IKZF3

Summary

IKZF3 (IKAROS family zinc finger 3, HGNC:13178) is a protein-coding gene on chromosome 17q12-q21.1, encoding Zinc finger protein Aiolos (Q9UKT9). Transcription factor that plays an important role in the regulation of lymphocyte differentiation.

This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this protein family (Ikaros, Aiolos and Helios) are hematopoietic-specific transcription factors involved in the regulation of lymphocyte development. This gene product is a transcription factor that is important in the regulation of B lymphocyte proliferation and differentiation. Both Ikaros and Aiolos can participate in chromatin remodeling. Regulation of gene expression in B lymphocytes by Aiolos is complex as it appears to require the sequential formation of Ikaros homodimers, Ikaros/Aiolos heterodimers, and Aiolos homodimers. Several alternative transcripts encoding different isoforms have been described, as well as some non-protein coding variants.

Source: NCBI Gene 22806 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 84 (Strong, GenCC)
• GWAS associations: 64
• Clinical variants (ClinVar): 79 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_012481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13178
Approved symbol	IKZF3
Name	IKAROS family zinc finger 3
Location	17q12-q21.1
Locus type	gene with protein product
Status	Approved
Aliases	Aiolos
Ensembl gene	ENSG00000161405
Ensembl biotype	protein_coding
OMIM	606221
Entrez	22806

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 nonsense_mediated_decay

ENST00000293068, ENST00000346243, ENST00000346872, ENST00000348427, ENST00000350532, ENST00000351680, ENST00000377944, ENST00000377945, ENST00000377952, ENST00000377958, ENST00000394189, ENST00000439016, ENST00000439167, ENST00000467757, ENST00000535189, ENST00000583368, ENST00000623724

RefSeq mRNA: 16 — MANE Select: NM_012481 NM_001257408, NM_001257409, NM_001257410, NM_001257411, NM_001257412, NM_001257413, NM_001257414, NM_001284514, NM_001284515, NM_001284516, NM_012481, NM_183228, NM_183229, NM_183230, NM_183231, NM_183232

CCDS: CCDS11346, CCDS11347, CCDS11348, CCDS11349, CCDS11350, CCDS11351, CCDS58539, CCDS58540, CCDS58541, CCDS58542, CCDS58543, CCDS58544, CCDS58545, CCDS74055

Canonical transcript exons

ENST00000346872 — 8 exons

Exon	Start	End
ENSE00001845780	39757718	39766493
ENSE00002346548	39788258	39788374
ENSE00002379824	39791416	39791583
ENSE00002381797	39829387	39829488
ENSE00002390397	39792673	39792933
ENSE00002397329	39832098	39832151
ENSE00003628965	39777651	39777767
ENSE00003841233	39864120	39864312

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 89.94.

FANTOM5 (CAGE): breadth broad, TPM avg 10.1758 / max 360.2374, expressed in 405 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165641	3.8455	309
165633	1.5097	142
165644	1.2627	162
165630	0.9172	117
165643	0.7248	131
165642	0.4552	116
165632	0.3995	93
165645	0.2986	99
165629	0.2280	82
165631	0.1078	61

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	89.94	gold quality
lymph node	UBERON:0000029	89.90	gold quality
epithelium of nasopharynx	UBERON:0001951	89.22	gold quality
nasopharynx	UBERON:0001728	89.20	gold quality
ileal mucosa	UBERON:0000331	88.76	silver quality
bone marrow cell	CL:0002092	87.25	gold quality
thymus	UBERON:0002370	85.81	gold quality
spleen	UBERON:0002106	85.41	gold quality
blood	UBERON:0000178	83.28	gold quality
tonsil	UBERON:0002372	82.96	gold quality
superficial temporal artery	UBERON:0001614	80.54	gold quality
vermiform appendix	UBERON:0001154	79.99	gold quality
caecum	UBERON:0001153	77.83	gold quality
bone marrow	UBERON:0002371	77.55	gold quality
colonic epithelium	UBERON:0000397	76.62	gold quality
buccal mucosa cell	CL:0002336	75.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.43	gold quality
amniotic fluid	UBERON:0000173	73.22	gold quality
small intestine	UBERON:0002108	72.77	gold quality
jejunal mucosa	UBERON:0000399	72.01	gold quality
rectum	UBERON:0001052	70.46	gold quality
gall bladder	UBERON:0002110	70.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.00	gold quality
oral cavity	UBERON:0000167	69.26	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.11	gold quality
mucosa of transverse colon	UBERON:0004991	68.98	gold quality
palpebral conjunctiva	UBERON:0001812	68.47	gold quality
duodenum	UBERON:0002114	68.36	gold quality
left ventricle myocardium	UBERON:0006566	68.09	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	1590.10
E-MTAB-6678	yes	656.88
E-MTAB-9067	yes	281.93
E-MTAB-8142	yes	40.07
E-ANND-3	yes	19.58
E-HCAD-9	yes	17.47
E-CURD-122	yes	13.12
E-CURD-112	yes	9.94
E-MTAB-8410	yes	9.32
E-GEOD-36552	no	20.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
AICDA	Unknown
BCL2	Unknown
IGLL1	Repression
IL2	Activation
LNPEP	Activation
MYC	Repression

