Interleukin-23 receptor: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''Interleukin 23 receptor''' is a [[type I cytokine receptor]]. '''IL23R''' is its human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: IL23R interleukin 23 receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=149233| accessdate = }}</ref>
'''Interleukin-23 receptor''' is a [[type I cytokine receptor]]. '''''IL23R''''' is the name of its human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: IL23R interleukin 23 receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=149233| accessdate = }}</ref>


== Function ==
== Function ==


The protein encoded by this gene is a subunit of the receptor for [[IL23A]]/IL23. This protein pairs with the receptor molecule [[IL12RB1]]/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 ([[JAK2]]), and also binds to transcription activator [[STAT3]] in a ligand-dependent manner.<ref name="entrez"/>
The protein encoded by this gene is a subunit of the receptor for [[Interleukin 23|IL-23]]. This protein pairs with the receptor molecule IL-12Rβ1 ([[IL12RB1]]), together forming the IL-23 receptor complex,  and both are required for IL-23 signaling. This protein associates constitutively with Janus kinase 2 ([[JAK2]]), and also binds to transcription activator [[STAT3]] in a ligand-dependent manner.<ref name="entrez"/>


==Clinical significance==
==Clinical significance==


Three variants in the IL23R gene have been shown to protect against [[Crohn's disease]] and [[ulcerative colitis]].<ref>{{cite journal | vauthors = Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH | title = A genome-wide association study identifies IL23R as an inflammatory bowel disease gene | journal = Science | volume = 314 | issue = 5804 | pages = 1461–3 | date = Dec 2006 | pmid = 17068223 | doi = 10.1126/science.1135245 | display-authors = 6 }}</ref><ref>{{cite journal | vauthors = Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, Boucher G, Ripke S, Ellinghaus D, Burtt N, Fennell T, Kirby A, Latiano A, Goyette P, Green T, Halfvarson J, Haritunians T, Korn JM, Kuruvilla F, Lagacé C, Neale B, Lo KS, Schumm P, Törkvist L, Dubinsky MC, Brant SR, Silverberg MS, Duerr RH, Altshuler D, Gabriel S, Lettre G, Franke A, D'Amato M, McGovern DP, Cho JH, Rioux JD, Xavier RJ, Daly MJ | title = Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease | journal = Nature Genetics | volume = 43 | issue = 11 | pages = 1066–73 | date = Nov 2011 | pmid = 21983784 | doi = 10.1038/ng.952 | display-authors = 6 | pmc=3378381}}</ref><ref>{{cite journal | vauthors = Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, Cleynen I, Colombel JF, de Rijk P, Dewit O, Finkel Y, Gassull MA, Goossens D, Laukens D, Lémann M, Libioulle C, O'Morain C, Reenaers C, Rutgeerts P, Tysk C, Zelenika D, Lathrop M, Del-Favero J, Hugot JP, de Vos M, Franchimont D, Vermeire S, Louis E, Georges M | title = Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease | journal = Nature Genetics | volume = 43 | issue = 1 | pages = 43–7 | date = Jan 2011 | pmid = 21151126 | doi = 10.1038/ng.733 | display-authors = 6 }}</ref>
Three variants in the ''IL23R'' gene have been shown to protect against [[Crohn's disease]] and [[ulcerative colitis]].<ref>{{cite journal | vauthors = Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH | title = A genome-wide association study identifies IL23R as an inflammatory bowel disease gene | journal = Science | volume = 314 | issue = 5804 | pages = 1461–3 | date = Dec 2006 | pmid = 17068223 | doi = 10.1126/science.1135245 | display-authors = 6 | pmc = 4410764 }}</ref><ref>{{cite journal | vauthors = Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, Boucher G, Ripke S, Ellinghaus D, Burtt N, Fennell T, Kirby A, Latiano A, Goyette P, Green T, Halfvarson J, Haritunians T, Korn JM, Kuruvilla F, Lagacé C, Neale B, Lo KS, Schumm P, Törkvist L, Dubinsky MC, Brant SR, Silverberg MS, Duerr RH, Altshuler D, Gabriel S, Lettre G, Franke A, D'Amato M, McGovern DP, Cho JH, Rioux JD, Xavier RJ, Daly MJ | title = Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease | journal = Nature Genetics | volume = 43 | issue = 11 | pages = 1066–73 | date = Nov 2011 | pmid = 21983784 | doi = 10.1038/ng.952 | display-authors = 6 | pmc=3378381}}</ref><ref>{{cite journal | vauthors = Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, Cleynen I, Colombel JF, de Rijk P, Dewit O, Finkel Y, Gassull MA, Goossens D, Laukens D, Lémann M, Libioulle C, O'Morain C, Reenaers C, Rutgeerts P, Tysk C, Zelenika D, Lathrop M, Del-Favero J, Hugot JP, de Vos M, Franchimont D, Vermeire S, Louis E, Georges M | title = Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease | journal = Nature Genetics | volume = 43 | issue = 1 | pages = 43–7 | date = Jan 2011 | pmid = 21151126 | doi = 10.1038/ng.733 | display-authors = 6 }}</ref>
The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.<ref name="pmid18675459">{{cite journal | vauthors = de Paus RA, van de Wetering D, van Dissel JT, van de Vosse E | title = IL-23 and IL-12 responses in activated human T cells retrovirally transduced with IL-23 receptor variants | journal = Molecular Immunology | volume = 45 | issue = 15 | pages = 3889–95 | date = September 2008 | pmid = 18675459 | doi = 10.1016/j.molimm.2008.06.029 | url = }}</ref>


