{"entity":{"id":"ikzf1","kind":"target","name":"IKZF1 (Ikaros)","aka":["Ikaros","IKAROS","ZNFN1A1","IKAROS family zinc finger 1"],"tldr":"Ikaros is a transcription factor that myeloma cells depend on. Lenalidomide, pomalidomide and the newer CELMoDs work by gluing Ikaros to the cell's disposal machinery so it is destroyed, which kills the plasma cell and wakes up T cells.","summary":"IKZF1 (chromosome 7p12.2) encodes Ikaros, a zinc-finger transcription regulator of haematopoietic differentiation and B- and T-lymphocyte development that binds gamma-satellite DNA, activates the CD3-delta enhancer, represses TDT during thymocyte differentiation, and regulates transcription through HDAC-dependent and independent complexes and the NuRD and BAF chromatin remodellers; dominant-negative isoforms modulate its function (UniProt Q13422). In OnCo it is the neosubstrate that thalidomide, lenalidomide and pomalidomide recruit to cereblon for ubiquitination and proteasomal degradation, and that golcadomide, a cereblon E3 ligase modulator, degrades alongside Aiolos; the loss lowers IRF4 and MYC in myeloma cells and stimulates T cells.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:13176","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13176"},{"label":"UniProt Q13422","url":"https://www.uniprot.org/uniprotkb/Q13422/entry"},{"label":"NCBI Gene 10320","url":"https://www.ncbi.nlm.nih.gov/gene/10320"}],"tags":["wave5-target"],"related":["cereblon","ikzf3","irf4","myc"],"cancers":["multiple-myeloma","dlbcl"],"sections":[],"technologies":["celmods","molecular-glue-platforms"],"targets":[],"drugs":["lenalidomide","pomalidomide","thalidomide","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":"IKZF1","hgnc":"HGNC:13176","ensembl":"ENSG00000185811","uniprot":"Q13422","entrez":"10320","biology":"Ikaros is degraded rather than inhibited: the immunomodulatory drugs bind cereblon in the CRL4 ubiquitin ligase and change its substrate preference so that Ikaros and Aiolos are ubiquitinated and destroyed (lenalidomide mechanism steps). The lenalidomide record calls this the basis for CELMoDs and molecular-glue degraders generally.","whereFound":["Multiple myeloma (degradation by immunomodulatory drugs and CELMoDs)","Diffuse large B-cell lymphoma (lenalidomide; golcadomide trials)","Kaposi sarcoma (pomalidomide)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/ikzf1/","neighbours":{"target":[{"id":"cereblon","kind":"target","name":"Cereblon (CRBN)","route":"/targets/cereblon/"},{"id":"ikzf3","kind":"target","name":"IKZF3 (Aiolos)","route":"/targets/ikzf3/"},{"id":"irf4","kind":"target","name":"IRF4","route":"/targets/irf4/"}],"pathway":[{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"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/"}],"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/"}],"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/"},{"id":"thalidomide","kind":"drug","name":"Thalidomide","route":"/drugs/thalidomide/"}]}}