Upstream regulators (CollecTRI, top): IKZF1, NFKB, RUNX1, TFAP4

miRNA regulators (miRDB)

316 targeting IKZF3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7G-5P	99.98	72.37	1784

Literature-anchored findings (GeneRIF, showing 40)

• Short isoforms of Aiolos were detected at low levels in bone marrow of normal volunters, but were not overexpressed in a patient with acute T-cell leukemia. Data for unaltered Aiolos indicates tumor suppressor function. (PMID:11937265)
• Aiolos knockout mice develop the symptoms of human systemic lupus erythematosus (SLE). This finding implicates Aiolos as a possible candidate gene for SLE. (PMID:12574333)
• impairment of Aiolos activity in human leukemia is not based on deficient phosphorylation as had been demonstrated in experiments in vitro (PMID:17296582)
• Retardation gels showed binding activity for Ikaros, NFkappaB and AP4 transcription factors and mutations in their binding sites abolish Aiolos promoter activity. (PMID:17383641)
• this work demonstrates that the cellular activities of Aiolos isoforms are dependent on combinations of various functional domains arising from the differential splicing of mRNA transcripts (PMID:17646674)
• up-regulation of Aiolos, confirmed at protein level, seems independent of Aiolos promoter H3K9 acetylation and H3K4 trimethylation (PMID:18184862)
• DNA methylation directs Aiolos silencing and chromatin status in tumor cell lines, while in primary cells is mainly regulated by histone modifications. (PMID:18206652)
• showed Aiolos overexpression in primary lymphoma tissue (PMID:18332232)
• we show for the first time the differential Aiolos expression at the RNA and protein level in hematopoietic cell subpopulations. (PMID:19540588)
• distribution of positive and negative expression of Aiolos and Helios found in various types of leukemias could implicate common pathways of their regulation (PMID:20432734)
• To determine the consequences of Aiolos deregulation in B-CLL, we analyzed the effects of Aiolos overexpression or down-regulation on apoptosis. (PMID:21139082)
• Four additional susceptibility loci (IRF8, TMEM39A, IKZF3, and ZPBP2) for systemic lupus erythematosus were robustly established a multiethnic population (European, African American, Asian, Hispanic, Gullah, and Amerindian). (PMID:22464253)
• Sixteen SNPs were significantly associated with asthma of which one SNP was novel (IKZF3-rs1453559). (PMID:22626592)
• Overexpression of AIOLOS inhibits cell proliferation, suppresses apoptosis and arrests the cell cycle at the G0/G1 phase in vitro. (PMID:24399134)
• A strong allelic association between SNPs in the 17q21 region (IKZF3) and asthma has been confirmed for the Latinos population. (PMID:24406073)
• Aiolos reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66(Shc) and blocking anoikis in vitro and in vivo. (PMID:24823637)
• NFKB1, CD27, LAG3 and IKZF3 are new susceptibility genes for psoriasis. (PMID:25006012)
• A strong association between rs907091 in the IKZF3 gene and SLE was identified. (PMID:25271777)
• The immunosuppressive enzyme IL4I1 expressed differentially in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells. (PMID:25446972)
• lentivirus-mediated AIOLOS overexpression in Jurkat cells induced cell apoptosis, arrested the cell cycle at the G0/G1 phase, and synergistically increased the sensitivity of Jurkat cells to etoposide by inhibiting NF-kappaB activity. (PMID:25524659)
• Aiolos improved the survival of Nalm6 cells via PTEN and Aktdependent processes. (PMID:25608224)
• The allele T of rs10852936 surrounding the IKZF3-ZPBP2 locus confers risk for early-onset psoriasis. (PMID:25620289)
• identified a unique case of adult acute B-cell lymphoblastic leukemia with masked low hypodiploidy (mLH) by genomic duplication (PMID:26185311)
• results indicate that overexpression of Aiolos may contribute to pathogenesis of SLE and RA (PMID:26546109)
• Aiolos promotes the binding of Blimp-1 to target genes and thereby enhances Blimp-1-dependent transcriptional repression. (PMID:26823144)
• Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. (PMID:27080863)
• this study shows that Ikaros undergoes a transient increase in protein levels at the transitional single-positive CD8+ developmental stage before diverging in their expression patterns at later stages (PMID:27502439)
• IKZF1 and IKZF3 expressions were associated with longer median progression free survival and overall survival in multiple myeloma patients (PMID:27881177)
• Inhibition of B cell plasmablast differentiation by reduction of Aiolos and Ikaros may have utility in the treatment of systemic lupus erythematosus , where elevated levels of BAFF and Aiolos may prime CD27(+) memory and double negative memory-like B cells to become Ab-producing plasmablasts in the presence of BAFF and proinflammatory cytokines. (PMID:28848067)
• The minor alleles of rs2941522, rs907091, rs1453559, rs12150079 and rs2872507 were statistically associated with an increased risk in Graves’ disease patients. (PMID:29510406)
• we identified and characterised oncogenic fusion genes and their function in CRC, and implicated NAGLU-IKZF3 and RNF121-FOLR2 as novel molecular targets for personalised medicine development. (PMID:29955133)
• Overexpression of Aiolos promotes epithelial-mesenchymal transition and cancer stem cell-like properties in lung cancer cells. (PMID:30816208)
• Selective degradation of Aiolos and Ikaros (IKZF1) by lenalidomide suppressed ILC1 and NK cell differentiation. (PMID:31151137)
• IKZF1/3 and CRL4(CRBN) E3 ubiquitin ligase mutations and resistance to immunomodulatory drugs in multiple myeloma. (PMID:31558666)
• Trans-Ancestral Fine-Mapping and Epigenetic Annotation as Tools to Delineate Functionally Relevant Risk Alleles at IKZF1 and IKZF3 in Systemic Lupus Erythematosus. (PMID:33182226)
• Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them. (PMID:33499314)
• A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation. (PMID:33689703)
• [Relationship between IKZF3 Gene Single Nucleotide Polymorphisms and Childhood Acute Lymphoblastic Leukemia]. (PMID:34105458)
• A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS. (PMID:34155405)
• Aiolos regulates eosinophil migration into tissues. (PMID:34341502)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ikzf3	ENSMUSG00000018168
rattus_norvegicus	Ikzf3	ENSRNOG00000007200
drosophila_melanogaster	CG14442	FBGN0029893
drosophila_melanogaster	CG14440	FBGN0029894

