{"entity":{"id":"ikzf3","kind":"target","name":"IKZF3 (Aiolos)","aka":["Aiolos","ZNFN1A3","IKAROS family zinc finger 3"],"tldr":"Aiolos is Ikaros' partner transcription factor in B cells and plasma cells. The myeloma drugs lenalidomide, pomalidomide and golcadomide destroy Aiolos and Ikaros together by rerouting them to the cell's protein-disposal system.","summary":"IKZF3 (chromosome 17q12-q21.1) encodes Aiolos, a transcription factor that regulates lymphocyte differentiation and is essential for B-cell differentiation, proliferation and maturation to an effector state; it regulates BCL2 expression and controls IL-2-dependent apoptosis in T cells (UniProt Q9UKT9). In OnCo it is the second cereblon neosubstrate, alongside Ikaros, that lenalidomide and pomalidomide recruit for ubiquitination and proteasomal degradation and that golcadomide degrades; the loss lowers IRF4 and MYC in myeloma cells and stimulates T and NK cells.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:13178","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13178"},{"label":"UniProt Q9UKT9","url":"https://www.uniprot.org/uniprotkb/Q9UKT9/entry"},{"label":"NCBI Gene 22806","url":"https://www.ncbi.nlm.nih.gov/gene/22806"}],"tags":["wave5-target"],"related":["cereblon","ikzf1","irf4","bcl2"],"cancers":["multiple-myeloma","myeloma-relapsed-refractory","dlbcl"],"sections":[],"technologies":["celmods","molecular-glue-platforms"],"targets":[],"drugs":["lenalidomide","pomalidomide","golcadomide"],"companies":[],"institutions":[],"pathways":["ubiquitin-proteasome-system","transcription-addiction"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"IKZF3","hgnc":"HGNC:13178","ensembl":"ENSG00000161405","uniprot":"Q9UKT9","entrez":"22806","biology":"Aiolos and Ikaros are destroyed by the same molecular-glue mechanism: the drug binds cereblon in the CRL4 ligase, the complex gains affinity for both transcription factors, and both are ubiquitinated (lenalidomide mechanism steps). Pomalidomide keeps this activity after lenalidomide failure.","whereFound":["Multiple myeloma (degradation by immunomodulatory drugs and CELMoDs)","Diffuse large B-cell lymphoma (golcadomide trials)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/ikzf3/","neighbours":{"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"cereblon","kind":"target","name":"Cereblon (CRBN)","route":"/targets/cereblon/"},{"id":"ikzf1","kind":"target","name":"IKZF1 (Ikaros)","route":"/targets/ikzf1/"},{"id":"irf4","kind":"target","name":"IRF4","route":"/targets/irf4/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"technology":[{"id":"celmods","kind":"technology","name":"Cereblon E3 ligase modulators (CELMoDs)","route":"/technologies/celmods/"},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","route":"/technologies/molecular-glue-platforms/"}],"drug":[{"id":"golcadomide","kind":"drug","name":"Golcadomide","route":"/drugs/golcadomide/"},{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"},{"id":"pomalidomide","kind":"drug","name":"Pomalidomide","route":"/drugs/pomalidomide/"}],"pathway":[{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"},{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}]}}