rs12720356

This is a protein-altering variant in the TYK2 gene.

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GWAS Catalog Trait Associations (11)

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

interferon alpha/beta receptor 1 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.17
p 2.0e-83
N 47,745
Large GWAS
European
Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele C
OR 0.17
p 3.0e-14
N 10,708
Large GWAS
European

level of bone marrow stromal antigen 2 in blood

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.12
p 1.0e-40
N 47,745
Large GWAS
European

interleukin-12 receptor subunit beta-1 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR 0.11
p 5.0e-36
N 47,745
Large GWAS
European

body height

Yengo L et al. “A saturated map of common genetic variants associated with human height.” Nature 610(7933):704-712 (2022)
Allele C
OR 0.01
p 4.0e-30
N 5,314,291
Large GWAS
European, Hispanic or Latin American, East Asian, African unspecified, South Asian

inflammatory bowel disease

Liu JZ et al. “Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.” Nature Genetics 47(9):979-986 (2015)
Allele C
OR 1.16
p 4.0e-16
N 34,652
Large GWAS
multi-ancestry
Wu Y et al. “GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression.” Nature Communications 12(1):1146 (2021)
Allele C
OR 0.86
p 2.0e-8
N 456,327
Large GWAS
European

Crohn's disease

Franke A et al. “Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.” Nature Genetics 42(12):1118-25 (2010)
Allele G
OR 1.12
p 1.0e-12
N 21,389
Meta-analysisLarge GWAS
European
Liu JZ et al. “Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.” Nature Genetics 47(9):979-986 (2015)
Allele G
OR 1.15
p 3.0e-11
N 20,883
Large GWAS
multi-ancestry

psoriasis

Strange A et al. “A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.” Nature Genetics 42(11):985-990 (2010)
Allele A
OR 1.40
p 4.0e-11
N 7,353
Large GWAS
European
Tsoi LC et al. “Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity.” Nature Genetics 44(12):1341-8 (2012)
Allele A
OR 1.25
p 3.0e-10
N 33,394
Large GWAS
European

rheumatoid arthritis

Saevarsdottir S et al. “Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset.” Annals of the Rheumatic Diseases 81(8):1085-1095 (2022)
Allele C
OR 0.90
p 4.0e-10
N 1,026,690
Large GWAS
European
Ishigaki K et al. “Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.” Nature Genetics 54(11):1640-1651 (2022)
Allele C
OR 0.87
p 8.0e-9
N 276,020
Large GWAS
multi-ancestry

lean body mass

Harris BHL et al. “New role of fat-free mass in cancer risk linked with genetic predisposition.” Scientific Reports 14(1):7270 (2024)
Allele C
OR 0.01
p 6.0e-10
N 337,739
Large GWAS
European
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ClinVar annotation

Benign★★★☆
7 submitters10 publications

Immunodeficiency 35 (IMD35); not specified

View on ClinVar →
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Research that mentions this SNP (7)

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Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population
AssociationN=1,284Liang Tang et al.(2015)· Inflammation Research

Case-control study in 642 Han Chinese SLE patients and 642 healthy controls examining polymorphisms in IRF5 and TYK2 genes. IRF5 rs2004640 (T allele, OR=1.41, p=0.0003) and protective haplotype DAG (OR=0.71, p=6.2×10⁻⁵) and risk haplotype IAT (OR=1.53, p=0.0005) showed significant association with SLE. TYK2 rs280500 (A allele, OR=1.47, p=8.83×10⁻⁶), rs2304256 (G allele, OR=1.59, p=3.71×10⁻⁶), and rs8108236 (A allele, OR=1.39, p=0.0004) were significantly associated with SLE. A three-way gene-gene interaction between TYK2 rs280500, rs2304256 and IRF5 rs10954213 was found (p<0.0001).

Traits studied:Systemic Lupus Erythematosus
PubMedDOIMetascience Observatory
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Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis
Meta-analysisN=24,286Young Ho Lee et al.(2012)· Inflammation Research

This meta-analysis of 13 studies examined associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus (SLE) susceptibility. The rs6445975 polymorphism in PXK was significantly associated with increased SLE risk in Europeans (OR = 1.198, P = 3.4E-07) but not Asians. The rs2304256 polymorphism in TYK2 showed a protective association with SLE in Europeans (OR = 0.700, P = 1.3E-04) but not Asians. Other TYK2 variants (rs12720270, rs280519, rs12720356) showed no significant associations.

Traits studied:Systemic lupus erythematosus
PubMedDOIMetascience Observatory
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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)
PubMedDOIMetascience Observatory
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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
PubMedDOIMetascience Observatory
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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
PubMedDOIMetascience Observatory
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Variants in interferon‐alpha pathway genes and response to pegylated interferon‐Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long‐term treatment against cirrhosis trial†‡
AssociationN=712Tania Mara Welzel et al.(2009)· Hepatology

In the HALT-C trial of 581 European American patients with advanced chronic hepatitis C, genetic variants in the interferon-alpha pathway were associated with sustained virological response (SVR) to pegylated interferon-alpha-2a plus ribavirin therapy. Key associations included IFNAR1 IVS1-22G (aOR=0.57, p=0.02), IFNAR2 Ex2-33C (aOR=2.09, p=0.02), JAK1 IVS22+112T (aOR=1.66, p=0.04), and ADAR Ex9+14A (aOR=1.67, p=0.03). The TYK2 -2256A promoter variant showed a borderline association in European Americans (OR=1.51, p=0.05) but a strong association in African American patients (p=0.006).

Traits studied:Chronic hepatitis C infectionHepatitis C virus (HCV) treatment responseSustained virological response (SVR)
PubMedDOIMetascience Observatory
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Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population
AssociationN=7,457Maarit Lappalainen et al.(2008)· Inflammatory Bowel Diseases

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

Traits studied:Acute anterior uveitis (AAU)Ankylosing spondylitis (AS)Spondyloarthropathies
PubMedDOIMetascience Observatory

About TYK2

This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with Immunodeficiency 35. [provided by RefSeq, Sep 2020]

View all TYK2 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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