IKZF1

Summary

IKZF1 (IKAROS family zinc finger 1, HGNC:13176) is a protein-coding gene on chromosome 7p12.2, encoding DNA-binding protein Ikaros (Q13422). Transcription regulator of hematopoietic cell differentiation. In precision oncology, IKZF1 Deletion confers sensitivity to Methotrexate + Daunorubicin + Cytarabine + Fludarabine + Imatinib in B-lymphoblastic Leukemia/lymphoma (CIViC Level B). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a transcription factor that belongs to the family of zinc-finger DNA-binding proteins associated with chromatin remodeling. The expression of this protein is restricted to the fetal and adult hemo-lymphopoietic system, and it functions as a regulator of lymphocyte differentiation. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. Most isoforms share a common C-terminal domain, which contains two zinc finger motifs that are required for hetero- or homo-dimerization, and for interactions with other proteins. The isoforms, however, differ in the number of N-terminal zinc finger motifs that bind DNA and in nuclear localization signal presence, resulting in members with and without DNA-binding properties. Only a few isoforms contain the requisite three or more N-terminal zinc motifs that confer high affinity binding to a specific core DNA sequence element in the promoters of target genes. The non-DNA-binding isoforms are largely found in the cytoplasm, and are thought to function as dominant-negative factors. Overexpression of some dominant-negative isoforms have been associated with B-cell malignancies, such as acute lymphoblastic leukemia (ALL).

Source: NCBI Gene 10320 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pancytopenia due to IKZF1 mutations (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 140
• Clinical variants (ClinVar): 462 total — 6 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 54 downstream targets (CollecTRI)
• MANE Select transcript: NM_006060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13176
Approved symbol	IKZF1
Name	IKAROS family zinc finger 1
Location	7p12.2
Locus type	gene with protein product
Status	Approved
Aliases	hIk-1, LyF-1, Hs.54452, IKAROS, PPP1R92
Ensembl gene	ENSG00000185811
Ensembl biotype	protein_coding
OMIM	603023
Entrez	10320

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 44 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000331340, ENST00000346667, ENST00000359197, ENST00000413698, ENST00000426121, ENST00000438033, ENST00000439701, ENST00000462201, ENST00000471793, ENST00000484847, ENST00000492119, ENST00000492782, ENST00000615491, ENST00000641948, ENST00000642219, ENST00000645066, ENST00000646110, ENST00000698573, ENST00000698574, ENST00000698575, ENST00000698576, ENST00000698577, ENST00000858039, ENST00000858040, ENST00000858041, ENST00000858042, ENST00000858043, ENST00000858044, ENST00000858045, ENST00000858046, ENST00000858047, ENST00000858048, ENST00000858049, ENST00000858050, ENST00000858051, ENST00000858052, ENST00000858053, ENST00000858054, ENST00000858055, ENST00000858056, ENST00000858057, ENST00000858058, ENST00000858059, ENST00000858060, ENST00000858061, ENST00000858062, ENST00000858063, ENST00000858064, ENST00000858065, ENST00000971279, ENST00000971280

RefSeq mRNA: 18 — MANE Select: NM_006060 NM_001220765, NM_001220767, NM_001220768, NM_001220770, NM_001220771, NM_001291837, NM_001291838, NM_001291839, NM_001291840, NM_001291841, NM_001291842, NM_001291843, NM_001291844, NM_001291845, NM_001291846, NM_001291847, NM_001410879, NM_006060

CCDS: CCDS59055, CCDS69299, CCDS75596, CCDS78232, CCDS78233, CCDS87502, CCDS94102

Canonical transcript exons

ENST00000331340 — 8 exons

Exon	Start	End
ENSE00003490611	50319048	50319101
ENSE00003496551	50382540	50382707
ENSE00003520749	50376533	50376793
ENSE00003597423	50327638	50327757
ENSE00003830192	50304716	50304922
ENSE00003974049	50399918	50405101
ENSE00003974053	50387345	50387470
ENSE00003974057	50391729	50391863

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 96.71.

FANTOM5 (CAGE): breadth broad, TPM avg 26.6618 / max 2171.7223, expressed in 665 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78630	10.6635	555
78624	6.6432	534
78629	3.6170	455
78627	1.5064	192
78634	1.4780	219
78633	0.7544	119
78628	0.5355	163
78626	0.3851	136
78635	0.2012	58
78625	0.1984	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
leukocyte	CL:0000738	96.71	gold quality
monocyte	CL:0000576	96.66	gold quality
mononuclear cell	CL:0000842	96.61	gold quality
bone marrow	UBERON:0002371	96.44	gold quality
trabecular bone tissue	UBERON:0002483	96.37	gold quality
blood	UBERON:0000178	96.27	gold quality
granulocyte	CL:0000094	96.19	gold quality
bone marrow cell	CL:0002092	96.00	gold quality
lymph node	UBERON:0000029	94.87	gold quality
epithelium of nasopharynx	UBERON:0001951	93.25	gold quality
thymus	UBERON:0002370	92.93	gold quality
vermiform appendix	UBERON:0001154	92.07	gold quality
spleen	UBERON:0002106	90.93	gold quality
colonic epithelium	UBERON:0000397	89.77	gold quality
superficial temporal artery	UBERON:0001614	89.37	gold quality
buccal mucosa cell	CL:0002336	89.04	silver quality
tonsil	UBERON:0002372	88.74	gold quality
caecum	UBERON:0001153	88.42	gold quality
endothelial cell	CL:0000115	87.50	gold quality
amniotic fluid	UBERON:0000173	86.18	gold quality
parietal pleura	UBERON:0002400	85.53	gold quality
pleura	UBERON:0000977	84.93	gold quality
visceral pleura	UBERON:0002401	84.76	gold quality
ileal mucosa	UBERON:0000331	82.76	gold quality
palpebral conjunctiva	UBERON:0001812	82.59	gold quality
germinal epithelium of ovary	UBERON:0001304	81.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.54	gold quality
small intestine	UBERON:0002108	79.65	gold quality
upper lobe of left lung	UBERON:0008952	78.88	gold quality
oral cavity	UBERON:0000167	78.71	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1002.85
E-MTAB-11268	yes	380.19
E-MTAB-8142	yes	52.39
E-CURD-88	yes	40.97
E-HCAD-1	yes	36.46
E-GEOD-135922	yes	26.36
E-CURD-122	yes	20.98
E-MTAB-9543	yes	16.14
E-MTAB-8410	yes	13.28
E-ANND-3	yes	12.88
E-CURD-119	yes	7.60
E-CURD-112	yes	4.90
E-CURD-89	no	684.90
E-GEOD-100618	no	630.17
E-MTAB-9221	no	490.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

