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IRX3 is a member of the [[Iroquois homeobox factor|Iroquois homeobox]] gene family and plays a role in an early step of neural development.<ref name="pmid9427753">{{cite journal | vauthors = Bellefroid EJ, Kobbe A, Gruss P, Pieler T, Gurdon JB, Papalopulu N | title = Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification | journal = The EMBO Journal | volume = 17 | issue = 1 | pages = 191–203 | date = Jan 1998 | pmid = 9427753 | pmc = 1170370 | doi = 10.1093/emboj/17.1.191 }}</ref> Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.<ref name="entrez"/><ref name="pmid10370142">{{cite journal | vauthors = Lewis MT, Ross S, Strickland PA, Snyder CJ, Daniel CW | title = Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast | journal = Cell and Tissue Research | volume = 296 | issue = 3 | pages = 549–54 | date = Jun 1999 | pmid = 10370142 | doi = 10.1007/s004410051316 }}</ref>
IRX3 is a member of the [[Iroquois homeobox factor|Iroquois homeobox]] gene family and plays a role in an early step of neural development.<ref name="pmid9427753">{{cite journal | vauthors = Bellefroid EJ, Kobbe A, Gruss P, Pieler T, Gurdon JB, Papalopulu N | title = Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification | journal = The EMBO Journal | volume = 17 | issue = 1 | pages = 191–203 | date = Jan 1998 | pmid = 9427753 | pmc = 1170370 | doi = 10.1093/emboj/17.1.191 }}</ref> Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.<ref name="entrez"/><ref name="pmid10370142">{{cite journal | vauthors = Lewis MT, Ross S, Strickland PA, Snyder CJ, Daniel CW | title = Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast | journal = Cell and Tissue Research | volume = 296 | issue = 3 | pages = 549–54 | date = Jun 1999 | pmid = 10370142 | doi = 10.1007/s004410051316 }}</ref>
Specifically, IRX3 contributes to pattern formation in the spinal cord where it tranlates a [[morphogen]] gradient into transcriptional events, and is directly regulated by [[NKX2-2]].<ref name="pmid25398016">{{cite journal | vauthors = Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, Dinnyés A, Kovács KA | title = Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord | journal = PloS One | volume = 9 | issue = 11 | pages = e111430 | date = November 2014 | pmid = 25398016 | doi = 10.1371/journal.pone.0111430 | url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111430 }}</ref>
Specifically, IRX3 contributes to pattern formation in the spinal cord where it tranlates a [[morphogen]] gradient into transcriptional events, and is directly regulated by [[NKX2-2]].<ref name="pmid25398016">{{cite journal | vauthors = Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, Dinnyés A, Kovács KA | title = Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord | journal = PloS One | volume = 9 | issue = 11 | pages = e111430 | date = November 2014 | pmid = 25398016 | doi = 10.1371/journal.pone.0111430 }}</ref>


==Clinical significance==
==Clinical significance==
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===Association with obesity===
===Association with obesity===


Obesity-associated noncoding sequences within FTO interact with the promoter of IRX3 and FTO in human, mouse, and zebrafish. Obesity-associated [[single nucleotide polymorphisms]] are related to the expression of IRX3 (not FTO) in the human brain. A direct connection between the expression of IRX3 and body mass and composition was shown through the decrease in body weight of 25-30% in IRX3-deficient mice. This suggests that IRX3 influences obesity.<ref>{{cite journal | vauthors = Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA | title = Obesity-associated variants within FTO form long-range functional connections with IRX3 | journal = Nature | volume = 507 | issue = 7492 | pages = 371–5 | date = Mar 2014 | pmid = 24646999 | doi = 10.1038/nature13138 }}</ref> Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.<ref>{{cite journal |vauthors = Claussnitzer M, Dankel S, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J,Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M|title = FTO Obesity Variant Circuitry and Adipocyte Browning in Humans|date = Aug 2015|pmid = 26287746|doi = 10.1056/NEJMoa1502214|journal = [[N. Engl. J. Med.|New England Journal of Medicine]]|lay-url = http://www.bizjournals.com/boston/blog/health-care/2015/08/mit-harvard-find-master-switch-behind-obesity.html|lay-date = 20 Aug 2015|lay-source = [[Boston Bus. J.|Boston Business Journal]]|volume=373 |pages=895–907}}{{Open access}}</ref>
Obesity-associated noncoding sequences within FTO interact with the promoter of IRX3 and FTO in human, mouse, and zebrafish. Obesity-associated [[single nucleotide polymorphisms]] are related to the expression of IRX3 (not FTO) in the human brain. A direct connection between the expression of IRX3 and body mass and composition was shown through the decrease in body weight of 25-30% in IRX3-deficient mice. This suggests that IRX3 influences obesity.<ref>{{cite journal | vauthors = Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA | title = Obesity-associated variants within FTO form long-range functional connections with IRX3 | journal = Nature | volume = 507 | issue = 7492 | pages = 371–5 | date = Mar 2014 | pmid = 24646999 | doi = 10.1038/nature13138 }}</ref> Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.<ref>{{cite journal | vauthors = Claussnitzer M, Dankel S, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J,Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M | title = FTO Obesity Variant Circuitry and Adipocyte Browning in Humans | date = Aug 2015 | pmid = 26287746 | doi = 10.1056/NEJMoa1502214|journal = [[N. Engl. J. Med.|New England Journal of Medicine]]|lay-url = http://www.bizjournals.com/boston/blog/health-care/2015/08/mit-harvard-find-master-switch-behind-obesity.htm l |lay-date = 20 Aug 2015 | lay-source = [[Boston Bus. J.|Boston Business Journal]] | volume = 373 | pages = 895–907 }}{{Open access}}</ref>
It is worth pointing that recently genetic variants of FTO and IRX3 genes are reported in high LD and are associated with obesity risk in North Indians, signifying them as important genetic determinants of obesity risk in humans [7].
Genetic variants of FTO and IRX3 genes are in high [[linkage disequilibrium]] and are associated with obesity risk.<ref name="pmid26440677">{{cite journal | vauthors = Srivastava A, Mittal B, Prakash J, Srivastava P, Srivastava N, Srivastava N | title = Association of FTO and IRX3 genetic variants to obesity risk in north India | journal = Annals of Human Biology | volume = | issue = | pages = 1–6 | year = 2015 | pmid = 26440677 | doi = 10.3109/03014460.2015.1103902 }}</ref>


