NOD2

Summary

Gene Symbol: NOD2
Description: nucleotide binding oligomerization domain containing 2
Alias: ACUG, BLAU, BLAUS, CARD15, CLR16.3, IBD1, NLRC2, NOD2B, PSORAS1, YAOS, nucleotide-binding oligomerization domain-containing protein 2, NLR family, CARD domain containing 2, NOD-like receptor C2, caspase recruitment domain family, member 15, caspase recruitment domain protein 15, caspase recruitment domain-containing protein 15, inflammatory bowel disease protein 1, nucleotide-binding oligomerization domain 2, nucleotide-binding oligomerization domain, leucine rich repeat and CARD domain containing 2
Species: human
Products:     NOD2

Top Publications

  1. Milman N, Nielsen F, Hviid T, Hansen T. Blau syndrome-associated mutations in exon 4 of the caspase activating recruitment domain 15 (CARD 15) gene are not found in ethnic Danes with sarcoidosis. Clin Respir J. 2007;1:74-9 pubmed publisher
    Distinct mutations of the caspase activating recruitment domain 15 (CARD15) gene (also known as nucleotide-binding oligomerisation domain protein 2) on chromosome 16q are associated with the chronic granulomatous disease called Blau ..
  2. Noguchi E, Homma Y, Kang X, Netea M, Ma X. A Crohn's disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1. Nat Immunol. 2009;10:471-9 pubmed publisher
    A common mutation in the gene encoding the cytoplasmic sensor Nod2, involving a frameshift insertion at nucleotide 3020 (3020insC), is strongly associated with Crohn's disease...
  3. Zurek B, Proell M, Wagner R, Schwarzenbacher R, Kufer T. Mutational analysis of human NOD1 and NOD2 NACHT domains reveals different modes of activation. Innate Immun. 2012;18:100-11 pubmed publisher
    ..affecting key residues of the ATPase domain of NOD2 are linked to severe auto-inflammatory diseases, such as Blau syndrome and early-onset sarcoidosis...
  4. Weersma R, Stokkers P, van Bodegraven A, Van Hogezand R, Verspaget H, de Jong D, et al. Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort. Gut. 2009;58:388-95 pubmed publisher
    ..association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) ..
  5. van Eijk M, Scheij S, van Roomen C, Speijer D, Boot R, Aerts J. TLR- and NOD2-dependent regulation of human phagocyte-specific chitotriosidase. FEBS Lett. 2007;581:5389-95 pubmed
    ..We find that TLR, but not NOD2 activation, regulates chitotriosidase release by neutrophils...
  6. LeBlanc P, Yeretssian G, Rutherford N, Doiron K, Nadiri A, Zhu L, et al. Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity. Cell Host Microbe. 2008;3:146-57 pubmed publisher
    ..Nod1 and Nod2 associate with the kinase Rip2 to stimulate NF-kappaB signaling...
  7. Tanabe T, Yamaguchi N, Matsuda K, Yamazaki K, Takahashi S, Tojo A, et al. Association analysis of the NOD2 gene with susceptibility to graft-versus-host disease in a Japanese population. Int J Hematol. 2011;93:771-778 pubmed publisher
    ..Recent studies in Caucasians revealed the association between mutants of NOD2, a member of the NLR family, and severity of acute graft-versus-host disease (GVHD)...
  8. Okafuji I, Nishikomori R, Kanazawa N, Kambe N, Fujisawa A, Yamazaki S, et al. Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis. Arthritis Rheum. 2009;60:242-50 pubmed publisher
    b>Blau syndrome and its sporadic counterpart, early-onset sarcoidosis (EOS), share a phenotype featuring the symptom triad of skin rash, arthritis, and uveitis...
  9. Ennas M, Moore P, Zucca M, Angelucci E, Cabras M, Melis M, et al. Interleukin-1B (IL1B) and interleukin-6 (IL6) gene polymorphisms are associated with risk of chronic lymphocytic leukaemia. Hematol Oncol. 2008;26:98-103 pubmed publisher
    ..C, IL6-597G > A, IL10-1082A > G, IL10-3575T > A, TNF-308G > A, LTA- 91A > C, LTA 252A > G and CARD15 nt1007...

More Information

Publications96

  1. Austin C, Ma X, Graviss E. Common nonsynonymous polymorphisms in the NOD2 gene are associated with resistance or susceptibility to tuberculosis disease in African Americans. J Infect Dis. 2008;197:1713-6 pubmed publisher
    Pattern-recognition receptors (PRRs) play a key role in innate immunity against intracellular bacteria. NOD2 is one of the PRRs that contribute to the immune response to Mycobacterium tuberculosis infection...