Paralogs (11): IKZF2 (ENSG00000030419), ZNF821 (ENSG00000102984), ZNF639 (ENSG00000121864), IKZF4 (ENSG00000123411), ZNF382 (ENSG00000161298), ZNF613 (ENSG00000176024), IKZF1 (ENSG00000185811), ZNF567 (ENSG00000189042), ZNF649 (ENSG00000198093), ZNF564 (ENSG00000249709), ZNF350 (ENSG00000256683)

Protein

Protein identifiers

Zinc finger protein Aiolos — Q9UKT9 (reviewed: Q9UKT9)

Alternative names: Ikaros family zinc finger protein 3

All UniProt accessions (2): A0A0C4DGN9, Q9UKT9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner.

Subunit / interactions. Homodimer. Heterodimer with other IKAROS family members. Interacts with IKZF4 and IKZF5. Interacts with IKZF1. Interacts with HRAS. Interacts with FOXP3; this interaction may be required for silencing target genes and regulating the suppressive activity of FOXP3-positive regulatory T-cells (Treg). Interacts with BCL21L isoform Bcl-X(L); this interaction blocks the anti-apoptotic role of BCL21L. Associates with histone deacetylase complexes containing HDAC1, MTA2 and SIN3A.

Subcellular location. Nucleus. Cytoplasm Nucleus Nucleus Nucleus Nucleus. Cytoplasm Cytoplasm.

Tissue specificity. Expressed most strongly in peripheral blood leukocytes, the spleen, and the thymus.

Post-translational modifications. Phosphorylation on tyrosine residues induced by IL2 is required for dissociation from HRAS and nuclear translocation of IKZF3 in T-cells. Phosphorylation on tyrosine residues induced by IL4 is required for dissociation from Bcl-X(L) in T-cells.

Disease relevance. Immunodeficiency 84 (IMD84) [MIM:619437] An autosomal recessive immunologic disorder characterized by recurrent sinopulmonary infections from childhood associated with low levels of B cells and impaired early B-cell development. There may also be variable T-cell abnormalities. Patients have increased susceptibility to infection with Epstein-Barr virus and a propensity for the development of lymphoma in adulthood. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. C2H2-type 5 and C2H2-type 6 mediate homodimerization and heterodimerization.

Induction. Up-regulated by TGFB1 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in activated AHR T-cells.

Similarity. Belongs to the Ikaros C2H2-type zinc-finger protein family.

