4 SH2B3
4.1 Function and mutations
- Adapter protein with SH2 and PH domains.
- Negatively regulates JAK2 at cytokine receptors (TPO, EPO, IL-3) — physiological brake on megakaryopoiesis and erythropoiesis.
LOF SH2B3→ uncoupled JAK2 → constitutive JAK-STAT activation → cytokine-independent megakaryocyte expansion