54 targets.

Target	Regulation
BCL2L1
CD3D
CD4	Repression
DNTT	Unknown
DTX1	Unknown
FAAH
FGFR4	Activation
FLT3	Activation
GABRG2
GATA2	Repression
GATA3	Unknown
GH1
GHRH	Activation
GZMB	Unknown
HBG1	Unknown
HES1	Unknown
IFNG	Activation
IFNLR1
IGLL1	Unknown
IKZF3	Activation
IL10	Activation
IL13	Repression
IL2	Activation
IL21	Activation
IL22	Activation
IL4	Activation
IL7R	Unknown
INPP5D
KIT	Unknown
LDLR	Unknown

JASPAR motifs

Motif	Name	Family
MA1508.1	IKZF1	Factors with multiple dispersed zinc fingers
MA1508.2	IKZF1	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:27664237

Upstream regulators (CollecTRI, top): IRF4, IRF5, IRF8

miRNA regulators (miRDB)

142 targeting IKZF1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A novel Ikaros isoform “Ikx” is the predominant Ikaros protein present in normal cord blood and bone marrow cells, but not in leukemia cell lines. (PMID:11489963)
• role in unconventional potentiation of gene expression (PMID:11799125)
• Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros (PMID:11812772)
• REVIEW:Role of ikaros gene expression and post-transcriptional mechanisms in leukemic processes. (PMID:11908734)
• The expression of Ikaros in a panel of T-cell luekemia/lymphoma cell lines showed that irrespective of their developmental stages, the predominant isoforms epressed were Ik-1,2, and 3. (PMID:11937265)
• In contrast to children, adult acute myeloid leukemia cells do not express nonfunctional Ikaros isoforms. (PMID:12412579)
• Ikaros proteins function in myeloid as well as lymphoid differentiation, and specific Ikaros isoforms may play a role in regulating lineage commitment decisions. (PMID:12626565)
• Ikaros has a role in progesterone activation of fatty acid amide hydrolase in human T lymphocytes (PMID:12799380)
• Constitutional deletion of the ZNFN1A1 gene in a Greig cephalopolysyndactyly patient may have resulted in an increased risk of acute lymphoblastic leukemia. (PMID:15390181)
• Wild-type Ikaros (Ik1) inhibits growth hormone mRNA and protein expression but stimulates prolactin mRNA and protein levels. (PMID:15618287)
• Ik is involved in the regulation of STAT4 in human T cells. (PMID:16081070)
• BCR-ABL1 induces aberrant splicing of IKAROS, which interferes with lineage identity and differentiation of pre-B lymphoblastic leukemia cells. (PMID:16205638)
• Ikaros is involved in migration and invasion of extravillous trophoblasts in early placentation. (PMID:16364975)
• Over-expression of a dominant interfering Ikaros isoform exclusively in B cells has profound effects on mature B cell function. (PMID:17357110)
• Retardation gels showed binding activity for Ikaros, NFkappaB and AP4 transcription factors and mutations in their binding sites abolish Aiolos promoter activity. (PMID:17383641)
• AChE-S mRNA induced selective bone marrow upregulation of Ikaros while suppressing FOG, another transcriptional partner of CtBP. (PMID:17476278)
• the NuRD complex makes major contributions to the functions of both Ikaros and Helios and the activities of these proteins may be regulated in part by changes in phosphorylation (PMID:17681952)
• showed Aiolos overexpression in primary lymphoma tissue (PMID:18332232)
• findings suggest that genetic lesions resulting in the loss of Ikaros function are an important event in the development of BCR-ABL1 acute lymphoblastic leukaemia (PMID:18408710)
• a putative role of Ikaros isoform 6 in the development of B-lineage acute lymphoblastic leukemia, by activating the JAK2-STAT5 pathway and thus stimulating the production of Bcl-xl. (PMID:18464116)
• Ikaros regulates the cholesterol uptake metabolic pathway (PMID:18483254)
• Genomic sequence and computational analyses of exon splice junction regions of IKZF1 in Ph+ ALL patients predicted several mutations that may alter alternative splicing. (PMID:18650450)
• both aberrant splicing and genomic deletion leading to different non-DNA-binding Ikaros cDNA transcripts are common features of Philadelphia chromosome-positive acute lymphoblastic leukemia. (PMID:18838475)
• Since the absence of Ikaros also affects GATA-1 recruitment to GATA-2 promoter, we propose that the combinatorial effect of Ikaros and GATA-1 is not restricted to globin gene regulation. (PMID:19114560)
• Ikaros is active in erythropoiesis, especially fetal-to-adult globin switching. Dominant negative isoforms in precursor cells modify erythroid differentiation. Ikaros may control myeloid/erythroid commitment. Review. (PMID:19116116)
• Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell-progenitor ALL. (PMID:19129520)
• Variable Ikaros isoform expression is associated with precursor-B acute lymphoblastic leukemia. (PMID:19131787)
• Ikaros is controlled by the CK2 and PP1 pathways and that a balance between these two signal transduction pathways is essential for normal cellular function and for the prevention of malignant transformation. (PMID:19282287)
• study concludes that Ikaros proteins are active throughout human B-cell differentiation, before and after CD19 appearance (PMID:19285729)
• Identification and molecular characterization of recurrent genomic deletions on 7p12 in the IKZF1 gene in a large cohort of BCR-ABL1-positive acute lymphoblastic leukemia patients (PMID:19589926)
• Inactivation of the Helios gene by homologous recombination does not impair the differentiation and effector function of T cells, which can be compensated for by other members of the Ikaros family. (PMID:19620299)
• identify IKAROS-mediated cell cycle exit as the endpoint of an emerging pathway of pre-B cell receptor-mediated tumor suppression (PMID:19620627)
• deletions are likely to be a genomic alteration that significantly affects the prognosis of Philadelphia chromosome positive adult acute lymphoblastic leukemia (PMID:19770381)
• Inactivation of Ikaros by deletion or mutation is rare in human T-ALL. (PMID:19796813)
• Activation of CRLF2 expression, mutation of of JAK1 or JAK2, and alterations of IKZF1 cooperate to promote B-cell leukemogenesis. (PMID:20139093)
• Inactivation of IKZF1 is associated with childhood acute lymphoblastic leukemia. (PMID:20233627)
• In all of the leukemia and lymphoma cell lines examined Ikaros was present in dominant Ik1 to Ik4 isoforms and small Ik6 isoform was absent (PMID:20432734)
• IKZF1 deletions are associated with relapse in pediatric precursor acute lymphoblastic leukemia. (PMID:20445578)
• Deletions of the transcription factor Ikaros is associated with myeloproliferative neoplasms. (PMID:20508609)
• Significant associations were found for the single nucleotide polymorphism rs4917014 of IKZF1 with renal nephritis and malar rash in patients with systemic lupus erythematosus (PMID:20516000)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ikzf1	ENSDARG00000013539
mus_musculus	Ikzf1	ENSMUSG00000018654
rattus_norvegicus	Ikzf1	ENSRNOG00000004444
drosophila_melanogaster	CG14442	FBGN0029893
drosophila_melanogaster	CG14440	FBGN0029894

