Gene: STAT3

Alternate names for this Gene: ADMIO|ADMIO1|APRF|HIES

Gene Summary: The protein encoded by this gene is a member of the STAT protein family. 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 activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Gene is located in Chromosome: 17

Location in Chromosome : 17q21.2

Description of this Gene: signal transducer and activator of transcription 3

Type of Gene: protein-coding

rs193922717 in STAT3 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1 PMID 25359994 2015 Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

PMID 25038750 2014 Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

PMID 28073828 2017 An Activating Mutation in STAT3 Results in Neonatal Diabetes Through Reduced Insulin Synthesis.

rs12942547 in STAT3 gene and Ankylosing spondylitis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs744166 in STAT3 gene and Asthma PMID 21150878 2011 Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia.

rs12942547 in STAT3 gene and Cholangitis, Sclerosing PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs12942547 in STAT3 gene and Crohn Disease PMID 26192919 2015 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

PMID 28067908 2017 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.

PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

PMID 18587394 2008 Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.

PMID 23266558 2013 We confirmed associations of Crohn's disease with variants in MHC (rs7765379, P = 2.11 × 10(-59)), TNFSF15 (rs6478106, P = 3.87 × 10(-45)), and STAT3 (rs9891119, P = 2.24 × 10(-14)).

rs17881320 in STAT3 gene and Dermatitis, Atopic PMID 26482879 2015 Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

rs17405722 in STAT3 gene and Diabetes Mellitus, Non-Insulin-Dependent PMID 30054458 2018 Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.

rs34846688 in STAT3 gene and Diastolic blood pressure PMID 30578418 2019 Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.

rs113994135 in STAT3 gene and HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT PMID 22581330 2012 STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway.

PMID 17881745 2007 STAT3 mutations in the hyper-IgE syndrome.

PMID 24452316 2014 Variable clinical expressivity of STAT3 mutation in hyperimmunoglobulin E syndrome: genetic and clinical studies of six patients.

PMID 21324546 2011 Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES).

PMID 17676033 2007 Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.

PMID 17942886 2007 STAT3 mutation in the original patient with Job's syndrome.

PMID 21792878 2011 SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function.

PMID 26384563 2015 The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters.

PMID 27799162 2016 Protein stabilization improves STAT3 function in autosomal dominant hyper-IgE syndrome.

PMID 18706697 2008 Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups.

PMID 18602572 2008 Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome.

PMID 22030463 2012 Heterozygous signal transducer and activator of transcription 3 mutations in hyper-IgE syndrome result in altered B-cell maturation.

PMID 23342295 2012 Signal transducer and activator of transcription 3 mutation with invasive eosinophilic disease.

PMID 23584561 2013 Lung parenchyma surgery in autosomal dominant hyper-IgE syndrome.

PMID 19577286 2009 Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

PMID 26293184 2016 Functional characterization of two new STAT3 mutations associated with hyper-IgE syndrome in a Mexican cohort.

PMID 22751495 2012 Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

PMID 25359994 2015 Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

PMID 25038750 2014 Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

PMID 20816194 2010 Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis.

PMID 29868029 2018 STAT3-Mediated Transcriptional Regulation of Osteopontin in STAT3 Loss-of-Function Related Hyper IgE Syndrome.

PMID 28315006 2017 Novel Mutation in SH2 Domain of STAT3 (p.M660T) in Hyper-IgE Syndrome with Sterno-Clavicular and Paravertebral Abscesses.

rs12942547 in STAT3 gene and Inflammatory Bowel Diseases PMID 23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

PMID 28067908 2017 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.

PMID 27569725 2016 Identification of Loci at 1q21 and 16q23 That Affect Susceptibility to Inflammatory Bowel Disease in Koreans.

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

rs113994139 in STAT3 gene and Job Syndrome PMID 21792878 2011 SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function.

PMID 20159255 2010 Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome.