  2. Milman N, Ursin K, Rødevand E, Nielsen F, Hansen T. A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian family with four affected members. Scand J Rheumatol. 2009;38:190-7 pubmed publisher
    ..It is caused by mutations in the NOD2 gene, also termed the CARD15 gene. To report a novel mutation in the NOD2 gene associated with Blau syndrome...
  3. Guerra J, Zasloff M, Lough D, Abdo J, Hawksworth J, Mastumoto C, et al. Nucleotide oligomerization domain 2 polymorphisms in patients with intestinal failure. J Gastroenterol Hepatol. 2013;28:309-13 pubmed publisher
    Nucleotide oligomerization domain 2 (NOD2) has been associated with intestinal immunity after the discovery that its polymorphisms are linked to Crohn's disease (CD)...
  4. Weiss B, Lebowitz O, Fidder H, Maza I, Levine A, Shaoul R, et al. Response to medical treatment in patients with Crohn's disease: the role of NOD2/CRAD15, disease phenotype, and age of diagnosis. Dig Dis Sci. 2010;55:1674-80 pubmed publisher
    ..We aimed to evaluate the relationships between NOD2/CARD15 mutations, disease phenotype and age of CD diagnosis and response to medical treatment with systemic steroids, ..
  5. Franchi L, Warner N, Viani K, Nunez G. Function of Nod-like receptors in microbial recognition and host defense. Immunol Rev. 2009;227:106-28 pubmed publisher
    ..In this review, we focus on the role of Nod1 and Nod2 in host defense and in particular discuss recent finding regarding the role of Nlrc4, Nlpr1, and Nlrp3 ..
  6. Appenrodt B, Grunhage F, Gentemann M, Thyssen L, Sauerbruch T, Lammert F. Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis. Hepatology. 2010;51:1327-33 pubmed publisher
    ..Variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene have been associated with impaired mucosal barrier ..
  7. Roberts R, Gearry R, Hollis Moffatt J, Miller A, Reid J, Abkevich V, et al. IL23R R381Q and ATG16L1 T300A are strongly associated with Crohn's disease in a study of New Zealand Caucasians with inflammatory bowel disease. Am J Gastroenterol. 2007;102:2754-61 pubmed
    ..rs11209026 and rs2241880 genotype distributions were examined both within IBD clinical subphenotypes and CARD15 genotypes. rs11209026 and rs2241880 were both associated with CD (P valuers11209026=0.0026, OR 0.54, 95% CI 0.36-0...
  8. Brooks M, Rajaram M, Azad A, Amer A, Valdivia Arenas M, Park J, et al. NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages. Cell Microbiol. 2011;13:402-18 pubmed publisher
    ..b>NOD2-mediated signalling pathways in response to M...
  9. Rose C, Arostegui J, Martin T, Espada G, Scalzi L, Yague J, et al. NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain. Arthritis Rheum. 2009;60:1797-803 pubmed publisher
    ..the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene...
  10. Rigoli L, Di Bella C, Fedele F, Procopio V, Amorini M, Lo Giudice G, et al. TLR4 and NOD2/CARD15 genetic polymorphisms and their possible role in gastric carcinogenesis. Anticancer Res. 2010;30:513-7 pubmed
    The aim of this study was to evaluate the role of TLR4 and NOD2/CARD15 genes in gastric carcinogenesis...
  11. Homer C, Richmond A, Rebert N, Achkar J, McDonald C. ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn's disease pathogenesis. Gastroenterology. 2010;139:1630-41, 1641.e1-2 pubmed publisher
    ..We examined the functional interaction between the CD risk genes ATG16L1 and NOD2 to identify an autophagy-dependent pathway that is altered by disease-associated variants...
  12. Elmaagacli A, Steckel N, Ditschkowski M, Hegerfeldt Y, Ottinger H, Trenschel R, et al. Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors. Bone Marrow Transplant. 2011;46:702-8 pubmed publisher
    We evaluated the influence of gene polymorphisms of TLR9 (T1237C; T1486C), IL23R (A1142G), and NOD2 SNP8 (R702W), SNP12 (G908R) and SNP13 (1007fs) on outcome of hematopoietic SCT in a homogenous group of 142 AML patients after non-T-cell-..
