Gene: NOD2

Alternate names for this Gene: ACUG|BLAU|BLAUS|CARD15|CD|CLR16.3|IBD1|NLRC2|NOD2B|PSORAS1|YAOS

Gene Summary: This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Gene is located in Chromosome: 16

Location in Chromosome : 16q12.1

Description of this Gene: nucleotide binding oligomerization domain containing 2

Type of Gene: protein-coding

rs2066845 in NOD2 gene and Ankylosing spondylitis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs199883290 in NOD2 gene and Asthma PMID 21150878 2011 Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia.

PMID 30929738 2019 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

rs2066844 in NOD2 gene and Childhood asthma PMID 30929738 2019 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

PMID 31036433 2019 Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies.

rs2066845 in NOD2 gene and Cholangitis, Sclerosing PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs104895420 in NOD2 gene and Crohn Disease PMID 27812135 2016 Characterization and Genetic Analyses of New Genes Coding for NOD2 Interacting Proteins.

PMID 24960071 2014 Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker region between the NOD2 CARDs and NACHT domain.

PMID 15024686 2004 Crohn disease: frequency and nature of CARD15 mutations in Ashkenazi and Sephardi/Oriental Jewish families.

PMID 24790089 2014 The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.

PMID 11385576 2001 Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

PMID 16485124 2006 Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease.

PMID 17554300 2007 Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

PMID 17804789 2007 Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci.

PMID 17684544 2007 Systematic association mapping identifies NELL1 as a novel IBD disease gene.

PMID 23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

PMID 18587394 2008 Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.

PMID 20570966 2010 Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease.

PMID 17068223 2006 A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.

PMID 16485124 2006 We performed a limited DNA sequence analysis of the CARD15 gene in 89 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and three patients with indeterminate colitis (IC), who were heterozygous carriers of one of the common CARD15 mutations [c.2104C>T (p.R702W), c.2722G>C (p.G908R), or c.3019_3020insC (p.Leu1007fsX1008)], the c.2462+10A>C variant, or of a new amino acid substitution in the 3'-end of exon 4.

PMID 28067908 2017 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.

PMID 27812135 2016 Additionally, we show that the interaction of 8 NIPs is compromised with the 3 main CD associated NOD2 mutants (R702W, G908R and 1007fs).

PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

PMID 27812135 2016 Additionally, we show that the interaction of 8 NIPs is compromised with the 3 main CD associated NOD2 mutants (R702W, G908R and 1007fs).

PMID 15024686 2004 A higher frequency of CARD15 mutations was found in AJ patients from multiplex families with CD from Central (44.0%) versus Eastern (24.0%) Europe, especially for G908R and 1007fs, and in SOJ patients (34.5%) compared with AJ (10.1%) or SOJ (5.4%) controls.

PMID 16485124 2006 We performed a limited DNA sequence analysis of the CARD15 gene in 89 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and three patients with indeterminate colitis (IC), who were heterozygous carriers of one of the common CARD15 mutations [c.2104C>T (p.R702W), c.2722G>C (p.G908R), or c.3019_3020insC (p.Leu1007fsX1008)], the c.2462+10A>C variant, or of a new amino acid substitution in the 3'-end of exon 4.

PMID 22936669 2013 A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300.

PMID 21102463 2010 Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

PMID 22412388 2012 A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.

PMID 17435756 2007 Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis.

PMID 17447842 2007 Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.

rs2066844 in NOD2 gene and Inflammatory Bowel Diseases PMID 28067908 2017 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.

PMID 17068223 2006 A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.

PMID 18758464 2008 Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.

rs2066844 in NOD2 gene and Oral Ulcer PMID 30837455 2019 Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci.

rs2066845 in NOD2 gene and Psoriasis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs104895462 in NOD2 gene and Regional enteritis PMID 17157607 2006 Blau syndrome associated with a CARD15/NOD2 mutation.

PMID 14522785 2003 Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation.

PMID 11528384 2001 CARD15 mutations in Blau syndrome.

PMID 22509093 2012 NOD2/CARD15 gene mutation identified in a Chinese family with Blau syndrome.

PMID 15044951 2004 Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition.

PMID 15459013 2005 Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome.

PMID 24713464 2014 Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome.

PMID 25416713 2015 Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes.

PMID 21983784 2011 Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.

PMID 25829188 2015 Ex vivo and in vitro production of pro-inflammatory cytokines in Blau syndrome.

PMID 25136265 2014 Blau syndrome, the prototypic auto-inflammatory granulomatous disease.

PMID 25093298 2014 Blau syndrome polymorphisms in NOD2 identify nucleotide hydrolysis and helical domain 1 as signalling regulators.

PMID 19479836 2009 Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree.

PMID 27339507 2016 A Case of Blau Syndrome with NOD2 E383K Mutation.

PMID 20565245 2010 Familial case of Blau syndrome associated with a CARD15/NOD2 mutation.

PMID 18718560 2009 Clinical and genetic aspects of Blau syndrome: a 25-year follow-up of one family and a literature review.

PMID 15812565 2005 A new CARD15 mutation in Blau syndrome.

PMID 15024686 2004 Crohn disease: frequency and nature of CARD15 mutations in Ashkenazi and Sephardi/Oriental Jewish families.

