgI1">Liebenberg syndrome</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> In PITX1 Liebenberg is associated with a <a href="/facts/Chromosomal_translocation/MKEwqpQw">translocation</a> or <a href="/facts/Deletion_(genetics)/6TRPY0ys">deletions</a>, which cause insert promoter groups into the PITX1 locus.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> A <a href="/facts/Missense_mutation/uKQ9dC22">missense</a> mutation within the PITX1 locus is associated with the development of autosomal dominant clubfoot.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>PITX1 has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/Pituitary-specific_positive_transcription_factor_1/G8sJorHn">pituitary-specific positive transcription factor 1</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Shang J, Luo Y, Clayton DA (June 1997). "Backfoot is a novel homeobox gene expressed in the mesenchyme of developing hind limb". <i>Developmental Dynamics</i>. 209 (2): 242–53. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2F%28SICI%291097-0177%28199706%29209%3A2%3C242%3A%3AAID-AJA10%3E3.0.CO%3B2-0">10.1002/(SICI)1097-0177(199706)209:2<242::AID-AJA10>3.0.CO;2-0</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9186059">9186059</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:46565338">46565338</a>.</li> <li>Poulin G, Turgeon B, Drouin J (November 1997). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC232521">"NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene"</a>. <i>Molecular and Cellular Biology</i>. 17 (11): 6673–82. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1128%2Fmcb.17.11.6673">10.1128/mcb.17.11.6673</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC232521">232521</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9343431">9343431</a>.</li> <li>Tremblay JJ, Drouin J (April 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84049">"Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription"</a>. <i>Molecular and Cellular Biology</i>. 19 (4): 2567–76. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1128%2Fmcb.19.4.2567">10.1128/mcb.19.4.2567</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84049">84049</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10082522">10082522</a>.</li> <li>Tremblay JJ, Marcil A, Gauthier Y, Drouin J (June 1999). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171422">"Ptx1 regulates SF-1 activity by an interaction that mimics the role of the ligand-binding domain"</a>. <i>The EMBO Journal</i>. 18 (12): 3431–41. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Femboj%2F18.12.3431">10.1093/emboj/18.12.3431</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171422">1171422</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10369682">10369682</a>.</li> <li>Pellegrini-Bouiller I, Manrique C, Gunz G, Grino M, Zamora AJ, Figarella-Branger D, Grisoli F, Jaquet P, Enjalbert A (June 1999). <a href="https://doi.org/10.1210%2Fjcem.84.6.5760">"Expression of the members of the Ptx family of transcription factors in human pituitary adenomas"</a>. <i>The Journal of Clinical Endocrinology and Metabolism</i>. 84 (6): 2212–20. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fjcem.84.6.5760">10.1210/jcem.84.6.5760</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10372733">10372733</a>.</li> <li>Tahara S, Kurotani R, Sanno N, Takumi I, Yoshimura S, Osamura RY, Teramoto A (October 2000). <a href="https://doi.org/10.1038%2Fmodpathol.3880204">"Expression of pituitary homeo box 1 (Ptx1) in human non-neoplastic pituitaries and pituitary adenomas"</a>. <i>Modern Pathology</i>. 13 (10): 1097–108. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fmodpathol.3880204">10.1038/modpathol.3880204</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11048804">11048804</a>.</li> <li>Quentien MH, Manfroid I, Moncet D, Gunz G, Muller M, Grino M, Enjalbert A, Pellegrini I (November 2002). <a href="https://doi.org/10.1074%2Fjbc.M207824200">"Pitx factors are involved in basal and hormone-regulated activity of the human prolactin promoter"</a>. <i>The Journal of Biological Chemistry</i>. 277 (46): 44408–16. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M207824200">10.1074/jbc.M207824200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12223489">12223489</a>.</li> <li>Ghosh AK, Majumder M, Steele R, Ray R, Ray RB (February 2003). <a href="https://doi.org/10.1016%2FS0042-6822%2802%2900029-6">"Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1"</a>. <i>Virology</i>. 306 (1): 51–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0042-6822%2802%2900029-6">10.1016/S0042-6822(02)00029-6</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12620797">12620797</a>.</li> <li>Hiroi N, Kino T, Bassett M, Rainey WE, Phung M, Abu-Asab M, Fojo T, Briata P, Chrousos GP, Bornstein SR (May 2003). "Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase". <i>Hormone and Metabolic Research</i>. 35 (5): 273–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1055%2Fs-2003-41301">10.1055/s-2003-41301</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12915995">12915995</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:260168691">260168691</a>.</li> <li>Kolfschoten IG, van Leeuwen B, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Voorhoeve PM, Agami R (June 2005). "A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity". <i>Cell</i>. 121 (6): 849–58. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.cell.2005.04.017">10.1016/j.cell.2005.04.017</a>. <a href="/facts/Hdl_(identifier)/rdebSxmC">hdl</a>:<a href="https://hdl.handle.net/1874%2F17813">1874/17813</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15960973">15960973</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:18065721">18065721</a>.</li> <li>Lord RV, Brabender J, Wickramasinghe K, DeMeester SR, Holscher A, Schneider PM, Danenberg PV, DeMeester TR (November 2005). "Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma". <i>Surgery</i>. 138 (5): 924–31. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.surg.2005.05.007">10.1016/j.surg.2005.05.007</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16291394">16291394</a>.