rs2305743

This variant is located in the IL12RB1 gene.

GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

systemic scleroderma

Allele A
OR 0.06
p 2.0e-8
N 140,706
Large GWAS
multi-ancestry

ClinVar annotation

Benign☆☆☆
1 submitter1 publication

not specified

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Research that mentions this SNP (3)

Brief Report: Candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity
ReviewEugénie Koumakis et al.(2012)· Arthritis &amp; Rheumatism

This review article by Ota and Kuwana synthesizes genetic studies on systemic sclerosis (SSc), a complex autoimmune disease. Multiple genetic association studies, including GWAS and candidate gene approaches, have identified SSc susceptibility genes primarily involved in innate immunity (IRF4, IRF5, IRF7, IRF8, TNFAIP3), adaptive immune response (TNFSF4, CD247, PTPN22, CSK, STAT4, BLK), IL-12 signaling (IL-12A, IL-12RB1, IL-12RB2, TYK2), apoptosis/autophagy (ATG5, GSDMA, GSDMB, NOTCH4), and vascular homeostasis/fibrosis (PPARG). The review emphasizes that identified risk variants are predominantly located in non-coding regulatory regions and influence gene expression rather than protein structure.

Traits studied:Anti-PM-SclAnti-RNA polymerase IIIAnti-U1RNPAnti-topoisomerase I (anti-topo I)Anticentromere antibody (ACA)Diffuse cutaneous SSc (dcSSc)Interstitial lung disease (ILD)Limited cutaneous SSc (lcSSc)Raynaud's phenomenonSSc-related autoantibodiesSystemic sclerosis (SSc)
Association of the FAM167A–BLK region with systemic sclerosis
ReviewIkue Ito et al.(2010)· Arthritis &amp; Rheumatism

This is a comprehensive review of genetic factors in systemic sclerosis (SSc), a complex autoimmune disease. The review synthesizes findings from candidate gene analysis and genome-wide association studies identifying numerous SNPs and genetic variants associated with SSc susceptibility, primarily in genes involved in innate immunity (IRF4, IRF5, IRF7, IRF8, TNFAIP3), adaptive immunity (TNFSF4, PTPN22, STAT4, BLK, PRDM1), and cell death pathways (ATG5, DNASE1L3, GSDMA/B, NOTCH4). HLA class II genes are associated with SSc-related autoantibodies rather than SSc itself, with DRB1 alleles carrying the FLEDR amino acid sequence critical for anti-topo I antibody responses.

Traits studied:Anti-PM-Scl antibodyAnti-RNA polymerase III antibodyAnti-U1RNP antibodyAnti-centromere antibodyAnti-topoisomerase I antibodyDiffuse cutaneous systemic sclerosisLimited cutaneous systemic sclerosisSSc-related interstitial lung diseaseSystemic sclerosis
Association of a KCNA5 gene polymorphism with systemic sclerosis–associated pulmonary arterial hypertension in the European Caucasian population
ReviewWipff J. et al.(2010)· Arthritis &amp; Rheumatism

This review updates knowledge on genetic factors in systemic sclerosis (SSc) susceptibility and disease expression. GWAS and candidate gene studies have identified multiple SSc-associated genetic variants primarily located in non-coding regions that influence gene expression through eQTL effects. Major risk genes include those involved in innate immunity (IRF4, IRF5, IRF7, IRF8, TNFAIP3), adaptive immune response (PTPN22, STAT4, TNFSF4, CD247), and cell death pathways (ATG5), while few genes directly involve fibrosis or vascular homeostasis. HLA class II genes associate with SSc-related autoantibodies rather than SSc itself. Multi-omics approaches are needed to characterize the complex molecular architecture and identify biomarkers.

Traits studied:Anti-topoisomerase I antibodiesAnticentromere antibodiesDiffuse cutaneous systemic sclerosisInterstitial lung diseaseLimited cutaneous systemic sclerosisPulmonary fibrosisSSc-related autoantibodiesSystemic sclerosis

About IL12RB1

The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

View all IL12RB1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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