Isoforms (16)

UniProt ID	Names	Canonical?
Q9UKT9-1	1, Aio-1	yes
Q9UKT9-2	2, Aio-del4
Q9UKT9-3	3, Aio-del5
Q9UKT9-4	4, Aio-del6
Q9UKT9-5	5, Aio-del4,5
Q9UKT9-6	6, Aio-del5,6
Q9UKT9-7	7, Aio-del2
Q9UKT9-8	8, Aio-del2,5
Q9UKT9-9	9, Aio-del3
Q9UKT9-10	10, Aio-del3,4
Q9UKT9-11	11, Aio-del3,4,5
Q9UKT9-12	12, Aio-del3,4,5,6
Q9UKT9-13	13, Aio-del4,5,6
Q9UKT9-14	14, Aio-1-5a
Q9UKT9-15	15, Aio-del4-5a
Q9UKT9-16	16

RefSeq proteins (16): NP_001244337, NP_001244338, NP_001244339, NP_001244340, NP_001244341, NP_001244342, NP_001244343, NP_001271443, NP_001271444, NP_001271445, NP_036613, NP_899051, NP_899052, NP_899053, NP_899054, NP_899055 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050589	Ikaros_C2H2-ZF	Family

Pfam: PF00096

UniProt features (43 total): splice variant 14, zinc finger region 6, sequence conflict 6, modified residue 4, cross-link 4, compositionally biased region 3, region of interest 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKT9-F1	48.06	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 22, 42, 326, 378, 61, 73, 100, 245

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 303 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_B_CELL_ACTIVATION, GOBP_B_CELL_PROLIFERATION, MEF2_02, USF_C, FOXD3_01, AACWWCAANK_UNKNOWN, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, PID_IL2_1PATHWAY, GOBP_REGULATION_OF_HEMOPOIESIS, NKX62_Q2, GOBP_LEUKOCYTE_PROLIFERATION

GO Biological Process (11): regulation of transcription by RNA polymerase II (GO:0006357), mesoderm development (GO:0007498), response to bacterium (GO:0009617), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), regulation of B cell proliferation (GO:0030888), regulation of apoptotic process (GO:0042981), regulation of B cell differentiation (GO:0045577), regulation of lymphocyte differentiation (GO:0045619), B cell activation (GO:0042113), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (14): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), sequence-specific DNA binding (GO:0043565), protein heterodimerization activity (GO:0046982), promoter-specific chromatin binding (GO:1990841), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte differentiation	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of B cell activation	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
protein dimerization activity	2
tissue development	1
response to other organism	1
B cell activation	1
T cell activation	1
B cell proliferation	1
regulation of lymphocyte proliferation	1
apoptotic process	1
regulation of programmed cell death	1
B cell differentiation	1
regulation of lymphocyte differentiation	1
regulation of lymphocyte activation	1
regulation of leukocyte differentiation	1
lymphocyte activation	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
transition metal ion binding	1
protein binding	1
identical protein binding	1
enzyme binding	1
DNA binding	1
chromatin binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKZF3	CRBN	Q96SW2	997
IKZF3	ZPBP2	Q6X784	929
IKZF3	PAX5	Q02548	880
IKZF3	EBF1	Q9UH73	879
IKZF3	GSDMB	Q8TAX9	849
IKZF3	ORMDL3	Q8N138	799
IKZF3	RUNX1	Q01196	777
IKZF3	RUNX3	Q13761	769
IKZF3	LEF1	Q9UJU2	755
IKZF3	POU2AF1	Q16633	751
IKZF3	SPIB	Q01892	734
IKZF3	IRF4	Q15306	647
IKZF3	ZPBP	Q9BS86	643
IKZF3	DDB1	Q16531	626
IKZF3	GRB7	Q14451	626

IntAct

723 interactions, top by confidence:

A	B	Type	Score
IKZF3	PRKAB2	psi-mi:“MI:0915”(physical association)	0.910
IKZF3	RAD51D	psi-mi:“MI:0915”(physical association)	0.850
IKZF3	EFHC1	psi-mi:“MI:0915”(physical association)	0.850
TSTD2	IKZF3	psi-mi:“MI:0915”(physical association)	0.850
IKZF3	ATPAF2	psi-mi:“MI:0915”(physical association)	0.850
RAD51D	IKZF3	psi-mi:“MI:0915”(physical association)	0.850
EFHC1	IKZF3	psi-mi:“MI:0915”(physical association)	0.850
IKZF3	TSTD2	psi-mi:“MI:0915”(physical association)	0.850
IKZF3	POLR1C	psi-mi:“MI:0915”(physical association)	0.840
IKZF3	ARMC7	psi-mi:“MI:0915”(physical association)	0.840
ARMC7	IKZF3	psi-mi:“MI:0915”(physical association)	0.840
POLR1C	IKZF3	psi-mi:“MI:0915”(physical association)	0.840
IKZF3	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.830
TBC1D22B	IKZF3	psi-mi:“MI:0915”(physical association)	0.830
IKZF3	GRB2	psi-mi:“MI:0915”(physical association)	0.790
GRB2	IKZF3	psi-mi:“MI:0915”(physical association)	0.790
IKZF3	MORN3	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (430): IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid), IKZF3 (Two-hybrid)

