IKZF2

Summary

IKZF2 (IKAROS family zinc finger 2, HGNC:13177) is a protein-coding gene on chromosome 2q34, encoding Zinc finger protein Helios (Q9UKS7). Transcription factor, which stabilizes the noninflammatory phenotype of regulatory T cells (Tregs).

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 protein forms homo- or hetero-dimers with other Ikaros family members, and is thought to function predominantly in early hematopoietic development. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined.

Source: NCBI Gene 22807 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Strong, GenCC) — +5 more curated relationships
• GWAS associations: 29
• Clinical variants (ClinVar): 103 total — 5 pathogenic
• Phenotypes (HPO): 112
• Druggable target: yes
• MANE Select transcript: NM_001387220

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13177
Approved symbol	IKZF2
Name	IKAROS family zinc finger 2
Location	2q34
Locus type	gene with protein product
Status	Approved
Aliases	Helios
Ensembl gene	ENSG00000030419
Ensembl biotype	protein_coding
OMIM	606234
Entrez	22807

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron

ENST00000342002, ENST00000374319, ENST00000374326, ENST00000412444, ENST00000431520, ENST00000433134, ENST00000434687, ENST00000439848, ENST00000442445, ENST00000451136, ENST00000452786, ENST00000453575, ENST00000457361, ENST00000484040, ENST00000852782, ENST00000852783, ENST00000852784, ENST00000852785, ENST00000852786, ENST00000852787, ENST00000852788, ENST00000852789, ENST00000852790, ENST00000852791, ENST00000852792, ENST00000969329, ENST00000969330, ENST00000969331

RefSeq mRNA: 7 — MANE Select: NM_001387220 NM_001079526, NM_001371274, NM_001371275, NM_001371276, NM_001371277, NM_001387220, NM_016260

CCDS: CCDS2395, CCDS46507

Canonical transcript exons

ENST00000434687 — 9 exons

Exon	Start	End
ENSE00001422730	213150144	213150247
ENSE00003480856	213021993	213022130
ENSE00003501921	213056833	213057099
ENSE00003521073	213013791	213013934
ENSE00003618845	213049713	213049880
ENSE00003722157	213147708	213147812
ENSE00003725169	213148596	213148644
ENSE00003918220	213151413	213151612
ENSE00003919292	212999698	213008084

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0021 / max 291.8679, expressed in 1235 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33533	1.9571	644
33537	1.5773	589
33534	0.6984	253
33532	0.6441	246
33540	0.5992	326
33536	0.4165	153
33530	0.3427	93
33543	0.2044	75
33535	0.1706	68
33541	0.1666	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.94	gold quality
palpebral conjunctiva	UBERON:0001812	95.87	gold quality
amniotic fluid	UBERON:0000173	94.11	gold quality
pharyngeal mucosa	UBERON:0000355	94.00	gold quality
oral cavity	UBERON:0000167	93.94	gold quality
esophagus squamous epithelium	UBERON:0006920	93.70	gold quality
oviduct epithelium	UBERON:0004804	92.19	gold quality
gingival epithelium	UBERON:0001949	92.13	gold quality
gingiva	UBERON:0001828	92.10	gold quality
lower esophagus mucosa	UBERON:0035834	90.26	gold quality
epithelial cell of pancreas	CL:0000083	89.77	silver quality
mucosa of paranasal sinus	UBERON:0005030	89.28	gold quality
epithelium of nasopharynx	UBERON:0001951	89.27	gold quality
upper leg skin	UBERON:0004262	88.89	gold quality
bronchial epithelial cell	CL:0002328	88.17	gold quality
bronchus	UBERON:0002185	87.84	gold quality
esophagus mucosa	UBERON:0002469	87.82	gold quality
upper arm skin	UBERON:0004263	86.18	silver quality
tonsil	UBERON:0002372	85.36	gold quality
superior surface of tongue	UBERON:0007371	84.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.67	gold quality
nasal cavity mucosa	UBERON:0001826	83.64	gold quality
mouth mucosa	UBERON:0003729	83.03	gold quality
nasal cavity epithelium	UBERON:0005384	82.95	gold quality
corpus epididymis	UBERON:0004359	82.89	gold quality
vagina	UBERON:0000996	82.59	gold quality
tongue	UBERON:0001723	82.59	gold quality
mammalian vulva	UBERON:0000997	81.90	gold quality
corpus callosum	UBERON:0002336	81.72	gold quality
minor salivary gland	UBERON:0001830	81.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	43.53
E-ANND-3	yes	6.74
E-ENAD-27	no	3.27

