NFKBIA

Overview

NFKBIA (IkBα) encodes the primary inhibitor of the NF-kB transcription factor family. By sequestering NF-kB dimers in the cytoplasm, NFKBIA acts as a tumor suppressor in B-cell lymphomas; loss-of-function mutations release constitutive NF-kB activity, which drives proliferation and survival.

Alterations observed in the corpus

  • NFKBIA somatic mutations were identified in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing of 55 tumors (Broad cohort), implicating NF-kB pathway dysregulation as a recurrent oncogenic mechanism PMID:22343534
  • NFKBIA copy-number gain (amplification) identified in recurrent GISTIC peaks in metastatic cSCC (n=29). PMID:25589618
  • Alterations in NFKBIA were associated with poorer prognosis specifically in GCB DLBCL (1001-patient cohort) PMID:28985567

Cancer types (linked)

  • DLBCL: somatic loss-of-function mutations; NF-kB pathway activation PMID:22343534

Co-occurrence and mutual exclusivity

  • Co-occurs with MYD88 mutations in the NF-kB pathway activation context in DLBCL PMID:22343534

Therapeutic relevance

  • NF-kB pathway (including NFKBIA loss and MYD88 gain-of-function) was highlighted as a targetable pathway in DLBCL PMID:22343534

Open questions

  • The relative contributions of NFKBIA loss versus MYD88 gain-of-function to NF-kB activation in individual DLBCL tumors remain to be fully characterized PMID:22343534

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15.