Paralogs (11): IKZF2 (ENSG00000030419), ZNF821 (ENSG00000102984), ZNF639 (ENSG00000121864), IKZF4 (ENSG00000123411), ZNF382 (ENSG00000161298), IKZF3 (ENSG00000161405), ZNF613 (ENSG00000176024), ZNF567 (ENSG00000189042), ZNF649 (ENSG00000198093), ZNF564 (ENSG00000249709), ZNF350 (ENSG00000256683)

Protein

Protein identifiers

DNA-binding protein Ikaros — Q13422 (reviewed: Q13422)

Alternative names: Ikaros family zinc finger protein 1, Lymphoid transcription factor LyF-1

All UniProt accessions (10): A0A087WU46, A0A0A0MRA0, A0A2R8Y4D3, A0A2R8Y4T7, A0A2R8YFR0, A0A8V8TMF3, A0A8V8TNQ0, C9JTB0, Q13422, Q3T907

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator of hematopoietic cell differentiation. Binds gamma-satellite DNA. Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs). Function is isoform-specific and is modulated by dominant-negative inactive isoforms.

Subunit / interactions. Heterodimer formed by the various isoforms; this modulates transcription regulator activity. Heterodimer with other IKAROS family members. Interacts with IKZF4 AND IKZF5. Component of the chromatin-remodeling NuRD repressor complex which includes at least HDAC1, HDAC2, RBBP4, RBBP7, IKZF1, MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4. Interacts directly with the CHD4 component of the NuRD complex. Interacts directly with SMARCA4; the interaction associates IKFZ1 with the BAF complex. Interacts with SUMO1; the interaction sumoylates IKAROS, promoted by PIAS2 and PIAS3. Interacts with PIAS2 (isoform alpha); the interaction promotes sumoylation and reduces transcription repression. Interacts, to a lesser extent, with PIAS3. Interacts with PPP1CC; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with IKZF3.

Subcellular location. Nucleus Nucleus Cytoplasm.

Tissue specificity. Abundantly expressed in thymus, spleen and peripheral blood Leukocytes and lymph nodes. Lower expression in bone marrow and small intestine.

Post-translational modifications. Phosphorylation controls cell-cycle progression from late G(1) stage to S stage. Hyperphosphorylated during G2/M phase. Dephosphorylated state during late G(1) phase. Phosphorylation on Thr-140 is required for DNA and pericentromeric location during mitosis. CK2 is the main kinase, in vitro. GSK3 and CDK may also contribute to phosphorylation of the C-terminal serine and threonine residues. Phosphorylation on these C-terminal residues reduces the DNA-binding ability. Phosphorylation/dephosphorylation events on Ser-13 and Ser-295 regulate TDT expression during thymocyte differentiation. Dephosphorylation by protein phosphatase 1 regulates stability and pericentromeric heterochromatin location. Phosphorylated in both lymphoid and non-lymphoid tissues. Phosphorylation at Ser-361 and Ser-364 downstream of SYK induces nuclear translocation. Sumoylated. Simultaneous sumoylation on the 2 sites results in a loss of both HDAC-dependent and HDAC-independent repression. Has no effect on pericentromeric heterochromatin location. Desumoylated by SENP1. Polyubiquitinated.