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
FOXP3
IL2	Activation
IL2RA
INPP5D
LNPEP	Activation

JASPAR motifs

Motif	Name	Family
MA2326.1	IKZF2	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:10978333

Upstream regulators (CollecTRI, top): FOXO3, FOXP3

miRNA regulators (miRDB)

484 targeting IKZF2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-8485	100.00	77.57	4731
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-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248

Literature-anchored findings (GeneRIF, showing 40)

• Novel short isoforms of Helios are overexpressed in a patient with T-cell acute lymphoblastic leukemia and may contribute to the development of T-cell malignancies. Data for unaltered Helios indicates tumor suppressor function. (PMID:11937265)
• suggest a critical role for Helios in the mechanism of leukemogenesis (PMID:17297655)
• 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)
• found that suppression of Helios message in CD4(+)CD25(+) T cells significantly attenuates their suppressive function. (PMID:20226531)
• 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)
• Expanded peripheral FoxP3+ Tregs in untreated renal cell carcinoma patients co-express Helios. Interestingly, IL-2 administration results in expansion of FoxP3+Helios+ natural Tregs (nTregs) significantly more than FoxP3+Helios- iTregs. (PMID:21570917)
• Data found that Helios-negative T cells are enriched for naive T cell phenotypes and vice versa. Moreover, Helios can be induced during T cell activation and proliferation, but regresses in the same cells under resting conditions. (PMID:21918685)
• Presence of Helios-positive regulatory T (Treg) cells may maintain susceptibility to helminth infection on the C57BL/6 mouse background. (PMID:22753928)
• Although Ikaros and Helios belong to the same family with similar structure of zinc fingers, their isoforms have different expression profiles, specific genetic alterations, and different clinical relevance in patients with leukemia. (PMID:22931634)
• Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus. (PMID:23264341)
• Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans. (PMID:23359504)
• A differential role for monocyte subsets in control of Helios(+/-) Treg development that is mediated by distinct inflammatory cytokines. (PMID:23365462)
• large number of ex vivo expanded functional Treg can be obtained from long-term T1D patients, although fewer expanded Treg expressed a high level of Helios (PMID:23409157)
• Ectopic expression of ATL-type Helios isoform as well as knockdown of normal Helios or Ikaros promoted T-cell growth. (PMID:23600753)
• expression is not affected in diGeorge syndrome (PMID:25008482)
• Forkhead box protein 3(+) regulatory T cells and Helios(+) subset in perinatally acquired HIV. (PMID:25425428)
• The immunosuppressive enzyme IL4I1 expressed differentially in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells. (PMID:25446972)
• Helios could be considered a more reliable marker for distinguishing thymic derived Regulatory T (tTreg) cells or peripherally induced Treg cells than Nrp1. (PMID:25586548)
• The results show that high vs. low expression of Nrp-1 or Helios does not unequivocally identify Treg clones of thymic or peripheral origin. (PMID:26495986)
• 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)
• High expression of TIGIT and Helios identifies CD4+ T cells with impaired immunological functions, primarily among patients with an advanced stage of Sezary syndrome. (PMID:27592800)
• revealed more than 170 NFAT-associated proteins, half of which are involved in transcriptional regulation. Among them are many hitherto unknown interaction partners of NFATc1 and NFATc2 in T cells, such as Raptor, CHEK1, CREB1, RUNX1, SATB1, Ikaros, and Helios. (PMID:27637333)
• mRNA expression of Helios was decreased in CD4+ T cells from patients with acute coronary syndrome. (PMID:29259350)
• these data strongly imply the physiological importance of Helios expression in Tregs, and suggest that the manipulation of Helios may serve as a novel strategy for cancer immunotherapy. (PMID:29455107)
• Results indicate that downregulation of Helios mRNA, protein expression and signaling may modulate the development of neurological disorders in children with autism spectrum disorder (ASD). Results provide evidence that immune dysfunction is associated with downregulation of Helios expression in children with ASD. (PMID:29698674)
• The results suggested that increased methylation of Foxp3 Treg-specific demethylated region sequence and altered Helios gene expression in peripheral whole blood may have a role in the pathogenesis of rheumatoid arthritis via their effects on Regulatory T cell stability. (PMID:29851536)
• Helios mRNA is down-regulated in Treg cells of patients with hypertension. (PMID:30074152)
• the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3’ untranslated region of Foxp3 and Helios mRNAs in long-term culture. (PMID:30104243)
• This work demonstrates abnormal changes in Helios(+) Tregs and soluble GITR in myasthenia gravis, as well as direct regulation of Helios by GITR in the context of Tregulatory cells. (PMID:31118027)
• The transcription factor Helios, a member of the Ikaros transcription factor family, is expressed in 60-70% of Treg cells in both mouse and man, and is believed to be a marker of tTreg cells. (PMID:31517385)
• The results reveal important roles for Helios in enhancing preferential fetal Treg differentiation and fine-tuning eventual Treg function. (PMID:31757834)
• Coexpression of FOXP3 and a Helios isoform enhances the effectiveness of human engineered regulatory T cells. (PMID:32259202)
• The correlation of helios and neuropilin-1 frequencies with parkinson disease severity. (PMID:32305590)
• RNA-Binding Protein ZFP36L2 Downregulates Helios Expression and Suppresses the Function of Regulatory T Cells. (PMID:32655569)
• Potential therapeutic effects of interleukin-35 on the differentiation of naive T cells into Helios(+)Foxp3(+) Tregs in clinical and experimental acute respiratory distress syndrome. (PMID:33494935)
• Helios-expressing CD8(+) T cells are decreased in patients with systemic lupus erythematosus. (PMID:33715497)
• Differences in Maturation Status and Immune Phenotypes of Circulating Helios(+) and Helios(-) Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals. (PMID:34054801)
• Coexpression of Helios in Foxp3(+) Regulatory T Cells and Its Role in Human Disease. (PMID:34257746)
• Helios is a marker, not a driver, of human Treg stability. (PMID:34561855)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ikzf2	ENSDARG00000069111
mus_musculus	Ikzf2	ENSMUSG00000025997
rattus_norvegicus	Ikzf2	ENSRNOG00000027430
drosophila_melanogaster	CG14442	FBGN0029893
drosophila_melanogaster	CG14440	FBGN0029894