ESM2 similar proteins: A0JPB4, A1L1J6, A2VDW9, A4IFJ6, O00409, O08876, O08900, O13089, O15060, O15062, O42410, O57415, O60315, O75626, O89091, P14404, P25932, P36197, P37275, P55878, P55879, P81183, Q03267, Q0VDT2, Q13422, Q33BP8, Q3BJS3, Q3UH06, Q499D0, Q5R9W9, Q5T0B9, Q5ZLR2, Q5ZM39, Q60636, Q62255, Q62947, Q64318, Q6DBW0, Q6NRM0, Q6XDT4

Diamond homologs: A0JPB4, A2VDW9, A4IFJ6, H2L008, O08900, O13089, O42410, O62537, O62538, O62541, O96785, P05084, P13361, P81183, Q01778, Q01791, Q03267, Q13422, Q25514, Q5R9W9, Q5ZLR2, Q6DBW0, Q6NRM0, Q6XDT4, Q6XDT6, Q8BU00, Q8C208, Q90ZS6, Q925H1, Q9H2S9, Q9H5V7, Q9UHF7, Q9UKS7, Q9UKT9, Q5JPB2, Q65XX7, O18326, O46232, O46234, O46236

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
lenalidomide	“down-regulates quantity by destabilization”	IKZF3	“chemical inhibition”
IKZF3	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
CRBN	“down-regulates quantity by destabilization”	IKZF3	ubiquitination
IKZF3	“up-regulates activity”	B_cell_maturation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — CHOL, CLLSLL, DLBCLNOS.

Clinical variants and AI predictions

ClinVar

79 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	57
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1184728	NM_012481.5(IKZF3):c.475G>C (p.Gly159Arg)	Pathogenic
3775109	NM_012481.5(IKZF3):c.1_7delATGGAAG (p.Met1fs)	Likely pathogenic

SpliceAI

1778 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39777773:T:TC	acceptor_gain	1.0000
17:39777781:A:AC	acceptor_gain	1.0000
17:39777781:A:C	acceptor_gain	1.0000
17:39777783:G:C	acceptor_gain	1.0000
17:39777783:G:GC	acceptor_gain	1.0000
17:39788375:C:CC	acceptor_gain	1.0000
17:39792930:TCAT:T	acceptor_gain	1.0000
17:39792931:CATC:C	acceptor_gain	1.0000
17:39792934:C:CC	acceptor_gain	1.0000
17:39829382:CTCA:C	donor_loss	1.0000
17:39829383:TCA:T	donor_loss	1.0000
17:39829384:CACCT:C	donor_loss	1.0000
17:39829385:ACCT:A	donor_gain	1.0000
17:39829386:C:A	donor_loss	1.0000
17:39829386:CCTC:C	donor_gain	1.0000
17:39829388:T:TA	donor_gain	1.0000
17:39829485:CTTT:C	acceptor_gain	1.0000
17:39829486:TTT:T	acceptor_gain	1.0000
17:39829487:TT:T	acceptor_gain	1.0000
17:39829489:C:CC	acceptor_gain	1.0000
17:39829490:T:C	acceptor_loss	1.0000
17:39832096:ACCT:A	donor_loss	1.0000
17:39832097:C:G	donor_loss	1.0000
17:39832147:TATAT:T	acceptor_gain	1.0000
17:39832149:TAT:T	acceptor_gain	1.0000
17:39832149:TATC:T	acceptor_loss	1.0000
17:39832151:TC:T	acceptor_loss	1.0000
17:39832152:C:CC	acceptor_gain	1.0000
17:39832152:CT:C	acceptor_loss	1.0000
17:39832153:T:A	acceptor_loss	1.0000

AlphaMissense

3428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39788348:A:G	C207R	1.000
17:39788357:A:G	C204R	1.000
17:39791480:A:C	C176W	1.000
17:39791482:A:G	C176R	1.000
17:39791520:C:G	R163P	1.000
17:39791526:A:G	L161P	1.000
17:39791543:A:C	F155L	1.000
17:39791543:A:T	F155L	1.000
17:39791544:A:G	F155S	1.000
17:39791545:A:G	F155L	1.000
17:39791566:A:G	C148R	1.000
17:39791570:G:C	F146L	1.000
17:39791570:G:T	F146L	1.000
17:39791572:A:G	F146L	1.000
17:39792691:G:C	H136D	1.000
17:39765836:A:G	F495S	0.999
17:39765876:A:G	C482R	0.999
17:39765949:G:C	C457W	0.999
17:39765951:A:G	C457R	0.999
17:39765960:A:G	C454R	0.999
17:39788346:A:C	C207W	0.999
17:39788347:C:G	C207S	0.999
17:39788347:C:T	C207Y	0.999
17:39788348:A:T	C207S	0.999
17:39791420:A:C	H196Q	0.999
17:39791420:A:T	H196Q	0.999
17:39791430:A:G	L193P	0.999
17:39791432:A:C	H192Q	0.999
17:39791432:A:T	H192Q	0.999
17:39791434:G:C	H192D	0.999

dbSNP variants (sampled 300 via entrez): RS1000024296 (17:39797369 C>T), RS1000034861 (17:39803637 C>T), RS1000106607 (17:39803797 G>A), RS1000121134 (17:39830224 G>A,C), RS1000123956 (17:39769884 C>A), RS1000195121 (17:39830625 A>G), RS1000237024 (17:39862552 G>A,T), RS1000239686 (17:39783756 C>T), RS1000244163 (17:39844234 G>C), RS1000300241 (17:39799009 G>GTGTA), RS1000324224 (17:39776216 A>C), RS1000348089 (17:39811124 T>C), RS1000401881 (17:39824524 G>A), RS1000422493 (17:39805101 G>A), RS1000430084 (17:39771284 CAAG>C)