Disease relevance. Defects in IKZF1 are frequent occurrences (28.6%) in acute lymphoblasic leukemia (ALL). Such alterations or deletions lead to poor prognosis for ALL. Chromosomal aberrations involving IKZF1 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;7)(q27;p12), with BCL6. Immunodeficiency, common variable, 13 (CVID13) [MIM:616873] A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. CVID13 is an autosomal dominant disease associated with a striking decrease in B-cell numbers. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal zinc-fingers 2 and 3 are required for DNA binding as well as for targeting IKFZ1 to pericentromeric heterochromatin. The C-terminal zinc-finger domain is required for dimerization.

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

Isoforms (8)

UniProt ID	Names	Canonical?
Q13422-1	Ik1	yes
Q13422-2	Ik2
Q13422-3	Ik3
Q13422-4	Ik4
Q13422-5	Ik5
Q13422-6	Ik6
Q13422-7	Ik7
Q13422-8	Ikx

RefSeq proteins (18): NP_001207694, NP_001207696, NP_001207697, NP_001207699, NP_001207700, NP_001278766, NP_001278767, NP_001278768, NP_001278769, NP_001278770, NP_001278771, NP_001278772, NP_001278773, NP_001278774, NP_001278775, NP_001278776, NP_001397808, NP_006051* (*=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 (68 total): modified residue 23, splice variant 8, sequence conflict 8, zinc finger region 6, region of interest 5, sequence variant 5, site 3, cross-link 2, mutagenesis site 2, helix 2, chain 1, compositionally biased region 1, turn 1, strand 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8RQC	X-RAY DIFFRACTION	2.15
8TNQ	ELECTRON MICROSCOPY	2.41
8TNR	ELECTRON MICROSCOPY	2.5
9OUK	ELECTRON MICROSCOPY	2.69
9Q2D	ELECTRON MICROSCOPY	2.94
8D7Z	ELECTRON MICROSCOPY	3.1
6H0F	X-RAY DIFFRACTION	3.25
9Y7D	ELECTRON MICROSCOPY	3.26
8TNP	ELECTRON MICROSCOPY	3.3
8D80	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13422-F1	48.22	0.00

Functional residue map

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

Catalytic / active sites (3): 159 (required for both pericentromeric heterochromatin localization and complete dna binding); 162 (required for both pericentromeric heterochromatin localization and complete dna binding); 188 (required for both pericentromeric heterochromatin localization and dna binding)

Post-translational modifications (25): 13, 23, 63, 101, 140, 168, 196, 258, 261, 289, 295, 298, 361, 364, 368, 389, 391, 393, 397, 398 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
159	abolishes binding to dna and has diffuse nuclear localization.
191	abolishes binding to dna and has diffuse nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription

MSigDB gene sets: 426 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_MYELOID_CELL_HOMEOSTASIS, MODULE_45, GOBP_ERYTHROCYTE_HOMEOSTASIS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MAYBURD_RESPONSE_TO_L663536_UP, HAHTOLA_MYCOSIS_FUNGOIDES_DN, MARTINEZ_RB1_TARGETS_UP, FOSTER_TOLERANT_MACROPHAGE_UP, GARY_CD5_TARGETS_DN, BYSTROEM_CORRELATED_WITH_IL5_DN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_MESODERM_DEVELOPMENT

GO Biological Process (7): chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), mesoderm development (GO:0007498), lymphocyte differentiation (GO:0030098), erythrocyte differentiation (GO:0030218), negative regulation of DNA-templated transcription (GO:0045892), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), cytosol (GO:0005829), protein-containing complex (GO:0032991), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
NuRD complex assembly	1
Signaling by NOTCH3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
cellular anatomical structure	3
DNA-templated transcription	2
protein binding	2
cellular component organization	1
transcription by RNA polymerase II	1
tissue development	1
lymphocyte activation	1
mononuclear cell differentiation	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
negative regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome, centromeric region	1
heterochromatin	1
cytoplasm	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKZF1	CRBN	Q96SW2	997
IKZF1	PAX5	Q02548	949
IKZF1	HDAC1	Q13547	947
IKZF1	EBF1	Q9UH73	929
IKZF1	SIN3A	Q96ST3	921
IKZF1	RUNX1	Q01196	911
IKZF1	GATA1	P15976	906
IKZF1	CHD4	Q14839	881
IKZF1	ABL1	P00519	841
IKZF1	RUNX3	Q13761	832
IKZF1	ETV6	P41212	828
IKZF1	SPI1	P17947	811
IKZF1	HDAC2	Q92769	806
IKZF1	SIN3B	O75182	780
IKZF1	IGLL5	B9A064	774

IntAct

234 interactions, top by confidence:

A	B	Type	Score
IKZF1	CTBP2	psi-mi:“MI:0915”(physical association)	0.800
ATOSB	IKZF1	psi-mi:“MI:0915”(physical association)	0.800
CTBP2	IKZF1	psi-mi:“MI:0915”(physical association)	0.800
IKZF1	ATOSB	psi-mi:“MI:0915”(physical association)	0.800
RAD51D	IKZF1	psi-mi:“MI:0915”(physical association)	0.740
ALKBH3	IKZF1	psi-mi:“MI:0915”(physical association)	0.740
IKZF1	ALKBH3	psi-mi:“MI:0915”(physical association)	0.740
IKZF1	RAD51D	psi-mi:“MI:0915”(physical association)	0.740
DCX	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
RWDD2B	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
IKZF1	MTA1	psi-mi:“MI:0915”(physical association)	0.670
IKZF1	WTAP	psi-mi:“MI:0915”(physical association)	0.670
C1orf174	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
GMCL2	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
MCRS1	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
FAM50B	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
IKZF1	C1orf174	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (476): IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (Two-hybrid), IKZF1 (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

22 interactions.

