Gene: SMAD3

Alternate names for this Gene: HSPC193|HsT17436|JV15-2|LDS1C|LDS3|MADH3

Gene Summary: The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. It also functions as a tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3.

Gene is located in Chromosome: 15

Location in Chromosome : 15q22.33

Description of this Gene: SMAD family member 3

Type of Gene: protein-coding

rs72743477 in SMAD3 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1 PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs72743477 in SMAD3 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 2 PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs72743477 in SMAD3 gene and AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 6 PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs56324967 in SMAD3 gene and Adenocarcinoma of large intestine PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56324967 in SMAD3 gene and Adenoma of large intestine PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56062135 in SMAD3 gene and Adult onset asthma PMID 31036433 2019 Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies.

PMID 30929738 2019 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

rs16950687 in SMAD3 gene and Allergic Reaction PMID 23817569 2013 A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.

PMID 27182965 2016 Detection and interpretation of shared genetic influences on 42 human traits.

PMID 29785011 2018 A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases.

PMID 29083406 2017 Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

rs17294280 in SMAD3 gene and Allergic rhinitis (disorder) PMID 30013184 2018 Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.

rs17293632 in SMAD3 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.

PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs10152595 in SMAD3 gene and Asthma PMID 31619474 2019 Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis.

PMID 30929738 2019 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

PMID 29273806 2018 Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

PMID 24388013 2014 Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

PMID 29785011 2018 A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases.

PMID 27182965 2016 Detection and interpretation of shared genetic influences on 42 human traits.

PMID 30552067 2019 Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.

PMID 22561531 2012 Genome-wide association study to identify genetic determinants of severe asthma.

PMID 20860503 2010 We observed associations of genomewide significance between asthma and the following single-nucleotide polymorphisms: rs3771166 on chromosome 2, implicating IL1RL1/IL18R1 (P=3×10(−9)); rs9273349 on chromosome 6, implicating HLA-DQ (P=7×10(−14)); rs1342326 on chromosome 9, flanking IL33 (P=9×10(−10)); rs744910 on chromosome 15 in SMAD3 (P=4×10(−9)); and rs2284033 on chromosome 22 in IL2RB (P=1.1×10(−8)).

PMID 21907864 2011 Identification of IL6R and chromosome 11q13.5 as risk loci for asthma.

rs72743477 in SMAD3 gene and Autoimmune Diseases PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs72743477 in SMAD3 gene and Autoimmune thyroiditis PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs2118611 in SMAD3 gene and Birth Weight PMID 31043758 2019 Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

rs2033784 in SMAD3 gene and Blood basophil count (lab test) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs35874463 in SMAD3 gene and Body Fat Distribution PMID 30664634 2019 Genome-wide association study of body fat distribution identifies adiposity loci and sex-specific genetic effects.

rs35874463 in SMAD3 gene and Body Height PMID 28552196 2017 Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 31562340 2019 Characterizing rare and low-frequency height-associated variants in the Japanese population.

rs56324967 in SMAD3 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 1 PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56324967 in SMAD3 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 10 PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56324967 in SMAD3 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 12 PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56324967 in SMAD3 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 3 PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs72743477 in SMAD3 gene and Celiac Disease PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs12912010 in SMAD3 gene and Central corneal thickness PMID 29760442 2018 Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

rs34445740 in SMAD3 gene and Childhood asthma PMID 30929738 2019 Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.

PMID 31036433 2019 Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies.

rs17293632 in SMAD3 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.

rs56324967 in SMAD3 gene and Colorectal Carcinoma PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56324967 in SMAD3 gene and Colorectal Neoplasms PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs72743477 in SMAD3 gene and Common Variable Immunodeficiency PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs12913547 in SMAD3 gene and Corneal Topography PMID 23291589 2013 Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

rs17228058 in SMAD3 gene and Coronary Artery Disease PMID 29212778 2018 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.

