NFKBIA
Overview
NFKBIA encodes IκBα, an inhibitor of NF-κB, which regulates the NF-κB signaling pathway by preventing the translocation of NF-κB to the nucleus. Mutations in NFKBIA can disrupt this regulation, leading to constitutive activation of NF-κB signaling, which has an important role in a subset of DLBCLs. Mutations and deletions in NFKBIA are observed in DLBCL and are associated with constitutive activation of the NF-κB pathway. These mutations often occur in the ABC subtype and are associated with the ST2 genetic subgroup of DLBCL.1
Relevance tier by entity
| Entity | Tier | Description |
|---|---|---|
 |
1 | high-confidence PMBL/cHL/GZL gene |
 |
1 | high-confidence DLBCL gene |
 |
2 | relevance in FL not firmly established |
Mutation incidence in large patient cohorts (GAMBL reanalysis)
| Entity | source | frequency (%) |
|---|---|---|
| DLBCL | GAMBL genomes | 4.40 |
| DLBCL | Schmitz cohort | 3.83 |
| DLBCL | Reddy cohort | 3.60 |
| DLBCL | Chapuy cohort | 4.70 |
| FL | GAMBL genomes | 0.69 |
Mutation pattern and selective pressure estimates
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | No | No | 3.358 | 17.442 |
| DLBCL | No | Yes | 9.385 | 40.878 |
| FL | No | No | 0.000 | 28.519 |
[!NOTE] First described in FL in 2023 by Russler-Germain DA
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
NFKBIA Expression
References
- Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551-568.e14. doi: 10.1016/j.ccell.2020.03.015. PMID: 32289277; PMCID: PMC8459709.
