SH2B3

Overview

SH2B3 (also known as LNK) encodes an adapter protein that negatively regulates JAK2 signaling by binding to and inhibiting JAK2 kinase activity. Loss-of-function mutations in SH2B3 are recurrently observed in myeloproliferative neoplasms (MPN) and can collaborate with other driver mutations such as JAK2 V617F. SH2B3 acts as a tumor suppressor in the hematopoietic context, and its inactivation leads to enhanced cytokine-receptor signaling.

Alterations observed in the corpus

  • SH2B3 (LNK) somatic mutation identified in 1 MPN patient in an exome-sequencing cohort that discovered CALR as a recurrent MPN driver; found alongside other co-mutations in the myeloproliferative neoplasm context PMID:24325359
  • p.Tyr273* loss-of-function mutation in a JAK3-mutated Sézary syndrome case; acts as a negative regulator of JAK signaling PMID:26551667

Cancer types (linked)

  • MPN (myeloproliferative neoplasms): SH2B3 loss-of-function is a rare but recurrent somatic event in MPN, typically co-occurring with JAK2 or other myeloid driver mutations PMID:24325359

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • As a negative regulator of JAK2 signaling, SH2B3 loss-of-function may sensitize tumors to JAK inhibitors; no direct clinical data available from this corpus.

Open questions

  • The functional impact of specific SH2B3 somatic variants (missense vs. truncating) in MPN remains to be systematically characterized.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26551667

This page was processed by crosslinker on 2026-05-14.