Summary of various effects of germline heterozygous IKZF1 mutations
| Functional test . | WT . | R213* (DD) . | S427* (DD) . | C467R (DD) . | R502L (DD) . | Y462* (del ZF5+6) . | R162Q (HI) . | N159S (DN) . |
|---|---|---|---|---|---|---|---|---|
| Dimerization | +++ | − | − | − | + | − | +++ | +++ |
| PC-HC (WT or mutant alone) | +++ | − | − | − | +++ | − | − | − |
| PC-HC (coexpression with WT) | ||||||||
| Mut-Mut | NA | − | − | − | +++ | − | − | − |
| WT-Mut | NA | − | − | − | +++ | − | ++ | − |
| WT-WT | +++ | ++ | ++ | ++ | +++ | ++ | ++ | − |
| DNA binding | ||||||||
| Monomer | +/++ | +++ | +++ | + | ++ | +++ | − | − |
| Multimer | +++ | − | − | + | + | − | − | − |
| Sumoylation | +++ | + | + | + | +++ | + | +++ | +++ |
| HDAC1 binding | + | +/− | +/− | +++ | ++ | +/− | + | + |
| Protein stability (CHX treated) | +++ | + | + | + | ++ | + | +++ | +++ |
| T/B/myeloid abnormalities | NA | T−/B++/M− | NA | T−/B+++/M− | T+++/B+++/M+++ | |||
| Infections | NA | −/+ | NA | +++ | +++ | |||
| Autoimmune cytopenias | NA | ++/+++ | NA | + | − | |||
| Hematologic malignancies | NA | ++/+++ | NA | + | +/++ | |||
| Functional test . | WT . | R213* (DD) . | S427* (DD) . | C467R (DD) . | R502L (DD) . | Y462* (del ZF5+6) . | R162Q (HI) . | N159S (DN) . |
|---|---|---|---|---|---|---|---|---|
| Dimerization | +++ | − | − | − | + | − | +++ | +++ |
| PC-HC (WT or mutant alone) | +++ | − | − | − | +++ | − | − | − |
| PC-HC (coexpression with WT) | ||||||||
| Mut-Mut | NA | − | − | − | +++ | − | − | − |
| WT-Mut | NA | − | − | − | +++ | − | ++ | − |
| WT-WT | +++ | ++ | ++ | ++ | +++ | ++ | ++ | − |
| DNA binding | ||||||||
| Monomer | +/++ | +++ | +++ | + | ++ | +++ | − | − |
| Multimer | +++ | − | − | + | + | − | − | − |
| Sumoylation | +++ | + | + | + | +++ | + | +++ | +++ |
| HDAC1 binding | + | +/− | +/− | +++ | ++ | +/− | + | + |
| Protein stability (CHX treated) | +++ | + | + | + | ++ | + | +++ | +++ |
| T/B/myeloid abnormalities | NA | T−/B++/M− | NA | T−/B+++/M− | T+++/B+++/M+++ | |||
| Infections | NA | −/+ | NA | +++ | +++ | |||
| Autoimmune cytopenias | NA | ++/+++ | NA | + | − | |||
| Hematologic malignancies | NA | ++/+++ | NA | + | +/++ | |||
All mutations, with the exception of Y462* (a laboratory-generated mutant to test the effect of deletion of ZF5 and ZF6), were found in patients. R162Q and N159S are previously reported DNA binding–defective IKZF1 mutations acting by HI or DN effect, respectively. +/++/+++ indicates the strength of each IKAROS function test; +++ is the strongest; and − is not detected (all vs WT).
CHX, cycloheximide; NA, not applicable.