  13. Lee K, Biswas A, Liu Y, Kobayashi K. Proteasomal degradation of Nod2 protein mediates tolerance to bacterial cell wall components. J Biol Chem. 2012;287:39800-11 pubmed publisher
    ..However, the mechanism underlying tolerance is not understood. Here, we show that activation of Nod2 by its ligand, muramyl dipeptide (MDP) in the bacterial cell wall, induces rapid degradation of Nod2, which confers ..
  14. Kim J, Omori E, Matsumoto K, Nunez G, Ninomiya Tsuji J. TAK1 is a central mediator of NOD2 signaling in epidermal cells. J Biol Chem. 2008;283:137-44 pubmed
    ..is a peptidoglycan moiety derived from commensal and pathogenic bacteria, and a ligand of its intracellular sensor NOD2. Mutations in NOD2 are highly associated with Crohn disease, which is characterized by dysregulated inflammation in ..
  15. Zurek B, Schoultz I, Neerincx A, Napolitano L, Birkner K, Bennek E, et al. TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation. PLoS ONE. 2012;7:e41255 pubmed publisher
    b>NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses...
  16. Seiderer J, Dambacher J, Leistner D, Tillack C, Glas J, Niess J, et al. Genotype-phenotype analysis of the CXCL16 p.Ala181Val polymorphism in inflammatory bowel disease. Clin Immunol. 2008;127:49-55 pubmed publisher
    ..009; OR 2.60; CI 1.29-5.25). Carriers of at least one Val allele and one CARD15/NOD2 variant had a higher incidence of a stricturing and penetrating phenotype (p=0.030, OR 4.04, CI 1.27-12...
  17. Simms L, Doecke J, Walsh M, Huang N, Fowler E, Radford Smith G. Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease. Gut. 2008;57:903-10 pubmed publisher
    ..alpha-defensin expression has been reported to be associated with Crohn's disease, especially in patients carrying NOD2 mutations...
  18. Mo J, Boyle J, Howard C, Monie T, Davis B, Duncan J. Pathogen sensing by nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is mediated by direct binding to muramyl dipeptide and ATP. J Biol Chem. 2012;287:23057-67 pubmed publisher
    Nucleotide binding and oligomerization domain-containing protein 2 (NOD2/Card15) is an intracellular protein that is involved in the recognition of bacterial cell wall-derived muramyl dipeptide...
  19. Condé C, Rambout X, Lebrun M, Lecat A, Di Valentin E, Dequiedt F, et al. The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-?B activation by disturbing the interaction of XIAP with RIP2. PLoS ONE. 2012;7:e41005 pubmed publisher
    ..Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling...
  20. Krieg A, Correa R, Garrison J, Le Negrate G, Welsh K, Huang Z, et al. XIAP mediates NOD signaling via interaction with RIP2. Proc Natl Acad Sci U S A. 2009;106:14524-9 pubmed publisher
    NOD1 and NOD2 are members of the NOD-like receptor (NLR) protein family that are involved in sensing the presence of pathogens and are a component of the innate immune system...
  21. Hsu L, Ali S, McGillivray S, Tseng P, Mariathasan S, Humke E, et al. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A. 2008;105:7803-8 pubmed publisher
    b>NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1beta...
  22. Deshmukh H, Hamburger J, Ahn S, McCafferty D, Yang S, Fowler V. Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infect Immun. 2009;77:1376-82 pubmed publisher
    b>NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role in the host response to Staphylococcus aureus infection is unknown...
  23. Glas J, Konrad A, Schmechel S, Dambacher J, Seiderer J, Schroff F, et al. The ATG16L1 gene variants rs2241879 and rs2241880 (T300A) are strongly associated with susceptibility to Crohn's disease in the German population. Am J Gastroenterol. 2008;103:682-91 pubmed
    ..Genotyping included CARD15/NOD2 variants p.Arg702Trp, p.Gly908Arg, and p...
  24. Parkhouse R, Boyle J, Mayle S, Sawmynaden K, Rittinger K, Monie T. Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker region between the NOD2 CARDs and NACHT domain. FEBS Lett. 2014;588:2830-6 pubmed publisher
    b>NOD2 activation by muramyl dipeptide causes a proinflammatory immune response in which the adaptor protein CARD9 works synergistically with NOD2 to drive p38 and c-Jun N-terminal kinase (JNK) signalling...
