Gene: STAT4

Alternate names for this Gene: SLEB11

Gene Summary: 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.

Gene is located in Chromosome: 2

Location in Chromosome : 2q32.2-q32.3

Description of this Gene: signal transducer and activator of transcription 4

Type of Gene: protein-coding

rs7568275 in STAT4 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1 PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7568275 in STAT4 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 2 PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7568275 in STAT4 gene and AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 6 PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7568275 in STAT4 gene and Autoimmune Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 21383967 2011 Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

rs7572482 in STAT4 gene and Behcet Syndrome PMID 23001997 2012 Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome-wide association study.

PMID 23291587 2013 Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.

rs7574865 in STAT4 gene and Biliary cirrhosis PMID 23000144 2012 Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.

rs13401064 in STAT4 gene and Celiac Disease PMID 25920553 2016 Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci.

PMID 22057235 2011 Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease.

PMID 23143596 2012 High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

PMID 26546613 2016 Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis.

rs1517352 in STAT4 gene and Crohn Disease PMID 26192919 2015 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

rs10174238 in STAT4 gene and Eosinophil count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7582694 in STAT4 gene and Hypothyroidism PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7574865 in STAT4 gene and Immune System Diseases PMID 21383967 2011 Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

rs1517352 in STAT4 gene and Inflammatory Bowel Diseases PMID 23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

PMID 26192919 2015 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

rs13390936 in STAT4 gene and Invasive non-typhoidal salmonellosis PMID 29523850 2018 Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4.

rs10174238 in STAT4 gene and Juvenile pauciarticular chronic arthritis PMID 23603761 2013 Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

rs10174238 in STAT4 gene and Juvenile-Onset Still Disease PMID 23603761 2013 Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

rs10931481 in STAT4 gene and Liver carcinoma PMID 23242368 2013 Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.

PMID 23242368 2013 The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively).

rs10168266 in STAT4 gene and Lupus Erythematosus, Systemic PMID 23273568 2013 Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.

PMID 30573655 2019 Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.

PMID 21408207 2011 Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.

PMID 27399966 2016 Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus.

PMID 26606652 2016 Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.

PMID 26502338 2015 Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.

PMID 28714469 2017 Transancestral mapping and genetic load in systemic lupus erythematosus.

PMID 26663301 2016 Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans.

PMID 19165918 2008 Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus.

PMID 18204098 2008 Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.

PMID 21408207 2011 For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with p(heterogeneity)<0.0005.

PMID 18204446 2008 Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.

PMID 19838193 2009 Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.

PMID 24871463 2014 GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.

PMID 23053960 2012 Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis.

PMID 19838195 2009 A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.

PMID 26316170 2016 Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry.

PMID 23740937 2013 A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.

rs7574865 in STAT4 gene and Multiple Sclerosis PMID 22190364 2011 Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.

PMID 24076602 2013 Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.

rs10174238 in STAT4 gene and Myositis PMID 30573655 2019 Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.

rs10174238 in STAT4 gene and Oligoarticular Juvenile Idiopathic Arthritis PMID 23603761 2013 Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

rs11684030 in STAT4 gene and Oral Ulcer PMID 30837455 2019 Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci.

rs10174238 in STAT4 gene and Polyarticular Juvenile Idiopathic Arthritis, Rheumatoid Factor Negative PMID 23603761 2013 Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

rs10168266 in STAT4 gene and Primary biliary cirrhosis PMID 28425483 2017 A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.

PMID 22961000 2012 Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

PMID 22936693 2012 Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

PMID 23000144 2012 Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.

rs10168266 in STAT4 gene and Rheumatoid Arthritis PMID 23143596 2012 High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

PMID 23028356 2012 Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are associated with rheumatoid arthritis in Japanese.

PMID 30573655 2019 Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.

PMID 24390342 2014 Genetics of rheumatoid arthritis contributes to biology and drug discovery.

PMID 30423114 2019 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.

PMID 24532676 2015 High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.

PMID 26546613 2016 Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis.

PMID 20453842 2010 Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.

PMID 22446963 2012 Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.

rs10174238 in STAT4 gene and Rheumatoid Arthritis, Systemic Juvenile PMID 23603761 2013 Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

rs10174238 in STAT4 gene and Scleroderma, Limited PMID 29293537 2018 Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.

rs10168266 in STAT4 gene and Sjogren's Syndrome PMID 24097066 2013 A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.

PMID 24097067 2013 Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome.

PMID 28076899 2017 Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren's Syndrome According to Ancestry.

rs10174238 in STAT4 gene and Systemic Scleroderma PMID 29293537 2018 Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.

PMID 30573655 2019 Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.

PMID 24387989 2014 Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

PMID 21779181 2011 Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

PMID 20383147 2010 Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.

PMID 31672989 2019 GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways.

PMID 21750679 2011 Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.

PMID 28314753 2017 Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis.

PMID 23740937 2013 A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.

rs10174238 in STAT4 gene and Systemic onset juvenile chronic arthritis PMID 23603761 2013 Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

rs1517352 in STAT4 gene and Ulcerative Colitis PMID 26192919 2015 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

rs199559999 in STAT4 gene and Vitiligo PMID 27723757 2016 Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.