Disease associations

OMIM: gene MIM:606221 | disease phenotypes: MIM:619437

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 84	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency 84	Moderate	AD

Mondo (1): immunodeficiency 84 (MONDO:0030333)

Orphanet (1): Combined immunodeficiency-cancer predisposing syndrome due to AIOLOS deficiency (Orphanet:697385)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001744	Splenomegaly
HP:0002718	Recurrent bacterial infections
HP:0009789	Perianal abscess
HP:0010976	Decreased total B cell count
HP:0012191	B-cell lymphoma
HP:0020072	Persistent EBV viremia

GWAS associations

64 associations (top):

Study	Trait	p-value
GCST000408_4	Primary biliary cholangitis	8.000000e-06
GCST000624_15	Ulcerative colitis	3.000000e-08
GCST000733_2	Primary biliary cholangitis	2.000000e-09
GCST000879_10	Crohn’s disease	2.000000e-09
GCST000964_1	Ulcerative colitis	5.000000e-11
GCST001685_2	Primary biliary cholangitis	4.000000e-09
GCST001725_54	Inflammatory bowel disease	4.000000e-38
GCST002069_20	Systemic lupus erythematosus and Systemic sclerosis	7.000000e-06
GCST002083_32	Self-reported allergy	9.000000e-09
GCST002318_118	Rheumatoid arthritis	6.000000e-10
GCST002318_70	Rheumatoid arthritis	2.000000e-12
GCST002322_13	Asthma and hay fever	4.000000e-07
GCST003097_30	Pediatric autoimmune diseases	3.000000e-07
GCST003129_15	Primary biliary cholangitis	3.000000e-11
GCST003155_23	Systemic lupus erythematosus	8.000000e-09
GCST003156_39	Systemic lupus erythematosus	6.000000e-09
GCST003180_7	Atopic march	5.000000e-08
GCST003589_1	Bronchial hyperresponsiveness in asthma	3.000000e-20
GCST003622_54	Systemic lupus erythematosus	4.000000e-06
GCST003814_8	Selective IgA deficiency	7.000000e-07
GCST004131_33	Inflammatory bowel disease	2.000000e-26
GCST004132_116	Crohn’s disease	1.000000e-16
GCST004133_16	Ulcerative colitis	2.000000e-16
GCST004145_7	Primary biliary cholangitis	8.000000e-11
GCST004390_3	Asthma	1.000000e-12
GCST004600_142	Eosinophil percentage of white cells	2.000000e-17
GCST004600_143	Eosinophil percentage of white cells	1.000000e-17
GCST004606_31	Eosinophil count	2.000000e-09
GCST004617_120	Eosinophil percentage of granulocytes	2.000000e-19
GCST004623_83	Neutrophil percentage of granulocytes	7.000000e-18

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0007755	atopic march
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4296167 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630744 (PROTEIN-PROTEIN INTERACTION), CHEMBL4739707 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 118,809 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL43452	POMALIDOMIDE	4	13,354
CHEMBL848	LENALIDOMIDE	4	5,256
CHEMBL468	THALIDOMIDE	4	97,393
CHEMBL3989927	IBERDOMIDE	3	1,300
CHEMBL3989934	AVADOMIDE	2	1,506