A	Effect	B	Mechanism
CSNK2A1	down-regulates	IKZF1	phosphorylation
CSNK2B	down-regulates	IKZF1	phosphorylation
PPP1CA	up-regulates	IKZF1	dephosphorylation
PPP1CB	up-regulates	IKZF1	dephosphorylation
PPP1CC	up-regulates	IKZF1	dephosphorylation
SYK	up-regulates	IKZF1	phosphorylation
lenalidomide	“down-regulates quantity by destabilization”	IKZF1	“chemical inhibition”
IKZF1	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
IKZF1	“up-regulates activity”	Lymphopoiesis
PP1	up-regulates	IKZF1	dephosphorylation
Cullin4-RBX1-DDB1	“down-regulates quantity by destabilization”	IKZF1	polyubiquitination
BTK	“up-regulates activity”	IKZF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	20.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	7	8.7×	5e-03
chromatin organization	6	8.4×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — AML, ANSC, SKCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	20
Uncertain significance	258
Likely benign	117
Benign	24

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1342126	NM_006060.6(IKZF1):c.247C>T (p.Arg83Ter)	Pathogenic
224777	NM_006060.6(IKZF1):c.629A>G (p.Tyr210Cys)	Pathogenic
224779	NM_006060.6(IKZF1):c.485G>A (p.Arg162Gln)	Pathogenic
224782	NM_006060.5(IKZF1):c.161-8388_589+2308del	Pathogenic
692112	NM_006060.6(IKZF1):c.546C>A (p.Cys182Ter)	Pathogenic
827709	NM_006060.6(IKZF1):c.476A>G (p.Asn159Ser)	Pathogenic
1013000	NM_006060.6(IKZF1):c.356G>C (p.Cys119Ser)	Likely pathogenic
1285540	NM_006060.6(IKZF1):c.530T>C (p.Leu177Pro)	Likely pathogenic
2444367	NM_006060.6(IKZF1):c.1275dup (p.Leu426fs)	Likely pathogenic
2580254	NM_006060.6(IKZF1):c.475A>T (p.Asn159Tyr)	Likely pathogenic
2580255	NM_006060.6(IKZF1):c.271A>T (p.Lys91Ter)	Likely pathogenic
2580256	NM_006060.6(IKZF1):c.436_438delinsGGGCTCCCTAA (p.Gln146fs)	Likely pathogenic
2580258	NM_006060.6(IKZF1):c.450C>A (p.Cys150Ter)	Likely pathogenic
2580259	NM_006060.6(IKZF1):c.336_337insGA (p.Pro113fs)	Likely pathogenic
2907372	NM_006060.6(IKZF1):c.427C>T (p.Arg143Trp)	Likely pathogenic
3352339	NM_006060.6(IKZF1):c.424G>T (p.Glu142Ter)	Likely pathogenic
3572513	NM_006060.6(IKZF1):c.1365_1368del (p.Ser455fs)	Likely pathogenic
3659349	NM_006060.6(IKZF1):c.589+1G>C	Likely pathogenic
3779761	NM_006060.6(IKZF1):c.10_40+46del	Likely pathogenic
4279067	NM_006060.6(IKZF1):c.266G>A (p.Gly89Glu)	Likely pathogenic
4527005	NM_006060.6(IKZF1):c.622C>T (p.Arg208Ter)	Likely pathogenic
4823326	NM_006060.6(IKZF1):c.482_487del (p.Leu161_Arg162del)	Likely pathogenic
547015	NM_006060.6(IKZF1):c.1480_1481del (p.Met494fs)	Likely pathogenic
636776	NM_006060.6(IKZF1):c.589+1G>T	Likely pathogenic
827708	NM_006060.6(IKZF1):c.1401C>G (p.Cys467Trp)	Likely pathogenic
827713	NM_006060.6(IKZF1):c.565A>G (p.Thr189Ala)	Likely pathogenic

SpliceAI

1705 predictions. Top by Δscore:

