IKZF3 - morinlab/LLMPP GitHub Wiki
IKZF3 (IKAROS family zinc finger 3, also known as AIOLOS) is a transcription factor involved in regulating B-cell development and function. Mutations in IKZF3 can lead to transcriptional dysregulation and contribute to the pathogenesis of B-cell neoplasms. IKZF3 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. IKZF3 has multiple hot spot mutations in DLBCL. The most common, L162R, has been identified as a driver in CLL. In that context, it alters DNA binding specificity and causes hyperactivation of B-cell receptor (BCR) signaling and overexpression of NF-κB target genes.1 While primarily studied in CLL, the functional effects of IKZF3 mutations could have implications for other B-cell malignancies, including DLBCL
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timeline
title Publication timing
2013-08-15 : Morin : DLBCL
2019-09-26 : Panea : BL
| Entity | Tier | Description |
|---|---|---|
 |
2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@paneaWholeGenomeLandscape2019] |
 |
1-a | aSHM target and high-confidence DLBCL gene [@morinMutationalStructuralAnalysis2013] |
| Entity | source | frequency (%) |
|---|---|---|
| BL | GAMBL genomes+capture | 1.62 |
| BL | Thomas cohort | 0.80 |
| BL | Panea cohort | 3.00 |
| DLBCL | GAMBL genomes | 4.78 |
| DLBCL | Schmitz cohort | 4.47 |
| DLBCL | Reddy cohort | 3.90 |
| DLBCL | Chapuy cohort | 4.27 |
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | Yes | No | 1.552 | 0 |
| DLBCL | Yes | No | 10.924 | 0 |
| FL | Yes | No | 7.180 | 0 |
| chr_name | hg19_start | hg19_end | region | regulatory_comment |
|---|---|---|---|---|
| chr17 | 37928959 | 37940119 | TSS-1 | NA |
| chr17 | 38015776 | 38024832 | TSS-2 | NA |
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr17 | 37948968 | T>C | I128V |
| chr17 | 37948958 | T>C | N131S |
| chr17 | 37948950 | T>C | M134V |
| chr17 | 37948949 | A>T | M134K |
| chr17 | 37947783 | T>G | N160H |
| chr17 | 37947782 | T>C | N160S |
| chr17 | 37947776 | A>C | L162R |
| chr17 | 37944583 | G>T | Q213K |
| chr17 | 37944582 | T>C | Q213R |
| chr17 | 37944577 | T>G | S215R |
| chr17 | 37944575 | A>T | S215R |
| chr17 | 37944575 | A>C | S215R |
| chr17 | 37944568 | C>T | E218K |
| chr17 | 37944565 | C>T | E219K |
| chr17 | 37944564 | T>A | E219V |
| chr17 | 37944556 | C>T | E222K |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
- Lazarian, G., Yin, S., Hacken, E., Sewastianik, T., Uduman, M., Font-Tello, A., Gohil, S., Li, S., Kim, E., Joyal, H., Billington, L., Witten, E., Zheng, M., Huang, T., Severgnini, M., Lefebvre, V., Rassenti, L., Gutierrez, C., Georgopoulos, K., Ott, C., Wang, L., Kipps, T., Burger, J., Livak, K., Neuberg, D., Baran-Marszak, F., Cymbalista, F., Carrasco, R., & Wu, C. (2021). A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation.. Cancer cell, 39 3, 380-393.e8 . https://doi.org/10.1016/j.ccell.2021.02.003.