  25. Cantó E, Ricart E, Busquets D, Monfort D, Garcia Planella E, Gonzalez D, et al. Influence of a nucleotide oligomerization domain 1 (NOD1) polymorphism and NOD2 mutant alleles on Crohn's disease phenotype. World J Gastroenterol. 2007;13:5446-53 pubmed
    To examine genetic variation of nucleotide oligomerization domain 1 (NOD1) and NOD2, their respective influences on Crohn's disease phenotype and gene-gene interactions...
  26. Damgaard R, Nachbur U, Yabal M, Wong W, Fiil B, Kastirr M, et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012;46:746-58 pubmed publisher
    ..Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice...
  27. Travassos L, Carneiro L, Ramjeet M, Hussey S, Kim Y, Magalhaes J, et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol. 2010;11:55-62 pubmed publisher
    ..Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria...
  28. Ningappa M, Higgs B, Weeks D, Ashokkumar C, Duerr R, Sun Q, et al. NOD2 gene polymorphism rs2066844 associates with need for combined liver-intestine transplantation in children with short-gut syndrome. Am J Gastroenterol. 2011;106:157-65 pubmed publisher
    The nucleotide-binding oligomerization protein 2 (NOD2) gene single nucleotide polymorphisms (SNPs) associated with Crohn's disease were recently associated with severe rejection after small-bowel transplantation (SBTx)...
  29. Dusatkova P, Hradsky O, Lenicek M, Bronsky J, Nevoral J, Kotalova R, et al. Association of IL23R p.381Gln and ATG16L1 p.197Ala with Crohn disease in the Czech population. J Pediatr Gastroenterol Nutr. 2009;49:405-10 pubmed publisher
    ..02-1.52, P=0.03). There was no appreciable difference in the effect of the associated alleles across the strata of CARD15-conferred risk...
  30. Chen H, Lee A, Bowcock A, Zhu W, Li E, Ciorba M, et al. Influence of Crohn's disease risk alleles and smoking on disease location. Dis Colon Rectum. 2011;54:1020-5 pubmed publisher
    ..For statistical reasons, the 3 major NOD2 alleles (rs2066844, rs2066845, and rs2066847) were grouped together...
  31. Arostegui J, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P, et al. NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum. 2007;56:3805-13 pubmed
    Blau syndrome and early-onset sarcoidosis are NOD2 gene-associated chronic autoinflammatory diseases characterized by skin rash, arthritis, and/or eye involvement, with noncaseating granulomata as their pathologic hallmark...
  32. Magnowski P, Medrek K, Magnowska M, Stawicka M, Kedzia H, Gorski B, et al. The 3020insC NOD2 gene mutation in patients with ovarian cancer. Ginekol Pol. 2008;79:544-9 pubmed
    ..The role of mutations in NOD2 gene in this type of neoplasm is still under investigation. The aim of this study was to determine: 1...
  33. Bruns T, Peter J, Reuken P, Grabe D, Schuldes S, Brenmoehl J, et al. NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis. Liver Int. 2012;32:223-30 pubmed publisher
    ..Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study...
  34. Wex T, Ebert M, Kropf S, Dierkes J, Schüttler K, Rocken C, et al. Gene polymorphisms of the NOD-2/CARD-15 gene and the risk of gastric cancer in Germany. Anticancer Res. 2008;28:757-62 pubmed
    ..NOD-2 is not a risk factor for gastric carcinogenesis in the Caucasian population. ..
  35. Petterson T, Jendholm J, Mansson A, Bjartell A, Riesbeck K, Cardell L. Effects of NOD-like receptors in human B lymphocytes and crosstalk between NOD1/NOD2 and Toll-like receptors. J Leukoc Biol. 2011;89:177-87 pubmed publisher
    ..B cells were isolated and analyzed for mRNA and protein expression. The functional responsiveness of NOD1 and NOD2 was investigated upon stimulation with the cognate ligands, with or without stimulation via IgM/IgD/CD40 and/or ..
  36. Glas J, Seiderer J, Tillack C, Pfennig S, Beigel F, Jürgens M, et al. The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants. PLoS ONE. 2010;5:e14466 pubmed publisher
    The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences...
  37. Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med. 2010;16:90-7 pubmed publisher
    Nucleotide-binding oligomerization domain-containing-2 (NOD2) acts as a bacterial sensor in dendritic cells (DCs), but it is not clear how bacterial recognition links with antigen presentation after NOD2 stimulation...
  38. Till A, Rosenstiel P, Bräutigam K, Sina C, Jacobs G, Oberg H, et al. A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion. J Cell Sci. 2008;121:487-95 pubmed publisher
    b>NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide...