Variant	Effect	Δscore
7:50304923:G:GG	donor_gain	1.0000
7:50319042:TCTCA:T	acceptor_loss	1.0000
7:50319043:CTCAG:C	acceptor_loss	1.0000
7:50319044:TCA:T	acceptor_loss	1.0000
7:50319045:CA:C	acceptor_loss	1.0000
7:50319046:A:AG	acceptor_gain	1.0000
7:50319046:AGA:A	acceptor_loss	1.0000
7:50319047:G:C	acceptor_loss	1.0000
7:50319047:G:GG	acceptor_gain	1.0000
7:50319047:GAT:G	acceptor_gain	1.0000
7:50327634:TCAG:T	acceptor_loss	1.0000
7:50382704:TCCGG:T	donor_loss	1.0000
7:50382706:CGGTA:C	donor_loss	1.0000
7:50382707:GGTAG:G	donor_loss	1.0000
7:50382708:G:GA	donor_loss	1.0000
7:50382708:G:GG	donor_gain	1.0000
7:50382709:T:A	donor_loss	1.0000
7:50387343:A:AG	acceptor_gain	1.0000
7:50387343:AGTT:A	acceptor_gain	1.0000
7:50387344:G:GG	acceptor_gain	1.0000
7:50387344:GTTG:G	acceptor_gain	1.0000
7:50391728:GTC:G	acceptor_gain	1.0000
7:50304918:TCCAC:T	donor_gain	0.9900
7:50304919:CCAC:C	donor_gain	0.9900
7:50304919:CCACG:C	donor_loss	0.9900
7:50304920:CAC:C	donor_gain	0.9900
7:50304921:AC:A	donor_gain	0.9900
7:50304921:ACG:A	donor_loss	0.9900
7:50304922:CGTG:C	donor_loss	0.9900
7:50304924:TGAGT:T	donor_loss	0.9900

AlphaMissense

3461 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:50376727:T:A	C119S	1.000
7:50376727:T:C	C119R	1.000
7:50376728:G:C	C119S	1.000
7:50376736:T:C	C122R	1.000
7:50376737:G:A	C122Y	1.000
7:50376738:T:G	C122W	1.000
7:50382557:T:C	C147R	1.000
7:50382566:T:C	C150R	1.000
7:50382578:T:C	F154L	1.000
7:50382579:T:C	F154S	1.000
7:50382580:C:A	F154L	1.000
7:50382580:C:G	F154L	1.000
7:50382597:T:C	L160P	1.000
7:50382603:G:C	R162P	1.000
7:50382605:C:G	H163D	1.000
7:50382607:C:A	H163Q	1.000
7:50382607:C:G	H163Q	1.000
7:50382641:T:C	C175R	1.000
7:50382643:C:G	C175W	1.000
7:50382650:T:C	C178R	1.000
7:50382652:C:G	C178W	1.000
7:50382662:T:C	C182R	1.000
7:50382693:T:C	L192P	1.000
7:50387362:T:C	C203R	1.000
7:50387371:T:A	C206S	1.000
7:50387371:T:C	C206R	1.000
7:50387372:G:A	C206Y	1.000
7:50387372:G:C	C206S	1.000
7:50387373:T:G	C206W	1.000
7:50376729:T:G	C119W	0.999

dbSNP variants (sampled 300 via entrez): RS1000068985 (7:50338685 G>A), RS1000114122 (7:50327064 C>A), RS1000134172 (7:50347311 G>T), RS1000135511 (7:50397794 C>T), RS1000175601 (7:50345241 A>C), RS1000179738 (7:50305335 A>G), RS1000201574 (7:50392219 C>G), RS1000231927 (7:50373216 T>C), RS1000391640 (7:50310778 G>A), RS1000399114 (7:50338446 A>G), RS1000425956 (7:50356700 G>A), RS1000454089 (7:50316724 G>A), RS1000482693 (7:50387925 G>A), RS1000486832 (7:50307520 A>G), RS1000496354 (7:50405007 G>A)

Disease associations

OMIM: gene MIM:603023 | disease phenotypes: MIM:616873, MIM:608232, MIM:613067, MIM:300755, MIM:617911

GenCC curated gene-disease

Disease	Classification	Inheritance
pancytopenia due to IKZF1 mutations	Definitive	Autosomal dominant
autoimmune disease	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
autoimmune disease	Moderate	AD
pancytopenia due to IKZF1 mutations	Definitive	AD

Mondo (8): pancytopenia due to IKZF1 mutations (MONDO:0014810), acute lymphoblastic leukemia (MONDO:0004967), chronic myeloid leukemia (MONDO:0011996), teratoma (MONDO:0002601), leukemia, acute lymphocytic, susceptibility to, 2 (MONDO:0013109), immunodeficiency disease (MONDO:0021094), Diamond-Blackfan anemia-like (MONDO:0060662), autoimmune disease (MONDO:0007179)

Orphanet (3): Common variable immunodeficiency phenotype due to IKAROS functional haploinsufficiency (Orphanet:317473), Acute lymphoblastic leukemia (Orphanet:513), Chronic myeloid leukemia (Orphanet:521)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000505	Visual impairment
HP:0000509	Conjunctivitis
HP:0000613	Photophobia
HP:0000621	Entropion
HP:0000795	Abnormality of the urethra
HP:0001561	Polyhydramnios
HP:0001637	Abnormal myocardium morphology
HP:0001645	Sudden cardiac death
HP:0001658	Myocardial infarction
HP:0001733	Pancreatitis
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001874	Abnormality of neutrophils
HP:0001876	Pancytopenia
HP:0001903	Anemia
HP:0001945	Fever
HP:0001960	Hypokalemic metabolic alkalosis
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002017	Nausea and vomiting
HP:0002027	Abdominal pain
HP:0002043	Esophageal stricture
HP:0002091	Restrictive ventilatory defect
HP:0002094	Dyspnea
HP:0002103	Abnormal pleura morphology
HP:0002205	Recurrent respiratory infections
HP:0002239	Gastrointestinal hemorrhage
HP:0002718	Recurrent bacterial infections

GWAS associations

140 associations (top):

