IL23R R381Q - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

IL23R R381Q

(IL23R Arg381Gln)


Short summary

confers strong protection against Crohn’s disease
Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr1:67705958: 4.8% (513/10756) in EVS
  • A @ chr1:67478545: 3.1% (4/128) in GET-Evidence
  • Frequency shown in summary reports: 4.8% (513/10756)

Publications
 

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. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26. PubMed PMID: 17068223.

 

Hollis-Moffatt JE, Merriman ME, Rodger RA, Rowley KA, Chapman PT, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PB, O'Donnell JL, Stamp LK, Merriman TR. Evidence for association of an interleukin 23 receptor variant independent of the R381Q variant with rheumatoid arthritis. Ann Rheum Dis. 2009 Aug;68(8):1340-4. doi: 10.1136/ard.2008.090142. Epub 2008 Jul 22. PubMed PMID: 18647855.

 

Kenny EE, Pe'er I, Karban A, Ozelius L, Mitchell AA, Ng SM, Erazo M, Ostrer H, Abraham C, Abreu MT, Atzmon G, Barzilai N, Brant SR, Bressman S, Burns ER, Chowers Y, Clark LN, Darvasi A, Doheny D, Duerr RH, Eliakim R, Giladi N, Gregersen PK, Hakonarson H, Jones MR, Marder K, McGovern DP, Mulle J, Orr-Urtreger A, Proctor DD, Pulver A, Rotter JI, Silverberg MS, Ullman T, Warren ST, Waterman M, Zhang W, Bergman A, Mayer L, Katz S, Desnick RJ, Cho JH, Peter I. A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. PLoS Genet. 2012;8(3):e1002559. doi: 10.1371/journal.pgen.1002559. Epub 2012 Mar 8. PubMed PMID: 22412388; PubMed Central PMCID: PMC3297573.

 

Genomes
 

 

 

 

 

 

GS18501 - var-GS18501-1100-36-ASM
het A @ chr1:67478546

 

GS19669 - var-GS19669-1100-36-ASM
het A @ chr1:67478546

 

GS19670 - var-GS19670-1100-36-ASM
hom A @ chr1:67478546

 

Other external references
 

    dbSNP
  • rs11209026
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GWAS
  • Ulcerative colitis (rs11209026-?)
    Barrett 15-Nov-09 in Nat Genet
    OR or beta: NR NR
    p-value: 3.00E-10
    Initial sample: 2,361 European ancestry cases, 5,417 European ancestry controls
    Replication sample: 2,321 European ancestry cases, 4,818 European ancestry controls
    www.ncbi.nlm.nih.gov/pubmed/19915572
  • Ulcerative colitis (rs11209026-?)
    Silverberg 4-Jan-09 in Nat Genet
    OR or beta: 1.79
    Risk allele frequency: 0.93
    p-value: 1.00E-08
    Initial sample: 1,022 cases, 2,503 controls
    Replication sample: 1,387 cases, 1,115 controls
    www.ncbi.nlm.nih.gov/pubmed/19122664
  • Inflammatory bowel disease (rs11209026-?)
    Kugathasan 31-Aug-08 in Nat Genet
    OR or beta: 2.56 [1.92-3.45]
    Risk allele frequency: 0.94
    p-value: 7.00E-11
    Initial sample: 1,011 cases, 4,250 controls
    Replication sample: 1,922 cases, 14,124 controls
    www.ncbi.nlm.nih.gov/pubmed/18758464
  • Crohn's disease (rs11209026-?)
    Libioulle 5-Mar-07 in PLoS Genet
    OR or beta: 2.92 [NR]
    Risk allele frequency: 0.92
    p-value: 2.00E-18
    Initial sample: 547 cases, 928 controls
    Replication sample: 1,266 cases, 559 controls, 428 trios
    www.ncbi.nlm.nih.gov/pubmed/17447842
  • Inflammatory bowel disease (rs11209026-A)
    Duerr 26-Oct-06 in Science
    OR or beta: 3.84 [2.33-6.66]
    Risk allele frequency: 0.93
    p-value: 4.00E-11
    Initial sample: 547 cases, 548 controls
    Replication sample: 401 cases, 433 controls, 883 families, 1,119 affected offspring
    www.ncbi.nlm.nih.gov/pubmed/17068223
    PharmGKB
  • [Crohn Disease]
    The A allele of rs11209026 was shown to be associated with protection from Crohn's disease in GWAS of two white case-control cohorts(one Jewish, one non-Jewish).
    www.ncbi.nlm.nih.gov/pubmed/17068223
  • [Inflammatory Bowel Diseases]
    GWAS Results: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene (Initial Sample Size: 547 cases, 548 controls; Replication Sample Size: 401 cases, 433 controls, 883 families, 1,119 affected offspring; Risk Allele: rs11209026-A).
    www.ncbi.nlm.nih.gov/pubmed/17068223; Web Resource:http://www.genome.gov/gwastudie
  • [Crohn Disease]
    GWAS results: Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci (Initial Sample Size: 382 trios; Replication Sample Size: 521 trios, 750 cases, 828 controls). This variant is associated with Crohn's disease. This variant is associated with Crohn's disease.
    www.ncbi.nlm.nih.gov/pubmed/17804789; Web Resource:http://www.genome.gov/gwastudie
  • [Colitis, Ulcerative]
    GWAS results: Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. (Initial Sample Size: 1,022 cases, 2,503 controls; Replication Sample Size: 1,387 cases, 1,115 controls); (Region: 1p31.3; Reported Gene(s): IL23R; Risk Allele: rs11209026-?); (p-value= 0.00000001).This variant is associated with Ulcerative colitis.
    www.ncbi.nlm.nih.gov/pubmed/19122664; Web Resource:http://www.genome.gov/gwastudie
    PolyPhen-2
  • Score: 0.997 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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