PMID 26343387 2015 A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

PMID 28714975 2017 Association analyses based on false discovery rate implicate new loci for coronary artery disease.

rs17228212 in SMAD3 gene and Coronary heart disease PMID 17634449 2007 The combined analysis of the two studies identified four additional loci significantly associated with coronary artery disease (P<1.3x10(-6)) and a high probability (>80%) of a true association: chromosomes 1p13.3 (rs599839), 1q41 (rs17465637), 10q11.21 (rs501120), and 15q22.33 (rs17228212).

PMID 21347282 2011 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

rs17293632 in SMAD3 gene and Crohn Disease PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

PMID 21102463 2010 Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

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

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

PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs72743477 in SMAD3 gene and Diabetes Mellitus, Insulin-Dependent PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs56375023 in SMAD3 gene and Eczema PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs17293632 in SMAD3 gene and Eosinophil count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs1566999423 in SMAD3 gene and Familial thoracic aortic aneurysm and aortic dissection PMID 30675029 2019 Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients.

PMID 21217753 2011 Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis.

PMID 25644172 2015 Gene panel sequencing in heritable thoracic aortic disorders and related entities - results of comprehensive testing in a cohort of 264 patients.

PMID 24804794 2014 Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

PMID 21778426 2011 Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms.

PMID 11779503 2001 Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.

PMID 10092624 1999 Cooperative binding of Smad proteins to two adjacent DNA elements in the plasminogen activator inhibitor-1 promoter mediates transforming growth factor beta-induced smad-dependent transcriptional activation.

PMID 20101697 2010 Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.

PMID 26854089 2016 Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing.

PMID 15235019 2004 The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations.

PMID 26133393 2016 Aortic dilation, genetic testing, and associated diagnoses.

PMID 25944730 2015 Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy.

rs11071939 in SMAD3 gene and Glomerular Filtration Rate PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.

rs17294280 in SMAD3 gene and Hay fever PMID 24388013 2014 Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

rs35874463 in SMAD3 gene and Height PMID 21194676 2011 Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.

rs17293632 in SMAD3 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.

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

rs72743477 in SMAD3 gene and Juvenile arthritis PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs387906850 in SMAD3 gene and LOEYS-DIETZ SYNDROME 3 PMID 21217753 2011 Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis.

PMID 21778426 2011 Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms.

PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 25173340 2014 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC).

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

rs72743477 in SMAD3 gene and Lupus Erythematosus, Systemic PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs56324967 in SMAD3 gene and Malignant neoplasm of large intestine PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs56324967 in SMAD3 gene and Malignant tumor of colon PMID 30510241 2019 Discovery of common and rare genetic risk variants for colorectal cancer.

rs72743461 in SMAD3 gene and Myocardial Infarction PMID 26343387 2015 A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

rs12901071 in SMAD3 gene and Osteoarthritis of hip PMID 30374069 2018 Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis.

PMID 30664745 2019 Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data.

rs17293632 in SMAD3 gene and Psoriasis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

PMID 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs72743481 in SMAD3 gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs11639295 in SMAD3 gene and Regular astigmatism - corneal PMID 30306274 2018 Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.

rs72743461 in SMAD3 gene and Respiratory Tract Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs2289261 in SMAD3 gene and Thyroid carcinoma PMID 28195142 2017 A genome-wide association study yields five novel thyroid cancer risk loci.

rs12912045 in SMAD3 gene and Tonometry PMID 29235454 2017 A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure.

PMID 29617998 2018 Genome-wide association analyses identify new loci influencing intraocular pressure.

rs4776342 in SMAD3 gene and Triglycerides measurement PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

rs17293632 in SMAD3 gene and Ulcerative Colitis PMID 26974007 2016 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

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 26301688 2015 Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

rs10438355 in SMAD3 gene and Vital capacity PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 30061609 2018 Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

rs10152595 in SMAD3 gene and Waist-Hip Ratio PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.