STAT6

Table of Contents

Overview

The STAT6 gene, which encodes a transcription factor involved in the JAK-STAT signaling pathway, plays a significant role in the pathogenesis of various lymphomas, including diffuse large B-cell lymphoma (DLBCL). Below is a summary of the common mutations in the STAT6 gene identified in DLBCL. Mutations in the DNA binding domain of STAT6 are common in PMBCL and more rare in DLBCL.

Experimental Evidence

Driver mutations affecting this gene in DLBCL/FL have been experimentally demonstrated to cause a gain of function (GOF).1

Relevance tier by entity

Cannot include /table1_STAT6.md - does not exist yet

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Cannot include /DLBCL_STAT6.md - does not exist yet

Cannot include /FL_STAT6.md - does not exist yet

Mutation pattern and selective pressure estimates

Cannot include /dnds_STAT6.md - does not exist yet

STAT6 Hotspots

Recurrent mutations at the D419 amino acid residue are a common feature in DLBCL, specifically affecting the germinal center B (GCB) cell subtype. These mutations lead to the activation of the JAK/STAT signaling pathway, contributing to lymphomagenesis2.

Chromosome Coordinate (hg19) ref>alt HGVSp
chr12 57496671 C>G G416R
chr12 57496666 G>T N417K
chr12 57496662 C>T D419N
chr12 57496662 C>G D419H
chr12 57496662 C>A D419Y
chr12 57496661 T>G D419A
chr12 57496661 T>C D419G
chr12 57496661 T>A D419V
chr12 57496658 T>G N420T
chr12 57496658 T>C N420S
chr12 57496656 T>C N421D
chr12 57496654 A>C N421K

Cannot include /browser_STAT6.md - does not exist yet

Expression

Cannot include /mermaid_STAT6.md - does not exist yet

References

1.
Mentz M, Keay W, Strobl CD, Antoniolli M, Adolph L, Heide M, Lechner A, Haebe S, Osterode E, Kridel R, Ziegenhain C, Wange LE, Hildebrand JA, Shree T, Silkenstedt E, Staiger AM, Ott G, Horn H, Szczepanowski M, Richter J, Levy R, Rosenwald A, Enard W, Zimber-Strobl U, von Bergwelt-Baildon M, Hiddemann W, Klapper W, Schmidt-Supprian M, Rudelius M, Bararia D, Passerini V, Weigert O. PARP14 is a novel target in STAT6 mutant follicular lymphoma. Leukemia. 2022 Sep;36(9):2281–2292. PMCID: PMC9417990
2.
Morin RD, Assouline S, Alcaide M, Mohajeri A, Johnston RL, Chong L, Grewal J, Yu S, Fornika D, Bushell K, Nielsen TH, Petrogiannis-Haliotis T, Crump M, Tosikyan A, Grande BM, MacDonald D, Rousseau C, Bayat M, Sesques P, Froment R, Albuquerque M, Monczak Y, Oros KK, Greenwood C, Riazalhosseini Y, Arseneault M, Camlioglu E, Constantin A, Pan-Hammarstrom Q, Peng R, Mann KK, Johnson NA. Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas. Clin Cancer Res. 2016 May 1;22(9):2290–2300.
3.
Ritz O, Guiter C, Castellano F, Dorsch K, Melzner J, Jais JP, Dubois G, Gaulard P, Möller P, Leroy K. Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma. Blood. 2009 Aug 6;114(6):1236–1242. PMCID: PMC2824656
4.
Yildiz M, Li H, Bernard D, Amin NA, Ouillette P, Jones S, Saiya-Cork K, Parkin B, Jacobi K, Shedden K, Wang S, Chang AE, Kaminski MS, Malek SN. Activating STAT6 mutations in follicular lymphoma. Blood. 2015 Jan 22;125(4):668–679. PMCID: PMC4729538

Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

Disclaimer

The content in these pages has been populated, in part, by an automated process. Although we have scrutinized every page to ensure accuracy, errors will inevitably exist. If you find an error please report it as an issue and we will address it.

License

This work is licensed under a Creative Commons Attribution 4.0 International License.

You are free to:

Share — copy and redistribute the material in any medium or format for any purpose, even commercially.

Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms.