TIFAB Gene - Function, Mutations, and Role in Myeloid Neoplasms

TIFAB (TRAF-Interacting Protein with Forkhead-Associated Domain B) encodes a protein containing a forkhead-associated (FHA) domain that interacts with TRAF6, a key adaptor in Toll-like receptor and interleukin-1 receptor signaling. TIFAB negatively regulates TRAF6 ubiquitination and downstream NF-κB activation, thereby modulating innate immune responses. The gene is located on chromosome 5q31.1, a region frequently deleted in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), suggesting a tumor suppressor role. Loss of TIFAB expression in hematopoietic cells impairs p53 signaling and enhances susceptibility to malignant transformation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Toll-like receptor signaling pathway (KEGG hsa04620)

• IL-1 signaling pathway (Reactome R-HSA-446652)

• TRAF6-mediated NF-κB activation (Reactome R-HSA-933542)

TIFAB is a 184-amino acid protein containing an N-terminal FHA domain that mediates interaction with TRAF6. It localizes to both cytoplasm and nucleus. By binding TRAF6, TIFAB inhibits TRAF6 autoubiquitination and subsequent NF-κB activation, acting as a negative feedback regulator of innate immune signaling. In hematopoietic cells, TIFAB loss leads to p53 dysfunction and increased susceptibility to DNA damage, contributing to the pathogenesis of del(5q) myeloid neoplasms.