JAK3
Overview
JAK3 (Janus Kinase 3) is a tyrosine kinase that mediates cytokine signalling through the JAK/STAT pathway, particularly via common gamma-chain cytokine receptors. In hepatocellular carcinoma (HCC), JAK3 is recurrently amplified and is among the FDA-targetable alterations in the JAK/STAT pathway.
Alterations observed in the corpus
- JAK3 recurrently amplified in HCC (243-case European WES cohort); listed as FDA-targetable at 3% frequency in the druggable landscape. PMID:25822088
- p.Val678Leu point mutation in a Sézary syndrome sample (previously reported in prolymphocytic leukemia); HUT78 CTCL cell line carries activating p.Ala573Val and responds to JAK inhibition with tofacitinib and ruxolitinib PMID:26551667
- JAK3 A573V activating mutation identified in pediatric AML as a JAK-inhibitor target in comprehensive clinical genomic sequencing PMID:28007021.
- Antigen-presentation/immunology gene profiled in OncoPrint alongside HLA-A, POLE, CD274, PTEN, and ATR in a 240-patient NSCLC immunotherapy cohort PMID:29337640
Cancer types (linked)
- HCC: Recurrent amplification at 3% frequency; FDA-targetable; part of JAK/STAT signalling axis in the 243-case European cohort. PMID:25822088
Co-occurrence and mutual exclusivity
Therapeutic relevance
- JAK3 amplification at 3% frequency is FDA-targetable in HCC; JAK inhibitors such as ruxolitinib are clinical candidates for JAK-amplified HCC. PMID:25822088
Open questions
- Whether JAK3 amplification drives STAT3 activation and represents an oncogenic dependency in HCC requires functional characterisation. PMID:25822088
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:26551667
This page was processed by crosslinker on 2026-05-14. - PMID:28007021
This page was processed by entity-page-writer on 2026-05-15. - PMID:29337640
This page was processed by wiki-cli on 2026-05-15.