rs11889341

This is a intron variant variant in the STAT4 gene.

▶

GWAS Catalog Trait Associations (12)

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

systemic lupus erythematosus

Yin X et al. “Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.” Annals of the Rheumatic Diseases 80(5):632-640 (2021)
Allele T
OR 1.41
p 5.0e-123
N 208,370
Meta-analysisLarge GWAS
East Asian
Bentham J et al. “Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.” Nature Genetics 47(12):1457-1464 (2015)
Allele T
OR 1.73
p 6.0e-122
N 14,267
Large GWAS
European
Alarcón-Riquelme ME et al. “Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.” Arthritis & Rheumatology (hoboken, N.j.) 68(4):932-43 (2016)
Allele T
OR 1.50
p 7.0e-13
N 3,710
Large GWAS
Hispanic or Latin American, Native American

hypothyroidism

White SL et al. “Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.” Nature Genetics 58(2):307-316 (2026)
Allele T
OR 0.09
p 1.0e-98
N 1,786,062
Large GWAS
European
Rand SA et al. “Genome-wide association study and polygenic risk prediction of hypothyroidism.” Nature Genetics 57(12):3007-3015 (2025)
Allele T
OR 0.11
p 3.0e-79
N 1,178,661
Large GWAS
European

Thyroid preparation use measurement

Wu Y et al. “Genome-wide association study of medication-use and associated disease in the UK Biobank.” Nature Communications 10(1):1891 (2019)
Allele T
OR 0.14
p 3.0e-39
N 305,582
Major Consortium StudyLarge GWAS
European

rheumatoid arthritis

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 T
OR 1.14
p 2.0e-31
N 276,020
Large GWAS
multi-ancestry
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele T
OR 0.12
p 3.0e-17
N 595,872
Large GWAS
multi-ancestry
Ha E et al. “Large-scale meta-analysis across East Asian and European populations updated genetic architecture and variant-driven biology of rheumatoid arthritis, identifying 11 novel susceptibility loci.” Annals of the Rheumatic Diseases 80(5):558-565 (2021)
Allele T
OR 1.16
p 4.0e-30
N 311,292
Meta-analysisLarge GWAS
multi-ancestry
Okada Y et al. “Genetics of rheumatoid arthritis contributes to biology and drug discovery.” Nature 506(7488):376-381 (2014)
Allele T
OR 1.12
p 1.0e-12
N 79,799
Large GWAS
multi-ancestry
Laufer VA et al. “Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.” Human Molecular Genetics 28(5):858-874 (2019)
Allele T
OR 0.16
p 6.0e-9
N 2,308
Large GWAS
multi-ancestry

primary biliary cirrhosis

Cordell HJ et al. “An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.” Journal of Hepatology 75(3):572-581 (2021)
Allele T
OR 0.25
p 3.0e-31
N 31,288
Meta-analysisLarge GWAS
multi-ancestry

systemic scleroderma

Ishikawa Y et al. “GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.” Nature Communications 15(1):319 (2024)
Allele T
OR 0.16
p 3.0e-20
N 114,027
Large GWAS
East Asian

juvenile idiopathic arthritis

López-Isac E et al. “Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms.” Annals of the Rheumatic Diseases 80(3):321-328 (2021)
Allele T
OR 1.26
p 2.0e-19
N 12,501
Large GWAS
European

limited scleroderma

Ishikawa Y et al. “GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.” Nature Communications 15(1):319 (2024)
Allele T
OR 1.49
p 5.0e-12
N 113,278
Large GWAS
East Asian
▶

Research that mentions this SNP (4)

▶
Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans
AssociationN=5,422Christopher J. Lessard et al.(2016)· Arthritis &amp; Rheumatology

Genome-wide association study in 1,174 Korean SLE cases and 4,248 controls identified 12 genome-wide significant loci, including a novel locus spanning ATG16L2, FCHSD2, and P2RY2 peaking at rs11235667 (P=1.0×10⁻⁸, OR=0.59). The study replicated 10 previously established SLE risk loci (STAT4, TNFSF4, TNFAIP3, IKZF1, HIP1, IRF5, BLK, WDFY4, ETS1, IRAK1-MECP2) and identified novel independent effects in TNFAIP3 and TNFSF4. HLA-DRB1*1501 and HLA-DQB1*0602 were the strongest HLA associations (P=5.55×10⁻¹⁶, OR=1.85 and OR=1.90 respectively).

Traits studied:Systemic lupus erythematosus (SLE)
PubMedDOIMetascience Observatory
▶
Most common single‐nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans
AssociationN=1,347Hughes LB et al.(2010)· Arthritis &amp; Rheumatism

This study examined 27 previously identified rheumatoid arthritis (RA) risk alleles in 556 autoantibody-positive African-American RA cases and 791 controls. Twenty-four of 27 SNPs showed consistent odds ratios between African-Americans and Europeans; three SNPs (CCR6 rs3093023, TAGAP rs394581, TNFAIP3 rs6920220) showed opposite directions of effect. A genetic risk score analysis indicated that African-American cases were significantly enriched for European RA risk alleles (p=0.00005), suggesting that RA genetic risk factors are largely shared across ancestry groups.

Traits studied:Rheumatoid arthritis
PubMedDOIMetascience Observatory
▶
Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: Evidence of possible gene–gene interaction and alterations in Th1/Th2 cytokines
AssociationN=6,784Pravitt Gourh et al.(2009)· Arthritis &amp; Rheumatism

Two independent candidate gene association studies identified SNPs in TBX21 and STAT4 as significant risk factors for systemic sclerosis in North American whites. TBX21 rs11650354 (TT genotype) conferred 3.37-fold increased risk in recessive mode (P=1.4×10⁻¹⁵, combined N=902 cases/4,745 controls), while STAT4 rs11889341 A allele increased risk 1.29-fold in dominant mode (P=2.4×10⁻⁵, combined N=1,039 cases/3,322 controls). Gene-gene interaction analysis revealed synergistic effects on SSc susceptibility with altered Th1/Th2 cytokine profiles.

Traits studied:Systemic sclerosisSystemic sclerosis (diffuse cutaneous)Systemic sclerosis (limited cutaneous)Systemic sclerosis anti-RNA polymerase III antibody positiveSystemic sclerosis anti-topoisomerase I antibody positiveSystemic sclerosis anticentromere antibody positiveSystemic sclerosis with pulmonary fibrosis
PubMedDOIMetascience Observatory
▶
Association ofSTAT4with rheumatoid arthritis: A replication study in three European populations
AssociationN=4,546Gisela Orozco et al.(2008)· Arthritis &amp; Rheumatism

This multi-population case-control replication study examined the STAT4 polymorphism rs7574865 in 2,072 rheumatoid arthritis (RA) patients and 2,474 controls across Spain, Sweden, and The Netherlands. The T allele of rs7574865 showed significant association with RA risk with combined effect size OR 1.25 (95% CI 1.13-1.37, P = 9.79 × 10^-6). Meta-analysis across all published populations confirmed the association with OR 1.25 (95% CI 1.19-1.33, P = 1 × 10^-5).

Traits studied:Rheumatoid Arthritis
PubMedDOIMetascience Observatory

About STAT4

The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

View all STAT4 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Sign in to join the discussion.

Loading comments…