Study	Trait	p-value
GCST000461_3	Hippocampal atrophy	3.000000e-06
GCST000463_1	Acute lymphoblastic leukemia (childhood)	1.000000e-19
GCST000464_6	Acute lymphoblastic leukemia (childhood)	8.000000e-11
GCST000503_9	Mean corpuscular volume	5.000000e-13
GCST000507_3	Systemic lupus erythematosus	3.000000e-23
GCST000879_33	Crohn’s disease	1.000000e-08
GCST001320_14	Acute lymphoblastic leukemia (childhood)	9.000000e-11
GCST001320_17	Acute lymphoblastic leukemia (childhood)	8.000000e-13
GCST001725_93	Inflammatory bowel disease	7.000000e-15
GCST001765_4	Red blood cell traits	2.000000e-13
GCST001795_17	Systemic lupus erythematosus	6.000000e-06
GCST001848_215	IgG glycosylation	1.000000e-08
GCST001848_221	IgG glycosylation	8.000000e-09
GCST001848_229	IgG glycosylation	8.000000e-12
GCST001848_303	IgG glycosylation	2.000000e-13
GCST001848_310	IgG glycosylation	2.000000e-07
GCST001848_458	IgG glycosylation	7.000000e-06
GCST001848_586	IgG glycosylation	5.000000e-07
GCST001848_688	IgG glycosylation	7.000000e-11
GCST001912_1	Acute lymphoblastic leukemia (childhood)	2.000000e-29
GCST002158_6	Acute lymphoblastic leukemia (B-cell precursor)	3.000000e-33
GCST002223_37	HDL cholesterol	1.000000e-08
GCST002657_2	Acute lymphoblastic leukemia (childhood)	7.000000e-09
GCST002726_24	Glucose homeostasis traits	7.000000e-06
GCST002779_1	Cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with severe mucosal involvement	8.000000e-11
GCST003155_6	Systemic lupus erythematosus	6.000000e-14
GCST003156_3	Systemic lupus erythematosus	4.000000e-07
GCST003599_8	Systemic lupus erythematosus	2.000000e-16
GCST003622_49	Systemic lupus erythematosus	3.000000e-06
GCST003995_13	Tonsillectomy	1.000000e-11

EFO canonical traits (44, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy
EFO:0005193	serum IgG glycosylation measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006831	acute insulin response measurement
EFO:0006997	response to cold medicine
EFO:0007924	tonsillectomy risk measurement
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007990	neutrophil percentage of leukocytes
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008423	IgG monogalactosylation measurement
EFO:0008424	IgG digalactosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008426	IgG bisecting N-acetyl glucosamine measurement
EFO:0008428	IgG sialylation measurement
EFO:0008429	IgG disialylation measurement
EFO:0008473	insulin response measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0005128	albumin:globulin ratio measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001327	Autoimmune Diseases	C20.111
D013724	Teratoma	C04.557.465.910

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4296103 (PROTEIN COMPLEX), CHEMBL4630739 (PROTEIN-PROTEIN INTERACTION), CHEMBL4739685 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 19,910 (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
CHEMBL3989927	IBERDOMIDE	3	1,300

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 15 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
IKZF1 Deletion	Methotrexate + Daunorubicin + Cytarabine + Fludarabine + Imatinib	B-lymphoblastic Leukemia/lymphoma	Sensitivity/Response	CIViC B	EID7366

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

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 23 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	EC50	1	nM	IBERDOMIDE
7.62	EC50	24	nM	POMALIDOMIDE
7.46	EC50	35	nM	CHEMBL6074489
7.41	EC50	39	nM	CHEMBL5094460
7.37	EC50	43	nM	CHEMBL5086132
7.30	AC50	50	nM	POMALIDOMIDE
7.29	EC50	51	nM	CHEMBL5920458
7.18	AC50	66	nM	CHEMBL5422767
7.17	EC50	67	nM	LENALIDOMIDE
6.92	EC50	120	nM	CHEMBL5827740
6.92	EC50	120	nM	CHEMBL5531974
6.89	AC50	130	nM	CHEMBL5399912
6.85	EC50	140	nM	CHEMBL5088556
6.66	EC50	220	nM	CHEMBL5072327
6.60	EC50	250	nM	CHEMBL5088587
6.54	EC50	290	nM	CHEMBL6028820
6.50	EC50	320	nM	CHEMBL5077358
6.24	EC50	570	nM	CHEMBL5919701
6.20	EC50	630	nM	CHEMBL5827740
6.19	EC50	650	nM	CHEMBL6078004
5.62	EC50	2370	nM	CHEMBL5914566
5.28	EC50	5200	nM	CHEMBL5893219
5.12	AC50	7600	nM	CHEMBL5420495

PubChem BioAssay actives

3 with measured affinity, of 290 total; 3 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
(3S)-3-[7-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1387871: Induction of cereblon-mediated ikaros degradation in human DF15 cells expressing ePL-tagged ikaros after 4 hrs by luminometric analysis	ec50	0.0010	uM
Pomalidomide	1387871: Induction of cereblon-mediated ikaros degradation in human DF15 cells expressing ePL-tagged ikaros after 4 hrs by luminometric analysis	ec50	0.0240	uM
Lenalidomide	1387871: Induction of cereblon-mediated ikaros degradation in human DF15 cells expressing ePL-tagged ikaros after 4 hrs by luminometric analysis	ec50	0.0670	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Valproic Acid	increases methylation, increases expression	3
Nickel	increases expression	2
afuresertib	affects cotreatment, decreases expression, increases reaction	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases expression	1
indeno(1,2,3-cd)pyrene	increases expression, increases reaction	1
tamibarotene	affects expression	1
5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3’,5’-monophosphorothioate	decreases activity, decreases reaction	1
azoxystrobin	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
4,5,6,7-tetrabromobenzotriazole	decreases activity, decreases reaction	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pomalidomide	affects cotreatment, decreases expression, increases reaction	1
pyrimidifen	decreases expression	1
2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole	decreases activity, decreases reaction	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	decreases methylation	1
gardiquimod	increases expression, decreases reaction	1
picoxystrobin	decreases expression	1
Bortezomib	decreases expression	1
Acetaminophen	increases expression	1
Ascorbic Acid	decreases activity, decreases reaction	1
Cadmium	increases abundance, increases expression	1
Calcitriol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression, increases reaction	1

