IKZF3 - morinlab/LLMPP GitHub Wiki
bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @paneaWholeGenomeLandscape2019, @lazarianHotspotMutationTranscription2021, @morinMutationalStructuralAnalysis2013,
Overview
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.[@lazarianHotspotMutationTranscription2021] While primarily studied in CLL, the functional effects of IKZF3 mutations could have implications for other B-cell malignancies, including DLBCL
Experimental Evidence
Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a gain of function (GOF).[@lazarianHotspotMutationTranscription2021]
Relevance tier by entity
include:tables/table1_IKZF3.md
Mutation incidence in large patient cohorts (GAMBL reanalysis)
DLBCL
BL
Mutation pattern and selective pressure estimates
aSHM regions
| chr_name | hg19_start | hg19_end | region | regulatory_comment |
|---|---|---|---|---|
| chr17 | 37928959 | 37940119 | TSS-1 | NA |
| chr17 | 38015776 | 38024832 | TSS-2 | NA |
IKZF3 Hotspots
| 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 |
include:tables/browser_IKZF3.md
Expression
include:tables/mermaid_IKZF3.md