==Model organisms==
==Model organisms==
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* {{cite journal | vauthors = Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW | title = A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R | journal = Journal of Immunology | volume = 168 | issue = 11 | pages = 5699–708 | date = Jun 2002 | pmid = 12023369 | doi = 10.4049/jimmunol.168.11.5699 }}
* {{cite journal | vauthors = Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW | title = A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R | journal = Journal of Immunology | volume = 168 | issue = 11 | pages = 5699–708 | date = Jun 2002 | pmid = 12023369 | doi = 10.4049/jimmunol.168.11.5699 }}
* {{cite journal | vauthors = Zhang XY, Zhang HJ, Zhang Y, Fu YJ, He J, Zhu LP, Wang SH, Liu L | title = Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells | journal = Immunogenetics | volume = 57 | issue = 12 | pages = 934–43 | date = Jan 2006 | pmid = 16372191 | doi = 10.1007/s00251-005-0067-0 }}
* {{cite journal | vauthors = Zhang XY, Zhang HJ, Zhang Y, Fu YJ, He J, Zhu LP, Wang SH, Liu L | title = Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells | journal = Immunogenetics | volume = 57 | issue = 12 | pages = 934–43 | date = Jan 2006 | pmid = 16372191 | doi = 10.1007/s00251-005-0067-0 }}
* {{cite journal | vauthors = Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH | title = A genome-wide association study identifies IL23R as an inflammatory bowel disease gene | journal = Science | volume = 314 | issue = 5804 | pages = 1461–3 | date = Dec 2006 | pmid = 17068223 | doi = 10.1126/science.1135245 }}
* {{cite journal | vauthors = Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH | title = A genome-wide association study identifies IL23R as an inflammatory bowel disease gene | journal = Science | volume = 314 | issue = 5804 | pages = 1461–3 | date = Dec 2006 | pmid = 17068223 | doi = 10.1126/science.1135245 | pmc = 4410764 }}
* {{cite journal | vauthors = Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB | title = A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes | journal = American Journal of Human Genetics | volume = 80 | issue = 2 | pages = 273–90 | date = Feb 2007 | pmid = 17236132 | pmc = 1785338 | doi = 10.1086/511051 }}
* {{cite journal | vauthors = Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB | title = A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes | journal = American Journal of Human Genetics | volume = 80 | issue = 2 | pages = 273–90 | date = Feb 2007 | pmid = 17236132 | pmc = 1785338 | doi = 10.1086/511051 }}
* {{cite journal | vauthors = Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, Dutridge D, Wahbeh G, Silber G, Bahar R, Mengesha E, Targan SR, Taylor KD, Rotter JI | title = IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease | journal = Inflammatory Bowel Diseases | volume = 13 | issue = 5 | pages = 511–5 | date = May 2007 | pmid = 17309073 | pmc = 2169293 | doi = 10.1002/ibd.20126 }}
* {{cite journal | vauthors = Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, Dutridge D, Wahbeh G, Silber G, Bahar R, Mengesha E, Targan SR, Taylor KD, Rotter JI | title = IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease | journal = Inflammatory Bowel Diseases | volume = 13 | issue = 5 | pages = 511–5 | date = May 2007 | pmid = 17309073 | pmc = 2169293 | doi = 10.1002/ibd.20126 }}
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* {{cite journal | vauthors = Cummings JR, Ahmad T, Geremia A, Beckly J, Cooney R, Hancock L, Pathan S, Guo C, Cardon LR, Jewell DP | title = Contribution of the novel inflammatory bowel disease gene IL23R to disease susceptibility and phenotype | journal = Inflammatory Bowel Diseases | volume = 13 | issue = 9 | pages = 1063–8 | date = Sep 2007 | pmid = 17508420 | doi = 10.1002/ibd.20180 }}
* {{cite journal | vauthors = Cummings JR, Ahmad T, Geremia A, Beckly J, Cooney R, Hancock L, Pathan S, Guo C, Cardon LR, Jewell DP | title = Contribution of the novel inflammatory bowel disease gene IL23R to disease susceptibility and phenotype | journal = Inflammatory Bowel Diseases | volume = 13 | issue = 9 | pages = 1063–8 | date = Sep 2007 | pmid = 17508420 | doi = 10.1002/ibd.20180 }}
* {{cite journal | vauthors = Yamazaki K, Onouchi Y, Takazoe M, Kubo M, Nakamura Y, Hata A | title = Association analysis of genetic variants in IL23R, ATG16L1 and 5p13.1 loci with Crohn's disease in Japanese patients | journal = Journal of Human Genetics | volume = 52 | issue = 7 | pages = 575–83 | year = 2007 | pmid = 17534574 | doi = 10.1007/s10038-007-0156-z }}
* {{cite journal | vauthors = Yamazaki K, Onouchi Y, Takazoe M, Kubo M, Nakamura Y, Hata A | title = Association analysis of genetic variants in IL23R, ATG16L1 and 5p13.1 loci with Crohn's disease in Japanese patients | journal = Journal of Human Genetics | volume = 52 | issue = 7 | pages = 575–83 | year = 2007 | pmid = 17534574 | doi = 10.1007/s10038-007-0156-z }}
* {{cite journal | vauthors = Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, Frackelton EC, Otieno FG, Kanterakis S, Shaner JL, Smith RM, Eckert AW, Robinson LJ, Onyiah CC, Abrams DJ, Chiavacci RM, Skraban R, Devoto M, Grant SF, Hakonarson H | title = Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease | journal = Clinical Gastroenterology and Hepatology | volume = 5 | issue = 8 | pages = 972–6 | date = Aug 2007 | pmid = 17618837 | doi = 10.1016/j.cgh.2007.04.024 }}
* {{cite journal | vauthors = Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, Frackelton EC, Otieno FG, Kanterakis S, Shaner JL, Smith RM, Eckert AW, Robinson LJ, Onyiah CC, Abrams DJ, Chiavacci RM, Skraban R, Devoto M, Grant SF, Hakonarson H | title = Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease | journal = Clinical Gastroenterology and Hepatology | volume = 5 | issue = 8 | pages = 972–6 | date = Aug 2007 | pmid = 17618837 | doi = 10.1016/j.cgh.2007.04.024 | pmc = 4287202 }}
* {{cite journal | vauthors = Sánchez E, Rueda B, Callejas JL, Sabio JM, Ortego-Centeno N, Jimenez-Alonso J, López-Nevot MA, Martín J | title = Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus | journal = Tissue Antigens | volume = 70 | issue = 3 | pages = 233–7 | date = Sep 2007 | pmid = 17661912 | doi = 10.1111/j.1399-0039.2007.00881.x }}
* {{cite journal | vauthors = Sánchez E, Rueda B, Callejas JL, Sabio JM, Ortego-Centeno N, Jimenez-Alonso J, López-Nevot MA, Martín J | title = Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus | journal = Tissue Antigens | volume = 70 | issue = 3 | pages = 233–7 | date = Sep 2007 | pmid = 17661912 | doi = 10.1111/j.1399-0039.2007.00881.x }}
* {{cite journal | vauthors = Orozco G, Rueda B, Robledo G, García A, Martín J | title = Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort | journal = Human Immunology | volume = 68 | issue = 8 | pages = 681–4 | date = Aug 2007 | pmid = 17678723 | doi = 10.1016/j.humimm.2007.05.008 }}
* {{cite journal | vauthors = Orozco G, Rueda B, Robledo G, García A, Martín J | title = Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort | journal = Human Immunology | volume = 68 | issue = 8 | pages = 681–4 | date = Aug 2007 | pmid = 17678723 | doi = 10.1016/j.humimm.2007.05.008 }}

