PITX1 explained

Paired-like homeodomain 1 is a protein that in humans is encoded by the PITX1 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin.^[3]

Clinical relevance

Mutations in this gene have been associated with autism,^[4] club foot^[5] and polydactyly^[6] in humans.

Genetic basis of pathologies

Genomic rearrangements at the PITX1 locus are associated with Liebenberg syndrome.^[7] In PITX1 Liebenberg is associated with a translocation or deletions, which cause insert promoter groups into the PITX1 locus. A missense mutation within the PITX1 locus is associated with the development of autosomal dominant clubfoot.

Interactions

PITX1 has been shown to interact with pituitary-specific positive transcription factor 1.^[8]

Further reading

• Shang J, Luo Y, Clayton DA . Backfoot is a novel homeobox gene expressed in the mesenchyme of developing hind limb . Developmental Dynamics . 209 . 2 . 242–53 . June 1997 . 9186059 . 10.1002/(SICI)1097-0177(199706)209:2<242::AID-AJA10>3.0.CO;2-0 . 46565338 .
• Poulin G, Turgeon B, Drouin J . NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene . Molecular and Cellular Biology . 17 . 11 . 6673–82 . November 1997 . 9343431 . 232521 . 10.1128/mcb.17.11.6673 .
• Tremblay JJ, Drouin J . 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 . Molecular and Cellular Biology . 19 . 4 . 2567–76 . April 1999 . 10082522 . 84049 . 10.1128/mcb.19.4.2567 .
• Tremblay JJ, Marcil A, Gauthier Y, Drouin J . Ptx1 regulates SF-1 activity by an interaction that mimics the role of the ligand-binding domain . The EMBO Journal . 18 . 12 . 3431–41 . June 1999 . 10369682 . 1171422 . 10.1093/emboj/18.12.3431 .
• Pellegrini-Bouiller I, Manrique C, Gunz G, Grino M, Zamora AJ, Figarella-Branger D, Grisoli F, Jaquet P, Enjalbert A . Expression of the members of the Ptx family of transcription factors in human pituitary adenomas . The Journal of Clinical Endocrinology and Metabolism . 84 . 6 . 2212–20 . June 1999 . 10.1210/jcem.84.6.5760 . 10372733 . free .
• Tahara S, Kurotani R, Sanno N, Takumi I, Yoshimura S, Osamura RY, Teramoto A . Expression of pituitary homeo box 1 (Ptx1) in human non-neoplastic pituitaries and pituitary adenomas . Modern Pathology . 13 . 10 . 1097–108 . October 2000 . 11048804 . 10.1038/modpathol.3880204 . free .
• Quentien MH, Manfroid I, Moncet D, Gunz G, Muller M, Grino M, Enjalbert A, Pellegrini I . Pitx factors are involved in basal and hormone-regulated activity of the human prolactin promoter . The Journal of Biological Chemistry . 277 . 46 . 44408–16 . November 2002 . 12223489 . 10.1074/jbc.M207824200 . free .
• Ghosh AK, Majumder M, Steele R, Ray R, Ray RB . Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1 . Virology . 306 . 1 . 51–9 . February 2003 . 12620797 . 10.1016/S0042-6822(02)00029-6 . free .
• Hiroi N, Kino T, Bassett M, Rainey WE, Phung M, Abu-Asab M, Fojo T, Briata P, Chrousos GP, Bornstein SR . Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase . Hormone and Metabolic Research . 35 . 5 . 273–8 . May 2003 . 12915995 . 10.1055/s-2003-41301 . 260168691 .
• Kolfschoten IG, van Leeuwen B, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Voorhoeve PM, Agami R . A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity . Cell . 121 . 6 . 849–58 . June 2005 . 15960973 . 10.1016/j.cell.2005.04.017 . 1874/17813 . 18065721 . free .
• Lord RV, Brabender J, Wickramasinghe K, DeMeester SR, Holscher A, Schneider PM, Danenberg PV, DeMeester TR . Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma . Surgery . 138 . 5 . 924–31 . November 2005 . 16291394 . 10.1016/j.surg.2005.05.007 .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Picard C, Azeddine B, Moldovan F, Martel-Pelletier J, Moreau A . New emerging role of pitx1 transcription factor in osteoarthritis pathogenesis . Clinical Orthopaedics and Related Research . 462 . 59–66 . September 2007 . 17549029 . 10.1097/BLO.0b013e3180d09d9c . 8232057 .
• Qi DL, Ohhira T, Fujisaki C, Inoue T, Ohta T, Osaki M, Ohshiro E, Seko T, Aoki S, Oshimura M, Kugoh H . Identification of PITX1 as a TERT suppressor gene located on human chromosome 5 . Molecular and Cellular Biology . 31 . 8 . 1624–36 . April 2011 . 21300782 . 3126332 . 10.1128/MCB.00470-10 .

External links

• • • • http://omim.org/entry/602149 at OMIM, holds the most up to date information on PITX1.
  • https://ghr.nlm.nih.gov/gene/PITX1 at the NIH, has a summary on the effects of PITX1 mutations.

Notes and References

1. Crawford MJ, Lanctôt C, Tremblay JJ, Jenkins N, Gilbert D, Copeland N, Beatty B, Drouin J . Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome . Mammalian Genome . 8 . 11 . 841–5 . 1997 . 9337397 . 10.1007/s003359900589 . 10.1.1.326.9619 . 8557603 .
2. Shang J, Li X, Ring HZ, Clayton DA, Francke U . Backfoot, a novel homeobox gene, maps to human chromosome 5 (BFT) and mouse chromosome 13 (Bft) . Genomics . 40 . 1 . 108–13 . February 1997 . 9070926 . 10.1006/geno.1996.4558 . free .
3. Web site: Entrez Gene: PITX1 paired-like homeodomain transcription factor 1.
4. Philippi A, Tores F, Carayol J, Rousseau F, Letexier M, Roschmann E, Lindenbaum P, Benajjou A, Fontaine K, Vazart C, Gesnouin P, Brooks P, Hager J . 6 . 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 . December 2007 . 18053270 . 2222245 . 10.1186/1471-2350-8-74 . free .
5. Alvarado DM, McCall K, Aferol H, Silva MJ, Garbow JR, Spees WM, Patel T, Siegel M, Dobbs MB, Gurnett CA . 6 . Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice . Human Molecular Genetics . 20 . 20 . 3943–52 . October 2011 . 21775501 . 3177645 . 10.1093/hmg/ddr313 .
6. Klopocki E, Kähler C, Foulds N, Shah H, Joseph B, Vogel H, Lüttgen S, Bald R, Besoke R, Held K, Mundlos S, Kurth I . 6 . Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly . European Journal of Human Genetics . 20 . 6 . 705–8 . June 2012 . 22258522 . 3355260 . 10.1038/ejhg.2011.264 .
7. Spielmann M, Brancati F, Krawitz PM, Robinson PN, Ibrahim DM, Franke M, Hecht J, Lohan S, Dathe K, Nardone AM, Ferrari P, Landi A, Wittler L, Timmermann B, Chan D, Mennen U, Klopocki E, Mundlos S . 6 . Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus . American Journal of Human Genetics . 91 . 4 . 629–35 . October 2012 . 23022097 . 3484647 . 10.1016/j.ajhg.2012.08.014 .
8. Szeto DP, Ryan AK, O'Connell SM, Rosenfeld MG . 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 . July 1996 . 8755540 . 38811 . 10.1073/pnas.93.15.7706 . 1996PNAS...93.7706S . free .