  39. Uehara A, Takada H. Synergism between TLRs and NOD1/2 in oral epithelial cells. J Dent Res. 2008;87:682-6 pubmed
    ..We found that NOD1 and NOD2 agonists, in combination with TLR agonists, synergistically induced production of PGRPs and of beta-defensin 2 in ..
  40. Marinis J, Homer C, McDonald C, Abbott D. A novel motif in the Crohn's disease susceptibility protein, NOD2, allows TRAF4 to down-regulate innate immune responses. J Biol Chem. 2011;286:1938-50 pubmed publisher
    The Crohn's disease and early onset sarcoidosis susceptibility protein, NOD2, coordinates innate immune signaling pathways...
  41. Pan H, Dai Y, Tang S, Wang J. Polymorphisms of NOD2 and the risk of tuberculosis: a validation study in the Chinese population. Int J Immunogenet. 2012;39:233-40 pubmed publisher
    A genome-wide association study (GWAS) of leprosy reported four specific genetic polymorphisms of NOD2 that were associated with susceptibility to Mycobacterium leprae in China...
  42. Ernst A, Jacobsen B, Østergaard M, Okkels H, Andersen V, Dagiliene E, et al. Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population. Scand J Gastroenterol. 2007;42:1445-51 pubmed
    Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations...
  43. Borm M, van Bodegraven A, Mulder C, Kraal G, Bouma G. The effect of NOD2 activation on TLR2-mediated cytokine responses is dependent on activation dose and NOD2 genotype. Genes Immun. 2008;9:274-8 pubmed publisher
    The mechanism by which mutations in NOD2 predispose to Crohn's disease (CD) is incompletely understood. In mice, NOD2 has been found to function as a negative regulator of Toll-like receptor 2 (TLR2) signaling...
  44. Hnatyszyn A, Szalata M, Stanczyk J, Cichy W, Slomski R. Association of c.802C>T polymorphism of NOD2/CARD15 gene with the chronic gastritis and predisposition to cancer in H. pylori infected patients. Exp Mol Pathol. 2010;88:388-93 pubmed publisher
    This paper shows analysis of the association of the 802C>T polymorphism of the NOD2/CARD15 gene with the occurrence of the chronic inflammation of the gastric mucosa associated with the Helicobacter pylori infections, development of ..
  45. Bielig H, Zurek B, Kutsch A, Menning M, Philpott D, Sansonetti P, et al. A function for AAMP in Nod2-mediated NF-kappaB activation. Mol Immunol. 2009;46:2647-54 pubmed publisher
    ..as a new binding partner of the human nucleotide-binding domain, leucine rich repeat containing (NLR) family member Nod2 in a yeast two-hybrid screen...
  46. Skibola C, Bracci P, Nieters A, Brooks Wilson A, de Sanjose S, Hughes A, et al. Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium. Am J Epidemiol. 2010;171:267-76 pubmed publisher
    ..rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes...
  47. Hradsky O, Lenicek M, Dusatkova P, Bronsky J, Nevoral J, Valtrova V, et al. Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs. Tissue Antigens. 2008;71:538-47 pubmed publisher
    Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response...
  48. Van Limbergen J, Nimmo E, Russell R, Drummond H, Smith L, Anderson N, et al. Investigation of NOD1/CARD4 variation in inflammatory bowel disease using a haplotype-tagging strategy. Hum Mol Genet. 2007;16:2175-86 pubmed
    Both NOD1/CARD4 and NOD2/CARD15 are intracellular pattern-recognition receptors involved in the innate immune response...
  49. Möckelmann N, von Schönfels W, Buch S, von Kampen O, Sipos B, Egberts J, et al. Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer. BMC Gastroenterol. 2009;9:79 pubmed publisher
    ..Several polymorphisms of the CARD15 gene (caspase activating recruitment domain, member 15) have been reported to be associated with an increased ..
  50. Zhao M, Jiang F, Zhang W, Li F, Wei L, Liu J, et al. A novel single nucleotide polymorphism within the NOD2 gene is associated with pulmonary tuberculosis in the Chinese Han, Uygur and Kazak populations. BMC Infect Dis. 2012;12:91 pubmed publisher
    The present study aimed to investigate the genetic polymorphisms in exon 4 of the NOD2 gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the NOD2 gene is associated with tuberculosis...
  51. Wagner R, Proell M, Kufer T, Schwarzenbacher R. Evaluation of Nod-like receptor (NLR) effector domain interactions. PLoS ONE. 2009;4:e4931 pubmed publisher
    ..Our results confirmed the interaction of NOD1 and NOD2 with RIPK2, and between NLRP3 and ASC, but most importantly, our studies revealed hitherto unrecognized ..