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9908694	IKZF3		0.00	0

ChEMBL bioactivities

58 potent at pChembl≥5 of 58 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	EC50	0.1	nM	CHEMBL4645677
10.00	EC50	0.1	nM	CHEMBL4640365
10.00	EC50	0.1	nM	CHEMBL4638224
10.00	EC50	0.1	nM	CHEMBL4636670
10.00	EC50	0.1	nM	CHEMBL4647905
10.00	EC50	0.1	nM	CHEMBL4647587
10.00	EC50	0.1	nM	CHEMBL4637801
10.00	EC50	0.1	nM	CHEMBL4645982
10.00	EC50	0.1	nM	CHEMBL4636184
10.00	EC50	0.1	nM	CHEMBL4644660
10.00	EC50	0.1	nM	CHEMBL4637622
9.70	EC50	0.2	nM	CHEMBL4641034
9.70	EC50	0.2	nM	CHEMBL4642904
9.52	EC50	0.3	nM	CHEMBL4645692
9.52	EC50	0.3	nM	CHEMBL4642197
9.52	EC50	0.3	nM	CHEMBL4646021
9.52	EC50	0.3	nM	CHEMBL4648954
9.40	EC50	0.4	nM	CHEMBL4642361
9.40	EC50	0.4	nM	CHEMBL4639846
9.30	EC50	0.5	nM	IBERDOMIDE
9.30	EC50	0.5	nM	CHEMBL4647512
9.30	EC50	0.5	nM	CHEMBL4634342
9.30	EC50	0.5	nM	CHEMBL4647343
9.22	EC50	0.6	nM	CHEMBL4641342
9.22	EC50	0.6	nM	CHEMBL4645264
9.15	EC50	0.7	nM	CHEMBL4634712
9.00	EC50	1	nM	CHEMBL4642706
9.00	EC50	1	nM	CHEMBL4643542
9.00	EC50	1	nM	IBERDOMIDE
8.82	EC50	1.5	nM	CHEMBL4645905
8.68	EC50	2.1	nM	CHEMBL4644747
8.62	EC50	2.4	nM	CHEMBL4645564
8.52	EC50	3	nM	CHEMBL4642035
8.48	EC50	3.3	nM	CHEMBL4642316
8.30	EC50	5	nM	CHEMBL4170596
8.12	EC50	7.5	nM	CHEMBL4638669
7.92	EC50	12	nM	CHEMBL5618808
7.70	EC50	20	nM	POMALIDOMIDE
7.70	EC50	20	nM	AVADOMIDE
7.66	EC50	22	nM	POMALIDOMIDE
7.30	EC50	50	nM	LENALIDOMIDE
7.16	EC50	70	nM	CHEMBL5430384
7.16	EC50	70	nM	LENALIDOMIDE
7.06	EC50	87	nM	LENALIDOMIDE
6.96	EC50	110	nM	CHEMBL5620230
6.89	EC50	130	nM	CHEMBL5417302
6.85	EC50	142	nM	CHEMBL5412109
6.51	EC50	312	nM	CHEMBL5427029
6.51	EC50	310	nM	CHEMBL5618377
6.48	EC50	330	nM	THALIDOMIDE