ChEMBL screening assays

106 unique, capped per target: 105 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4219434	Binding	Induction of cereblon-mediated ikaros degradation in human DF15 cells expressing ePL-tagged ikaros after 4 hrs by luminometric analysis	A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. — J Med Chem
CHEMBL5346088	Functional	In vivo protac activity at CRBN/IKZF1 in CB17-SCID mouse xenografted with human TMD8 cells assessed as degradation of IKZF1 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

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3D8	SEES3-1V human IKZF1, clone1	Embryonic stem cell	Male
CVCL_A3D9	SEES3-1V human IKZF1, clone2	Embryonic stem cell	Male
CVCL_A3E0	SEES3-1V human IKZF1, clone3	Embryonic stem cell	Male
CVCL_B0Z7	Abcam Jurkat IKZF1 KO	Cancer cell line	Male
CVCL_RP57	B3 HA-Ikaros-IRES-GFP	Cancer cell line
CVCL_RP58	B3 HA-159A Ikaros-IRES-GFP	Cancer cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001658	PHASE4	COMPLETED	Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections
NCT00820469	PHASE4	COMPLETED	Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab
NCT00862693	PHASE4	UNKNOWN	Calcitriol in the Treatment of Immunoglobulin A Nephropathy
NCT01065285	PHASE4	COMPLETED	Vaccination Against Influenza in Autoimmune Diseases
NCT04015596	PHASE4	TERMINATED	Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS
NCT04127747	PHASE4	UNKNOWN	Efficacy of Individualized Rituximab in Maintaining Remission of Moderate and Severe Systemic Lupus Erythematosus
NCT04297592	PHASE4	ENROLLING_BY_INVITATION	Antibiotic Prophylaxis in High-Risk Arthroplasty Patients
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT06723548	PHASE4	NOT_YET_RECRUITING	Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis
NCT06964269	PHASE4	RECRUITING	Use of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease
NCT00114348	PHASE4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00192673	PHASE4	UNKNOWN	Poly(Ethylene Glycol)(PEG)-Asparaginase During Two Treatment Courses
NCT00222612	PHASE4	UNKNOWN	Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
NCT00411541	PHASE4	COMPLETED	Pulses of Vincristine and Dexamethasone in BFM Protocols for Children With Acute Lymphoblastic Leukemia
NCT00494897	PHASE4	COMPLETED	PETHEMA LAL-RI/96: Treatment for Patients With Standard Risk Acute Lymphoblastic Leukemia
NCT00526175	PHASE4	COMPLETED	LAL-BR/2001: Study Treatment to Low Risk ALL
NCT00526305	PHASE4	COMPLETED	LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive
NCT00526409	PHASE4	COMPLETED	LAL-AR-N-2005:Study Treatment for Children High Risk Acute Lymphoblastic Leukemia
NCT00576472	PHASE4	COMPLETED	Learning Impairments Among Survivors of Childhood Cancer
NCT00797810	PHASE4	UNKNOWN	Intensification Therapy of Mature B-ALL, Burkitt and Burkitt Like and Other High Grade Non-Hodgkin’s Lymphoma in Adults
NCT00846703	PHASE4	UNKNOWN	The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia
NCT00853008	PHASE4	COMPLETED	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
NCT01358201	PHASE4	UNKNOWN	PETHEMA LAL-07FRAIL: All Treatment In Fragile Patients Ph’ Negative Over 55 Years
NCT01358253	PHASE4	COMPLETED	Rituximab Plus Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia
NCT01366898	PHASE4	UNKNOWN	Protocol For the Treatment Acute Lymphoblastic Leukemia With Ph ‘Negative in Elderly Patients (> 55 Years)
NCT01735955	PHASE4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01873807	PHASE4	UNKNOWN	HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL
NCT01906671	PHASE4	UNKNOWN	Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid
NCT02447718	PHASE4	COMPLETED	Vaccinating Children After Chemotherapy
NCT02670564	PHASE4	UNKNOWN	ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)
NCT02894645	PHASE4	UNKNOWN	Malaysia-Singapore Acute Lymphoblastic Leukemia 2010 Study
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT02953730	PHASE4	COMPLETED	The Study on the Pharmacokinetics of PEG-rhG-CSF in Children and Adolescents
NCT03677596	PHASE4	COMPLETED	A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
NCT03920813	PHASE4	UNKNOWN	Determinants of Mercaptopurine Toxicity in Paediatric Acute Lymphoblastic Leukemia Maintenance Therapy
NCT05133310	PHASE4	UNKNOWN	Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia
NCT05687032	PHASE4	COMPLETED	A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
NCT06289673	PHASE4	RECRUITING	Identification of Necessary Information for Treatment Induction in Newly Diagnosed Acute Lymphoblastic Leukemia/Lymphoma
NCT06918054	PHASE4	RECRUITING	Hepatoprotective for Children and Adolescent With Acute Lymphoblastic Leukemia
NCT06918080	PHASE4	ACTIVE_NOT_RECRUITING	Hepatoprotective Measures for Children at High Risk of NAFLD