  52. Adler J, Rangwalla S, Dwamena B, Higgins P. The prognostic power of the NOD2 genotype for complicated Crohn's disease: a meta-analysis. Am J Gastroenterol. 2011;106:699-712 pubmed publisher
    ..Many studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2) mutations are associated with a varying but increased risk of complicated disease...
  53. Nguyen Y, Al Lehibi A, Gorbe E, Li E, Haagenson M, Wang T, et al. Insufficient evidence for association of NOD2/CARD15 or other inflammatory bowel disease-associated markers on GVHD incidence or other adverse outcomes in T-replete, unrelated donor transplantation. Blood. 2010;115:3625-31 pubmed publisher
    Previous European studies suggest NOD2/CARD15 and interleukin-23 receptor (IL-23R) donor or recipient variants are associated with adverse clinical outcomes in allogeneic hematopoietic stem cell transplantation...
  54. Glas J, Seiderer J, Wetzke M, Konrad A, Török H, Schmechel S, et al. rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PLoS ONE. 2007;2:e819 pubmed
    ..There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5...
  55. Zhao Y, Alonso C, Ballester I, Song J, Chang S, Guleng B, et al. Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflamm Bowel Dis. 2012;18:603-12 pubmed publisher
    Genetic variants of nucleotide-binding oligomerization domain 2 (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory diseases in patients with Crohn's disease (CD)...
  56. King A, Horne A, Hombach Klonisch S, Mason J, Critchley H. Differential expression and regulation of nuclear oligomerization domain proteins NOD1 and NOD2 in human endometrium: a potential role in innate immune protection and menstruation. Mol Hum Reprod. 2009;15:311-9 pubmed publisher
    ..Real-time PCR showed that NOD1 mRNA is constitutively expressed in endometrium. NOD2 is up-regulated in the late secretory phase of the menstrual cycle suggesting a role in menstruation...
  57. Ashton K, Proietto A, Otton G, Symonds I, McEvoy M, Attia J, et al. Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk. BMC Cancer. 2010;10:382 pubmed publisher
    ..in 191 endometrial cancer cases and 291 controls using real-time PCR: NOD1 (rs2075822, rs2907749, rs2907748), NOD2 (rs5743260, rs2066844, rs2066845), TLR2 (rs5743708), TLR4 (rs4986790) and TLR9 (rs5743836, rs187084)...
  58. Jürgens M, Brand S, Laubender R, Seiderer J, Glas J, Wetzke M, et al. The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease independent of the IL23R genotype. J Gastroenterol. 2010;45:721-31 pubmed publisher
    ..of concomitant intestinal stenosis in patients with fistulizing Crohn's disease (CD), including the NOD2/CARD15 and IL23R genotype status...
  59. von Kampen O, Lipinski S, Till A, Martin S, Nietfeld W, Lehrach H, et al. Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling. J Biol Chem. 2010;285:19921-6 pubmed publisher
    ..In the present study, we demonstrate a specific modulation of NOD2-induced signaling by CARD8 in intestinal epithelial cells...
  60. Cruickshank S, Wakenshaw L, Cardone J, Howdle P, Murray P, Carding S. Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival. World J Gastroenterol. 2008;14:5834-41 pubmed
    To investigate the function of NOD2 in colonic epithelial cells (CEC)...
  61. Sato H, Williams H, Spagnolo P, Abdallah A, Ahmad T, Orchard T, et al. CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis. Eur Respir J. 2010;35:324-30 pubmed publisher
    ..This study explored associations between CARD15 polymorphisms, CCR5 haplotype and distinct pulmonary sarcoidosis subtypes...
  62. Türe Ozdemir F, Gazouli M, Tzivras M, Panagos C, Bovaretos N, Petraki K, et al. Association of polymorphisms of NOD2, TLR4 and CD14 genes with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma. Anticancer Res. 2008;28:3697-700 pubmed
    ..The aim of this study was to evaluate the relationship between NOD2, TLR4 and CD14 genetic polymorphisms and the development of gastric MALT-lymphoma...
  63. Freire P, Portela F, Donato M, Figueiredo P, Ferreira M, Amaro P, et al. CARD15 mutations and colorectal cancer in a South European country. Int J Colorectal Dis. 2010;25:1211-9 pubmed publisher
    b>CARD15 mutations are associated with higher susceptibility to Crohn's disease (CD) and longstanding colonic CD increases the risk of developing colorectal cancer (CRC)...