Latest revision as of 12:47, 5 June 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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n/a

RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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View/Edit Human

Interleukin-23 receptor is a type I cytokine receptor. IL23R is the name of its human gene.[1]

Function

The protein encoded by this gene is a subunit of the receptor for IL-23. This protein pairs with the receptor molecule IL-12Rβ1 (IL12RB1), together forming the IL-23 receptor complex, and both are required for IL-23 signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner.[1]

Clinical significance

Three variants in the IL23R gene have been shown to protect against Crohn's disease and ulcerative colitis.[2][3][4] The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.[5]

Model organisms

Model organisms have been used in the study of IL23R function. A conditional knockout mouse line called Il23rtm2a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12]

References

  1. 1.0 1.1 "Entrez Gene: IL23R interleukin 23 receptor".
  2. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. (Dec 2006). "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene". Science. 314 (5804): 1461–3. doi:10.1126/science.1135245. PMC 4410764. PMID 17068223.
  3. Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, et al. (Nov 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease". Nature Genetics. 43 (11): 1066–73. doi:10.1038/ng.952. PMC 3378381. PMID 21983784.
  4. Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, et al. (Jan 2011). "Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease". Nature Genetics. 43 (1): 43–7. doi:10.1038/ng.733. PMID 21151126.
  5. de Paus RA, van de Wetering D, van Dissel JT, van de Vosse E (September 2008). "IL-23 and IL-12 responses in activated human T cells retrovirally transduced with IL-23 receptor variants". Molecular Immunology. 45 (15): 3889–95. doi:10.1016/j.molimm.2008.06.029. PMID 18675459.
  6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  7. 7.0 7.1 "International Mouse Phenotyping Consortium".
  8. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  9. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  10. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  11. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  12. 12.0 12.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading