IRGM explained

Immunity-related GTPase family M protein (IRGM), also known as interferon-inducible protein 1 (IFI1), is an enzyme that in humans is encoded by the IRGM gene.^[1]

IRGM is a member of the interferon-inducible GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens.

The gene has been disabled by an Alu element for at least 25 million years in the primate lineage leading to great apes including humans, but it was re-enabled by an endogenous retrovirus called ERV-9.^[2]

Clinical relevance

Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis.^[3]

References

Further reading

• Laukens D, Georges M, Libioulle C, Sandor C, Mni M, Vander Cruyssen B, Peeters H, Elewaut D, De Vos M . 6 . Evidence for significant overlap between common risk variants for Crohn's disease and ankylosing spondylitis . PLOS ONE . 5 . 11 . e13795 . November 2010 . 21072187 . 2970560 . 10.1371/journal.pone.0013795 . 2010PLoSO...513795L . free .
• Henckaerts L, Van Steen K, Verstreken I, Cleynen I, Franke A, Schreiber S, Rutgeerts P, Vermeire S . 6 . Genetic risk profiling and prediction of disease course in Crohn's disease patients . Clinical Gastroenterology and Hepatology . 7 . 9 . 972–980.e2 . September 2009 . 19422935 . 10.1016/j.cgh.2009.05.001 . free .
• Palomino-Morales RJ, Oliver J, Gómez-García M, López-Nevot MA, Rodrigo L, Nieto A, Alizadeh BZ, Martín J . 6 . Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach . Genes and Immunity . 10 . 4 . 356–64 . June 2009 . 19491842 . 10.1038/gene.2009.25 . 36765281 .
• Intemann CD, Thye T, Niemann S, Browne EN, Amanua Chinbuah M, Enimil A, Gyapong J, Osei I, Owusu-Dabo E, Helm S, Rüsch-Gerdes S, Horstmann RD, Meyer CG . 6 . Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains . PLOS Pathogens . 5 . 9 . e1000577 . September 2009 . 19750224 . 2735778 . 10.1371/journal.ppat.1000577 . free .
• Che N, Li S, Gao T, Zhang Z, Han Y, Zhang X, Sun Y, Liu Y, Sun Z, Zhang J, Ren W, Tian M, Li Y, Li W, Cheng J, Li C . 6 . Identification of a novel IRGM promoter single nucleotide polymorphism associated with tuberculosis . Clinica Chimica Acta; International Journal of Clinical Chemistry . 411 . 21–22 . 1645–9 . November 2010 . 20547146 . 10.1016/j.cca.2010.06.009 .
• Dema B, Fernández-Arquero M, Maluenda C, Polanco I, Figueredo MA, de la Concha EG, Urcelay E, Núñez C . 6 . Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease . Human Immunology . 70 . 11 . 946–9 . November 2009 . 19683022 . 10.1016/j.humimm.2009.08.004 .
• Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M . Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates . Genome Biology . 11 . 3 . R26 . 2010 . 20210993 . 2864566 . 10.1186/gb-2010-11-3-r26 . free .
• Wolfkamp SC, Te Velde AA, Weersma RK, Ponsioen CY, Stokkers PC . Is there a role for Crohn's disease-associated autophagy genes ATG16L1 and IRGM in formation of granulomas? . European Journal of Gastroenterology & Hepatology . 22 . 8 . 933–7 . August 2010 . 20395867 . 10.1097/MEG.0b013e32833775e6 . 20331665 .
• Singh SB, Ornatowski W, Vergne I, Naylor J, Delgado M, Roberts E, Ponpuak M, Master S, Pilli M, White E, Komatsu M, Deretic V . 6 . Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria . Nature Cell Biology . 12 . 12 . 1154–65 . December 2010 . 21102437 . 2996476 . 10.1038/ncb2119 .
• Latiano A, Palmieri O, Corritore G, Valvano MR, Bossa F, Cucchiara S, Castro M, Riegler G, De Venuto D, D'Incà R, Andriulli A, Annese V . 6 . Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease . Inflammatory Bowel Diseases . 16 . 7 . 1108–17 . July 2010 . 20024904 . 10.1002/ibd.21176 . 34309305 . 10533/126913 . free .
• Delgado M, Singh S, De Haro S, Master S, Ponpuak M, Dinkins C, Ornatowski W, Vergne I, Deretic V . 6 . Autophagy and pattern recognition receptors in innate immunity . Immunological Reviews . 227 . 1 . 189–202 . January 2009 . 19120485 . 2788953 . 10.1111/j.1600-065X.2008.00725.x .
• Törkvist L, Halfvarson J, Ong RT, Lördal M, Sjöqvist U, Bresso F, Björk J, Befrits R, Löfberg R, Blom J, Carlson M, Padyukov L, D'Amato M, Seielstad M, Pettersson S . 6 . Analysis of 39 Crohn's disease risk loci in Swedish inflammatory bowel disease patients . Inflammatory Bowel Diseases . 16 . 6 . 907–9 . June 2010 . 19760754 . 10.1002/ibd.21105 . free .
• Budarf ML, Goyette P, Boucher G, Lian J, Graham RR, Claudio JO, Hudson T, Gladman D, Clarke AE, Pope JE, Peschken C, Smith CD, Hanly J, Rich E, Boire G, Barr SG, Zummer M, Fortin PR, Wither J, Rioux JD . 6 . A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles . Genes and Immunity . 12 . 1 . 51–8 . January 2011 . 20962850 . 10.1038/gene.2010.47 . 20861744 .
• Bekpen C, Xavier RJ, Eichler EE . Human IRGM gene "to be or not to be" . Seminars in Immunopathology . 32 . 4 . 437–44 . December 2010 . 20737271 . 10.1007/s00281-010-0224-x . 39006249 .
• Cleynen I, Mahachie John JM, Henckaerts L, Van Moerkercke W, Rutgeerts P, Van Steen K, Vermeire S . Molecular reclassification of Crohn's disease by cluster analysis of genetic variants . PLOS ONE . 5 . 9 . e12952 . September 2010 . 20886065 . 2944846 . 10.1371/journal.pone.0012952 . 2010PLoSO...512952C . free .
• Wagner J, Sim WH, Ellis JA, Ong EK, Catto-Smith AG, Cameron DJ, Bishop RF, Kirkwood CD . 6 . Interaction of Crohn's disease susceptibility genes in an Australian paediatric cohort . PLOS ONE . 5 . 11 . e15376 . November 2010 . 21079743 . 2975706 . 10.1371/journal.pone.0015376 . 2010PLoSO...515376W . free .
• Meggyesi N, Kiss LS, Koszarska M, Bortlik M, Duricova D, Lakatos L, Molnar T, Leniček M, Vítek L, Altorjay I, Papp M, Tulassay Z, Miheller P, Papp J, Tordai A, Andrikovics H, Lukas M, Lakatos PL . 6 . NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients . World Journal of Gastroenterology . 16 . 41 . 5233–40 . November 2010 . 21049557 . 2975094 . 10.3748/wjg.v16.i41.5233 . free .

Notes and References

1. Web site: Entrez Gene: immunity-related GTPase family.
2. Bekpen C, Marques-Bonet T, Alkan C, Antonacci F, Leogrande MB, Ventura M, Kidd JM, Siswara P, Howard JC, Eichler EE . 6 . Death and resurrection of the human IRGM gene . PLOS Genetics . 5 . 3 . e1000403 . March 2009 . 19266026 . 2644816 . 10.1371/journal.pgen.1000403 . free .
3. Prescott NJ, Dominy KM, Kubo M, Lewis CM, Fisher SA, Redon R, Huang N, Stranger BE, Blaszczyk K, Hudspith B, Parkes G, Hosono N, Yamazaki K, Onnie CM, Forbes A, Dermitzakis ET, Nakamura Y, Mansfield JC, Sanderson J, Hurles ME, Roberts RG, Mathew CG . 6 . Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease . Human Molecular Genetics . 19 . 9 . 1828–39 . May 2010 . 20106866 . 2850616 . 10.1093/hmg/ddq041 .