== References ==
== References ==
{{reflist|33em}}
{{reflist|33em}}
7. Apurva Srivastava, Balraj Mittal, Jai Prakash, Pranjal Srivastava, Nimisha Srivastava & Neena Srivastava. Association of FTO and IRX3 genetic variants to obesity risk in North India. Ann Hum Biol. 2015. Early Online: 1–6.


== Further reading ==
== Further reading ==

Revision as of 10:50, 28 December 2015

Template:PBB Iroquois-class homeodomain protein IRX-3, also known as Iroquois homeobox protein 3, is a protein that in humans is encoded by the IRX3 gene.[1]

Function

IRX3 is a member of the Iroquois homeobox gene family and plays a role in an early step of neural development.[2] Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.[1][3] Specifically, IRX3 contributes to pattern formation in the spinal cord where it tranlates a morphogen gradient into transcriptional events, and is directly regulated by NKX2-2.[4]

Clinical significance

Association with obesity

Obesity-associated noncoding sequences within FTO interact with the promoter of IRX3 and FTO in human, mouse, and zebrafish. Obesity-associated single nucleotide polymorphisms are related to the expression of IRX3 (not FTO) in the human brain. A direct connection between the expression of IRX3 and body mass and composition was shown through the decrease in body weight of 25-30% in IRX3-deficient mice. This suggests that IRX3 influences obesity.[5] Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.[6] Genetic variants of FTO and IRX3 genes are in high linkage disequilibrium and are associated with obesity risk.[7]

References

  1. ^ a b "Entrez Gene: iroquois homeobox 3".
  2. ^ Bellefroid EJ, Kobbe A, Gruss P, Pieler T, Gurdon JB, Papalopulu N (Jan 1998). "Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification". The EMBO Journal. 17 (1): 191–203. doi:10.1093/emboj/17.1.191. PMC 1170370. PMID 9427753.
  3. ^ Lewis MT, Ross S, Strickland PA, Snyder CJ, Daniel CW (Jun 1999). "Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast". Cell and Tissue Research. 296 (3): 549–54. doi:10.1007/s004410051316. PMID 10370142.
  4. ^ Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, Dinnyés A, Kovács KA (November 2014). "Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord". PloS One. 9 (11): e111430. doi:10.1371/journal.pone.0111430. PMID 25398016.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA (Mar 2014). "Obesity-associated variants within FTO form long-range functional connections with IRX3". Nature. 507 (7492): 371–5. doi:10.1038/nature13138. PMID 24646999.
  6. ^ Claussnitzer M, Dankel S, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M (Aug 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". New England Journal of Medicine. 373: 895–907. doi:10.1056/NEJMoa1502214. PMID 26287746. {{cite journal}}: Unknown parameter |lay-date= ignored (help); Unknown parameter |lay-source= ignored (help); Unknown parameter |lay-url= ignored (help)Open access icon
  7. ^ Srivastava A, Mittal B, Prakash J, Srivastava P, Srivastava N, Srivastava N (2015). "Association of FTO and IRX3 genetic variants to obesity risk in north India". Annals of Human Biology: 1–6. doi:10.3109/03014460.2015.1103902. PMID 26440677.

Further reading

  • Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, de Kovel C, Holmes GK, Howdle PD, Walters JR, Sanders DS, Mulder CJ, Mearin ML, Verbeek WH, Trimble V, Stevens FM, Kelleher D, Barisani D, Bardella MT, McManus R, van Heel DA, Wijmenga C (Aug 2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–83. doi:10.1136/gut.2008.169052. PMID 19240061.
  • Ragvin A, Moro E, Fredman D, Navratilova P, Drivenes Ø, Engström PG, Alonso ME, de la Calle Mustienes E, Gómez Skarmeta JL, Tavares MJ, Casares F, Manzanares M, van Heyningen V, Molven A, Njølstad PR, Argenton F, Lenhard B, Becker TS (Jan 2010). "Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3". Proceedings of the National Academy of Sciences of the United States of America. 107 (2): 775–80. doi:10.1073/pnas.0911591107. PMC 2818943. PMID 20080751.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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