PMID 20032313 2010 Uncovering an IL-10-dependent NF-kappaB recruitment to the IL-1ra promoter that is impaired in STAT3 functionally defective patients.

PMID 29077208 2018 Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics.

PMID 18706697 2008 Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups.

PMID 18602572 2008 Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome.

PMID 17881745 2007 STAT3 mutations in the hyper-IgE syndrome.

PMID 18978467 2008 Hyper IgE syndrome: an update on clinical aspects and the role of signal transducer and activator of transcription 3.

PMID 27980540 2016 Comprehensive genetic testing for primary immunodeficiency disorders in a tertiary hospital: 10-year experience in Auckland, New Zealand.

PMID 23584591 2013 Lipase-catalyzed acylation of microbial mannosylerythritol lipids (biosurfactants) and their characterization.

PMID 18591412 2008 Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells.

PMID 22751495 2012 Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

PMID 27226025 2016 TH17 Cells in STAT3 Related Hyper-IgE Syndrome.

PMID 20816194 2010 Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis.

rs1053004 in STAT3 gene and Mean Corpuscular Volume (result) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs2293152 in STAT3 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.

PMID 20159113 2010 SNP (rs744166) within the STAT3 gene was associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91).

PMID 21833088 2011 Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

rs1064794957 in STAT3 gene and Multiple congenital anomalies PMID 18602572 2008 Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome.

PMID 17881745 2007 STAT3 mutations in the hyper-IgE syndrome.

PMID 26394394 2015 54th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE). Barcelona, Spain, October 1-3, 2015: Abstracts.

PMID 28073828 2017 An Activating Mutation in STAT3 Results in Neonatal Diabetes Through Reduced Insulin Synthesis.

PMID 20159255 2010 Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome.

PMID 25038750 2014 Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

PMID 26343524 2015 A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation.

PMID 25359994 2015 Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

PMID 29180260 2018 A novel de novo activating mutation in STAT3 identified in a patient with common variable immunodeficiency (CVID).

PMID 22520845 2012 Inborn errors of human JAKs and STATs.

PMID 22751495 2012 Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

rs12942547 in STAT3 gene and Psoriasis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

rs113994135 in STAT3 gene and STAT3 Gain of Function PMID 22581330 2012 STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway.

PMID 17942886 2007 STAT3 mutation in the original patient with Job's syndrome.

PMID 21324546 2011 Clinical, immunological and genetic features in Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES).

PMID 17676033 2007 Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.

PMID 17881745 2007 STAT3 mutations in the hyper-IgE syndrome.

PMID 24452316 2014 Variable clinical expressivity of STAT3 mutation in hyperimmunoglobulin E syndrome: genetic and clinical studies of six patients.

PMID 26384563 2015 The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters.

PMID 18706697 2008 Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups.

PMID 21792878 2011 SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function.

PMID 27799162 2016 Protein stabilization improves STAT3 function in autosomal dominant hyper-IgE syndrome.

PMID 22030463 2012 Heterozygous signal transducer and activator of transcription 3 mutations in hyper-IgE syndrome result in altered B-cell maturation.

PMID 18602572 2008 Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome.

PMID 23584561 2013 Lung parenchyma surgery in autosomal dominant hyper-IgE syndrome.

PMID 19577286 2009 Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

PMID 22751495 2012 Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

PMID 25359994 2015 Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

PMID 25038750 2014 Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

PMID 29868029 2018 STAT3-Mediated Transcriptional Regulation of Osteopontin in STAT3 Loss-of-Function Related Hyper IgE Syndrome.

PMID 20816194 2010 Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis.

PMID 28315006 2017 Novel Mutation in SH2 Domain of STAT3 (p.M660T) in Hyper-IgE Syndrome with Sterno-Clavicular and Paravertebral Abscesses.

rs12942547 in STAT3 gene and Ulcerative Colitis PMID 26192919 2015 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

PMID 28067908 2017 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.