The STAT4 gene provides instructions for a protein that acts as a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. The STAT4 protein is turned on (activated) by immune system proteins called cytokines, which are part of the inflammatory response to fight infection. When activated, the STAT4 protein increases the activity of genes that help immune cells called T-cells mature into specialized T-cells. These specialized T-cells, called Th1 cells, produce specific cytokines and stimulate other immune cells to get rid of foreign invaders (pathogens) in the cell.
Health Conditions Related to Genetic Changes
A normal variation in the STAT4 gene has been associated with an increased risk of developing systemic scleroderma, which is an autoimmune disorder characterized by the buildup of scar tissue (fibrosis) in the skin and internal organs. Although the STAT4 gene is known to stimulate the immune system in response to pathogens, it is unknown how the gene variation contributes to the increased risk of systemic scleroderma. Researchers believe that a combination of genetic and environmental factors may play a role in development of the condition.More About This Health Condition
Juvenile idiopathic arthritis
MedlinePlus Genetics provides information about Juvenile idiopathic arthritisMore About This Health Condition
MedlinePlus Genetics provides information about Rheumatoid arthritisMore About This Health Condition
Systemic lupus erythematosus
MedlinePlus Genetics provides information about Systemic lupus erythematosusMore About This Health Condition
Studies have associated a normal variation in the STAT4 gene with an increased risk of several autoimmune disorders. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. These disorders include systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome.
The variant associated with increased risk of autoimmune disorders changes a single DNA building block (nucleotide) in the STAT4 gene. It is unknown how the gene variation contributes to increased risk of these conditions. Researchers believe that a combination of genetic and environmental factors may play a role in development of autoimmunity.
Other Names for This Gene
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Allanore Y, Dieude P, Boileau C. Updating the genetics of systemic sclerosis. Curr Opin Rheumatol. 2010 Nov;22(6):665-70. doi: 10.1097/BOR.0b013e32833d110a. Citation on PubMed
- Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, Coenen MJ, Vonk MC, Voskuyl AE, Schuerwegh AJ, Broen JC, van Riel PL, van 't Slot R, Italiaander A, Ophoff RA, Riemekasten G, Hunzelmann N, Simeon CP, Ortego-Centeno N, Gonzalez-Gay MA, Gonzalez-Escribano MF; Spanish Scleroderma Group, Airo P, van Laar J, Herrick A, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, Kiener H, de Baere E, Witte T, Padykov L, Klareskog L, Beretta L, Scorza R, Lie BA, Hoffmann-Vold AM, Carreira P, Varga J, Hinchcliff M, Gregersen PK, Lee AT, Ying J, Han Y, Weng SF, Amos CI, Wigley FM, Hummers L, Nelson JL, Agarwal SK, Assassi S, Gourh P, Tan FK, Koeleman BP, Arnett FC, Martin J, Mayes MD. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010 May;42(5):426-9. doi: 10.1038/ng.565. Epub 2010 Apr 11. Citation on PubMed or Free article on PubMed Central
- Rueda B, Broen J, Simeon C, Hesselstrand R, Diaz B, Suarez H, Ortego-Centeno N, Riemekasten G, Fonollosa V, Vonk MC, van den Hoogen FH, Sanchez-Roman J, Aguirre-Zamorano MA, Garcia-Portales R, Pros A, Camps MT, Gonzalez-Gay MA, Coenen MJ, Airo P, Beretta L, Scorza R, van Laar J, Gonzalez-Escribano MF, Nelson JL, Radstake TR, Martin J. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum Mol Genet. 2009 Jun 1;18(11):2071-7. doi: 10.1093/hmg/ddp119. Epub 2009 Mar 13. Citation on PubMed
- Thieu VT, Yu Q, Chang HC, Yeh N, Nguyen ET, Sehra S, Kaplan MH. Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination. Immunity. 2008 Nov 14;29(5):679-90. doi: 10.1016/j.immuni.2008.08.017. Citation on PubMed or Free article on PubMed Central
- Watford WT, Hissong BD, Bream JH, Kanno Y, Muul L, O'Shea JJ. Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev. 2004 Dec;202:139-56. doi: 10.1111/j.0105-2896.2004.00211.x. Citation on PubMed