PubChem BioAssay actives

54 with measured affinity, of 421 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[4-[[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]oxymethyl]phenyl]methyl]piperazin-1-yl]-3-fluorobenzonitrile	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[[4-(3-fluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[4-(2,4-dichlorophenyl)piperazine-1-carbonyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[4-(2,4-difluorophenyl)piperazine-1-carbonyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[4-(4-chlorophenyl)piperazine-1-carbonyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
(3S)-3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[3-oxo-7-[[4-[(4-propan-2-ylpiperidin-1-yl)methyl]phenyl]methoxy]-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[3-oxo-7-[[4-[(4-phenylpiperazin-1-yl)methyl]phenyl]methoxy]-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0001	uM
3-[7-[[4-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0002	uM
3-[7-[[4-[[4-(2,4-dichlorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0002	uM
3-[7-[[4-[[4-(2,6-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0003	uM
3-[7-[[4-[4-(4-fluorophenyl)piperazine-1-carbonyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0003	uM
3-[7-[[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0003	uM
3-[3-oxo-7-[[4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]methoxy]-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0003	uM
5-[4-[[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]oxymethyl]phenyl]methyl]piperazin-1-yl]pyridine-2-carboxamide	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0004	uM
3-[3-oxo-7-[[4-[(4-pyridin-2-ylpiperazin-1-yl)methyl]phenyl]methoxy]-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0004	uM
(3R)-3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0005	uM
3-[7-[[4-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0005	uM
3-[7-[[4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0005	uM
(3S)-3-[7-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1387872: Induction of cereblon-mediated aiolos degradation in human DF15 cells expressing ePL-tagged aiolos after 4 hrs by luminometric analysis	ec50	0.0005	uM
3-[7-[[4-[[4-(2,4-dichlorophenyl)-2-oxopiperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0006	uM
3-[3-oxo-7-[[4-[[4-(trifluoromethyl)piperidin-1-yl]methyl]phenyl]methoxy]-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0006	uM
3-[7-[[4-[[4-(5-fluoro-2-pyridinyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0007	uM
2-[4-[[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]oxymethyl]phenyl]methyl]piperazin-1-yl]pyridine-3-carbonitrile	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0010	uM
3-[7-[[4-[(4-methylpiperidin-1-yl)methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0010	uM
3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methylamino]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0015	uM
2-(2,6-dioxopiperidin-3-yl)-4-[[4-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]isoindole-1,3-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0021	uM
4-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0024	uM
3-[7-[[4-[(4-methylpiperazin-1-yl)methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0030	uM
4-[[4-[[4-(2,4-dichlorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0033	uM
1-(3-chloro-4-methylphenyl)-3-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]urea	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.0050	uM
3-(3-oxo-7-phenylmethoxy-1H-isoindol-2-yl)piperidine-2,6-dione	1667517: Induction of CRBN-mediated pLOC-ePL-tagged aiolos (unknown origin) degradation in human DF15 cells assessed as minimum protein remaining incubated for 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay	ec50	0.0075	uM
2,2,2-trichloroethyl (1S)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]cycloprop-2-ene-1-carboxylate	2130917: Induction of N-terminal HiBiT tag knocked in IKZF3 degradation in human DF15 cells incubated for 60 mins by Nano-Glo HiBiT lytic reagent based assay	ec50	0.0120	uM
Pomalidomide	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.0200	uM
3-(5-amino-2-methyl-4-oxoquinazolin-3-yl)piperidine-2,6-dione	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.0200	uM
3-[6-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]benzimidazol-1-yl]piperidine-2,6-dione	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.0700	uM
Lenalidomide	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.0700	uM
2,2,2-trichloroethyl (1R)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]cycloprop-2-ene-1-carboxylate	2130917: Induction of N-terminal HiBiT tag knocked in IKZF3 degradation in human DF15 cells incubated for 60 mins by Nano-Glo HiBiT lytic reagent based assay	ec50	0.1100	uM
3-(benzimidazol-1-yl)piperidine-2,6-dione	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.1300	uM
3-(6-aminobenzimidazol-1-yl)piperidine-2,6-dione	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.1420	uM
2,2,2-trichloroethyl (1R)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]cycloprop-2-ene-1-carboxylate	2130917: Induction of N-terminal HiBiT tag knocked in IKZF3 degradation in human DF15 cells incubated for 60 mins by Nano-Glo HiBiT lytic reagent based assay	ec50	0.3100	uM
3-(5-aminobenzimidazol-1-yl)piperidine-2,6-dione	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.3120	uM
Thalidomide	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.3300	uM
4-amino-N-(2,6-dioxopiperidin-3-yl)benzamide	2023108: Induction of ePL tagged Aiolos degradation in human DF15 cells incubated for 4 hrs by luminescence based assay	ec50	0.6070	uM
2,2,2-trichloroethyl (1S)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]cycloprop-2-ene-1-carboxylate	2130917: Induction of N-terminal HiBiT tag knocked in IKZF3 degradation in human DF15 cells incubated for 60 mins by Nano-Glo HiBiT lytic reagent based assay	ec50	0.9000	uM
2,2,2-trichloroethyl (1S)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]cycloprop-2-ene-1-carboxylate	2130917: Induction of N-terminal HiBiT tag knocked in IKZF3 degradation in human DF15 cells incubated for 60 mins by Nano-Glo HiBiT lytic reagent based assay	ec50	1.3000	uM
2,2,2-trichloroethyl (1R)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]cycloprop-2-ene-1-carboxylate	2130917: Induction of N-terminal HiBiT tag knocked in IKZF3 degradation in human DF15 cells incubated for 60 mins by Nano-Glo HiBiT lytic reagent based assay	ec50	3.7000	uM

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
GSK-J4	decreases expression	1
afuresertib	affects cotreatment, decreases expression, increases reaction	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	affects expression, increases expression, increases reaction	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
pomalidomide	decreases expression, increases reaction, affects cotreatment	1
abrine	increases expression	1
2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl ester	affects cotreatment, increases expression	1
Decitabine	affects methylation, increases expression, increases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases expression	1
Dexamethasone	affects cotreatment, decreases expression, increases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Diuron	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Nickel	increases expression	1
T-2 Toxin	increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

101 unique, capped per target: 100 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4219435	Binding	Induction of cereblon-mediated aiolos degradation in human DF15 cells expressing ePL-tagged aiolos after 4 hrs by luminometric analysis	A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. — J Med Chem
CHEMBL5346089	Functional	In vivo protac activity at CRBN/IKZF3 in CB17-SCID mouse xenografted with human TMD8 cells assessed as degradation of IKZF3 protein in tumor at 10 to 90 mg/kg,po administration for 25 days by flow cytomtery	Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton’s Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies. — J Med Chem

Cellosaurus cell lines

19 cell lines: 19 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0179	BT-474	Cancer cell line	Female
CVCL_4V65	BT474-5FU[r]	Cancer cell line	Female
CVCL_4Y08	BT-474/CMV-Luc	Cancer cell line	Female
CVCL_A2GH	LR-BT474	Cancer cell line	Female
CVCL_A4AK	BT-474 Tam2	Cancer cell line	Female
CVCL_A4CL	BT-474 Ecadherin EmGFP	Cancer cell line	Female
CVCL_AQ07	BT-474 Clone 5	Cancer cell line	Female
CVCL_AR86	BT-474 Tam1	Cancer cell line	Female
CVCL_AR96	BT-474 EEI	Cancer cell line	Female
CVCL_C9CU	BT-474-Luc2	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.