  64. Brenmoehl J, Herfarth H, Gluck T, Audebert F, Barlage S, Schmitz G, et al. Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients. Intensive Care Med. 2007;33:1541-8 pubmed
    Genetic variants in the NOD2/CARD15 gene resulting in a diminished capacity to activate NF-kappaB in response to bacterial cell wall products have been associated with Crohn's disease (CD)...
  65. Suchy J, Kłujszo Grabowska E, Kładny J, Cybulski C, Wokołorczyk D, Szymanska Pasternak J, et al. Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk. BMC Cancer. 2008;8:112 pubmed publisher
    ..identified a suggestive tendency, linking the TNFalpha -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs)...
  66. Juyal G, Amre D, Midha V, Sood A, Seidman E, Thelma B. Evidence of allelic heterogeneity for associations between the NOD2/CARD15 gene and ulcerative colitis among North Indians. Aliment Pharmacol Ther. 2007;26:1325-32 pubmed
    Three common disease susceptibility variants in the NOD2 gene are associated with inflammatory bowel disease in Caucasians, but not in Asians...
  67. van Beelen A, Zelinkova Z, Taanman Kueter E, Muller F, Hommes D, Zaat S, et al. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity. 2007;27:660-9 pubmed
    ..primed human DCs to promote IL-17 production in memory Th cells through the nucleotide oligomerization domain 2 (NOD2)-ligand muramyldipeptide (MDP), a derivative of bacterial peptidoglycan...
  68. Holler E, Rogler G, Brenmoehl J, Hahn J, Greinix H, Dickinson A, et al. The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation. Int J Immunogenet. 2008;35:381-4 pubmed publisher
    Previous studies from our group indicated a role of SNPs within the innate immunity receptor NOD2/CARD15 as a risk factor for GvHD and treatment-related mortality allogeneic stem cell transplantation from HLA-identical siblings...
  69. Kim H, Shin T, Yang S, Seo M, Kim D, Kang S, et al. Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood. PLoS ONE. 2010;5:e15369 pubmed publisher
    ..In this study, we investigated whether NOD1 and NOD2 regulate the functions of human umbilical cord blood-derived MSCs (hUCB-MSCs)...
  70. Zhang F, Huang W, Chen S, Sun L, Liu H, Li Y, et al. Genomewide association study of leprosy. N Engl J Med. 2009;361:2609-18 pubmed publisher
    ..We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2...
  71. Ince A, Hatirnaz O, Ovunc O, Ozbek U. 1007fs, G908R, R702W mutations and P268S, IVS8+158 polymorphisms of the CARD15 gene in Turkish inflammatory bowel disease patients and their relationship with disease-related surgery. Dig Dis Sci. 2008;53:1683-92 pubmed
    b>CARD15 gene mutations may present different frequencies in populations and sometimes surgical interventions may become a necessary therapy for inflammatory bowel disease patients...
  72. Lappalainen M, Paavola Sakki P, Halme L, Turunen U, Farkkila M, Repo H, et al. Novel CARD15/NOD2 mutations in Finnish patients with Crohn's disease and their relation to phenotypic variation in vitro and in vivo. Inflamm Bowel Dis. 2008;14:176-85 pubmed
    Three mutations (R702W, G908R, and 1007fs) of the CARD15/NOD2 gene associate with Crohn's disease (CD)...
  73. Shigeoka A, Kambo A, Mathison J, King A, Hall W, da Silva Correia J, et al. Nod1 and nod2 are expressed in human and murine renal tubular epithelial cells and participate in renal ischemia reperfusion injury. J Immunol. 2010;184:2297-304 pubmed publisher
    Nucleotide-binding oligomerization domain (Nod) 1 and Nod2 are members of a family of intracellular innate sensors that participate in innate immune responses to pathogens and molecules released during the course of tissue injury, ..
  74. Lv C, Yang X, Zhang Y, Zhao X, Chen Z, Long J, et al. Confirmation of three inflammatory bowel disease susceptibility loci in a Chinese cohort. Int J Colorectal Dis. 2012;27:1465-72 pubmed publisher
    ..Then, an extended analysis of the relationship between genotype and phenotype was performed. NOD2-P268S (P = 0.025) was found to contribute susceptibility to CD in the Chinese population...