</li> <li>Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). <a href="https://doi.org/10.1016%2Fj.cell.2006.09.026">"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks"</a>. <i>Cell</i>. 127 (3): 635–48. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.cell.2006.09.026">10.1016/j.cell.2006.09.026</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17081983">17081983</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:7827573">7827573</a>.</li> <li>Picard C, Azeddine B, Moldovan F, Martel-Pelletier J, Moreau A (September 2007). "New emerging role of pitx1 transcription factor in osteoarthritis pathogenesis". <i>Clinical Orthopaedics and Related Research</i>. 462: 59–66. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1097%2FBLO.0b013e3180d09d9c">10.1097/BLO.0b013e3180d09d9c</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17549029">17549029</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:8232057">8232057</a>.</li> <li>Qi DL, Ohhira T, Fujisaki C, Inoue T, Ohta T, Osaki M, Ohshiro E, Seko T, Aoki S, Oshimura M, Kugoh H (April 2011). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126332">"Identification of PITX1 as a TERT suppressor gene located on human chromosome 5"</a>. <i>Molecular and Cellular Biology</i>. 31 (8): 1624–36. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1128%2FMCB.00470-10">10.1128/MCB.00470-10</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126332">3126332</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/21300782">21300782</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=PITX1+protein%2C+human">PITX1+protein,+human</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li> <li><a href="http://omim.org/entry/602149">http://omim.org/entry/602149</a> at OMIM, holds the most up to date information on PITX1.</li> <li><a href="https://ghr.nlm.nih.gov/gene/PITX1">https://ghr.nlm.nih.gov/gene/PITX1</a> at the NIH, has a summary on the effects of PITX1 mutations.</li></ul></li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Crawford MJ, Lanctôt C, Tremblay JJ, Jenkins N, Gilbert D, Copeland N, Beatty B, Drouin J (1997). "Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome". Mammalian Genome. 8 (11): 841–5. CiteSeerX 10.1.1.326.9619. doi:10.1007/s003359900589. PMID 9337397. S2CID 8557603. <a href="/wiki/CiteSeerX_(identifier)" target="_blank">/wiki/CiteSeerX_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Shang J, Li X, Ring HZ, Clayton DA, Francke U (February 1997). "Backfoot, a novel homeobox gene, maps to human chromosome 5 (BFT) and mouse chromosome 13 (Bft)". Genomics. 40 (1): 108–13. doi:10.1006/geno.1996.4558. PMID 9070926. <a href="https://doi.org/10.1006%2Fgeno.1996.4558" target="_blank">https://doi.org/10.1006%2Fgeno.1996.4558</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: PITX1 paired-like homeodomain transcription factor 1". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5307" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5307</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: PITX1 paired-like homeodomain transcription factor 1". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5307" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5307</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Philippi A, Tores F, Carayol J, Rousseau F, Letexier M, Roschmann E, et al. (December 2007). "Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis". BMC Medical Genetics. 8: 74. doi:10.1186/1471-2350-8-74. PMC 2222245. PMID 18053270. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2222245" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2222245</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Alvarado DM, McCall K, Aferol H, Silva MJ, Garbow JR, Spees WM, et al. (October 2011). "Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice". Human Molecular Genetics. 20 (20): 3943–52. doi:10.1093/hmg/ddr313. PMC 3177645. PMID 21775501. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177645" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177645</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Klopocki E, Kähler C, Foulds N, Shah H, Joseph B, Vogel H, et al. (June 2012). "Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly". European Journal of Human Genetics. 20 (6): 705–8. doi:10.1038/ejhg.2011.264. PMC 3355260. PMID 22258522. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355260" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355260</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Spielmann M, Brancati F, Krawitz PM, Robinson PN, Ibrahim DM, Franke M, et al. (October 2012). "Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus". American Journal of Human Genetics. 91 (4): 629–35. doi:10.1016/j.ajhg.2012.08.014. PMC 3484647. PMID 23022097. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484647" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484647</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Spielmann M, Brancati F, Krawitz PM, Robinson PN, Ibrahim DM, Franke M, et al. (October 2012). "Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus". American Journal of Human Genetics. 91 (4): 629–35. doi:10.1016/j.ajhg.2012.08.014. PMC 3484647. PMID 23022097. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484647" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484647</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Alvarado DM, McCall K, Aferol H, Silva MJ, Garbow JR, Spees WM, et al. (October 2011). "Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice". Human Molecular Genetics. 20 (20): 3943–52. doi:10.1093/hmg/ddr313. PMC 3177645. PMID 21775501. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177645" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177645</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Szeto DP, Ryan AK, O'Connell SM, Rosenfeld MG (July 1996). "P-OTX: a PIT-1-interacting homeodomain factor expressed during anterior pituitary gland development". Proceedings of the National Academy of Sciences of the United States of America. 93 (15): 7706–10. Bibcode:1996PNAS...93.7706S. doi:10.1073/pnas.93.15.7706. PMC 38811. PMID 8755540. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC38811" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC38811</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> </ol>