PMID 18240302 2008 Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria.

PMID 11385576 2001 Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

PMID 12512038 2003 Crohn's disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan.

PMID 22684479 2013 The intermediate filament protein, vimentin, is a regulator of NOD2 activity.

PMID 15571588 2004 Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis.

PMID 15770725 2005 Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype-genotype correlations.

PMID 15198989 2004 Regulation of IL-8 and IL-1beta expression in Crohn's disease associated NOD2/CARD15 mutations.

PMID 19713276 2009 Genotyping for NOD2 genetic variants and crohn disease: a metaanalysis.

PMID 21274544 2011 NOD2 exonic variations in Iranian Crohn's disease patients.

PMID 18489434 2008 Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs.

PMID 21548950 2011 Evaluation of 22 genetic variants with Crohn's disease risk in the Ashkenazi Jewish population: a case-control study.

PMID 15190267 2004 NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

PMID 21335489 2011 Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.

PMID 11910337 2002 The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease.

PMID 11425413 2001 Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

PMID 12019468 2002 CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure.

PMID 11385577 2001 A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.

PMID 26500656 2015 Dysfunctional Crohn's Disease-Associated NOD2 Polymorphisms Cannot be Reliably Predicted on the Basis of RIPK2 Binding or Membrane Association.

rs104895462 in NOD2 gene and SYNOVITIS, GRANULOMATOUS, WITH UVEITIS AND CRANIAL NEUROPATHIES (disorder) PMID 15044951 2004 Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition.

PMID 24713464 2014 Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome.

PMID 15459013 2005 Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles.

PMID 25416713 2015 Of the 31 patients, 11 carried the p.R334W NOD2 mutation, 9 the p.R334Q and 11 various other NOD2 missense mutations; 20 patients were sporadic and 11 from five BS pedigrees.

PMID 14522785 2003 Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation.

PMID 22509093 2012 The R334W mutation in NOD2/CARD15 caused Blau syndrome in a Chinese pedigree.

PMID 17157607 2006 Blau syndrome associated with a CARD15/NOD2 mutation.

PMID 11528384 2001 CARD15 mutations in Blau syndrome.

PMID 21983784 2011 Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.

PMID 20565245 2010 Familial case of Blau syndrome associated with a CARD15/NOD2 mutation.

PMID 25136265 2014 Blau syndrome, the prototypic auto-inflammatory granulomatous disease.

PMID 25829188 2015 The objective was to study both ex vivo and in vitro secretion of pro-inflammatory cytokines in patients affected by Blau syndrome (BS) and carrying p.E383K mutation in the CARD15/NOD2 gene associated with the disease.

PMID 15812565 2005 In an Italian family with BS, we detected a novel mutation E383K, whose pathogenicity is strongly supported by cosegregation with the disease in the family and absence in controls, and by the evolutionary conservation and structural role of the affected glutamate close to the Walker B motif of the nucleotide-binding site in the NACHT domain.

PMID 18718560 2009 Clinical and genetic aspects of Blau syndrome: a 25-year follow-up of one family and a literature review.

PMID 27339507 2016 Although Blau syndrome has been reported as a genetic disease with high penetrance, asymptomatic carrier cases of a family with the same E383K mutation have also been reported.

PMID 19479836 2009 Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree.

PMID 25093298 2014 Blau syndrome polymorphisms in NOD2 identify nucleotide hydrolysis and helical domain 1 as signalling regulators.

PMID 15770725 2005 Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype-genotype correlations.

PMID 21274544 2011 NOD2 exonic variations in Iranian Crohn's disease patients.

PMID 11385576 2001 Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

PMID 19713276 2009 Genotyping for NOD2 genetic variants and crohn disease: a metaanalysis.

PMID 15024686 2004 Crohn disease: frequency and nature of CARD15 mutations in Ashkenazi and Sephardi/Oriental Jewish families.

PMID 22684479 2013 The intermediate filament protein, vimentin, is a regulator of NOD2 activity.

PMID 15198989 2004 Regulation of IL-8 and IL-1beta expression in Crohn's disease associated NOD2/CARD15 mutations.

PMID 15571588 2004 Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis.

PMID 21548950 2011 Evaluation of 22 genetic variants with Crohn's disease risk in the Ashkenazi Jewish population: a case-control study.

PMID 18489434 2008 Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs.

PMID 18240302 2008 Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria.

PMID 12512038 2003 Crohn's disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan.

PMID 15190267 2004 NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

PMID 21335489 2011 Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.

PMID 11385577 2001 A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.

PMID 11425413 2001 Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

PMID 12019468 2002 CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure.

PMID 11910337 2002 The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease.

PMID 26500656 2015 Dysfunctional Crohn's Disease-Associated NOD2 Polymorphisms Cannot be Reliably Predicted on the Basis of RIPK2 Binding or Membrane Association.

rs2066845 in NOD2 gene and Ulcerative Colitis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs2066844 in NOD2 gene and Yao syndrome PMID 26070941 2015 NOD2-associated autoinflammatory disease: a large cohort study.

PMID 21914217 2011 A new category of autoinflammatory disease associated with NOD2 gene mutations.