  75. Sabbah A, Chang T, Harnack R, Frohlich V, Tominaga K, Dube P, et al. Activation of innate immune antiviral responses by Nod2. Nat Immunol. 2009;10:1073-80 pubmed publisher
    ..Here we show that nucleotide-binding oligomerization domain 2 (Nod2) can also function as a cytoplasmic viral PRR by triggering activation of interferon-regulatory factor 3 (IRF3) and ..
  76. Yazdanyar S, Weischer M, Nordestgaard B. Genotyping for NOD2 genetic variants and crohn disease: a metaanalysis. Clin Chem. 2009;55:1950-7 pubmed publisher
    ..and Leu1007fsinsC variants of the NOD2 gene (nucleotide-binding oligomerization domain containing 2; alias, CARD15) influence the risk of Crohn disease...
  77. Strober W, Kitani A, Fuss I, Asano N, Watanabe T. The molecular basis of NOD2 susceptibility mutations in Crohn's disease. Mucosal Immunol. 2008;1 Suppl 1:S5-9 pubmed publisher
    ..It is thus somewhat paradoxical that polymorphisms in the gene that encode NOD2 (CARD15) that lead to impaired NOD2 function, are susceptibility factors in Crohn's disease, a condition marked by ..
  78. van der Velden W, Blijlevens N, Maas F, Schaap N, Jansen J, van der Reijden B, et al. NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation. Bone Marrow Transplant. 2009;44:243-8 pubmed publisher
    Single nucleotide polymorphisms (SNPs) in the NOD2 gene have significant impact on both treatment-related mortality (TRM) and acute GVHD (aGVHD) in haematopoietic stem cell transplantation (HSCT)...
  79. Szeliga J, Sondka Z, Jackowski M, Jarkiewicz Tretyn J, Tretyn A, Malenczyk M. NOD2/CARD15 polymorphism in patients with rectal cancer. Med Sci Monit. 2008;14:CR480-4 pubmed
    ..have not provided conclusive evidence regarding a relationship between the development of colorectal cancer and NOD2 gene mutations, though some geographic variability has been shown...
  80. van Rijn B, Franx A, Steegers E, de Groot C, Bertina R, Pasterkamp G, et al. Maternal TLR4 and NOD2 gene variants, pro-inflammatory phenotype and susceptibility to early-onset preeclampsia and HELLP syndrome. PLoS ONE. 2008;3:e1865 pubmed publisher
    ..of the innate immune receptors Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 2 (NOD2), that impair the inflammatory response to endotoxin, are related to preeclampsia and HELLP syndrome...
  81. Akahoshi M, Ishihara M, Namba K, Kitaichi N, Ando Y, Takenaka S, et al. Mutation screening of the CARD15 gene in sarcoidosis. Tissue Antigens. 2008;71:564-7 pubmed publisher
    b>CARD15 was first identified as a susceptibility gene for Crohn's disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early-onset sarcoidosis (EOS)...
  82. Singh V, Gaur R, Mittal M, Biswas S, Das R, Girdhar B, et al. Absence of nucleotide-binding oligomerization domain-containing protein 2 variants in patients with leprosy and tuberculosis. Int J Immunogenet. 2012;39:353-6 pubmed publisher
    ..This is the first report to suggest the minimal role of these variants in susceptibility/resistance to TB and leprosy in this population. ..
  83. Gasche C, Nemeth M, Grundtner P, Willheim Polli C, Ferenci P, Schwarzenbacher R. Evolution of Crohn's disease-associated Nod2 mutations. Immunogenetics. 2008;60:115-20 pubmed publisher
    Several lines of evidence have confirmed the importance of Nod2 mutations for disease susceptibility in Crohn's disease...
  84. Molnar T, Hofner P, Nagy F, Lakatos P, Fischer S, Lakatos L, et al. NOD1 gene E266K polymorphism is associated with disease susceptibility but not with disease phenotype or NOD2/CARD15 in Hungarian patients with Crohn's disease. Dig Liver Dis. 2007;39:1064-70 pubmed
    ..The different polymorphisms of pattern-recognition receptors (e.g. NOD2/CARD15 SNP8, SNP12 and SNP13 mutations, the TLR4 D299G polymorphism and NOD1 G796A) did not reveal a mutual basis...
  85. Tigno Aranjuez J, Bai X, Abbott D. A discrete ubiquitin-mediated network regulates the strength of NOD2 signaling. Mol Cell Biol. 2013;33:146-58 pubmed publisher
    Dysregulation of NOD2 signaling is implicated in the pathology of various inflammatory diseases, including Crohn's disease, asthma, and sarcoidosis, making signaling proteins downstream of NOD2 potential therapeutic targets...