Paralogs (11): ZNF821 (ENSG00000102984), ZNF639 (ENSG00000121864), IKZF4 (ENSG00000123411), ZNF382 (ENSG00000161298), IKZF3 (ENSG00000161405), ZNF613 (ENSG00000176024), IKZF1 (ENSG00000185811), ZNF567 (ENSG00000189042), ZNF649 (ENSG00000198093), ZNF564 (ENSG00000249709), ZNF350 (ENSG00000256683)

Protein

Protein identifiers

Zinc finger protein Helios — Q9UKS7 (reviewed: Q9UKS7)

Alternative names: Ikaros family zinc finger protein 2

All UniProt accessions (7): A0A0A0MSL2, A0A0A0MT14, B4DWF2, Q9UKS7, E7EPU0, E7ES26, E7EUI1

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor, which stabilizes the noninflammatory phenotype of regulatory T cells (Tregs). May possibly act via STAT5-mediated signaling. Binds IL2 promoter and represses its transcription, possibly by epigenetic silencing, inducing deacetylation of core histones in the IL2 promoter. In Tregs, required for FOXP3 recruitment to the IL2 promoter. Required for outer hair cells maturation and, consequently, for hearing.

Subunit / interactions. Can form homodimers. Interacts with IKZF1 and IKZF3. Interacts with IKZF4. Interacts with IKZF5. Interacts with HDAC1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in various types of T cells, including developping thymocytes, activated T cells and regulatory T cells. Expressed in mucosal-associated invariant T (MAIT) cells both during their thymic development and their activation in the periphery.

Disease relevance. Immunodysregulation with variable immunodeficiency and autoimmunity (IMDIA) [MIM:621233] An immunologic disorder presenting with variable manifestations. Some patients have immunodeficiency with lymphopenia and hypogammaglobulinemia, recurrent respiratory infections, and chronic fungal or viral infections. Other patients have autoimmunity, autoinflammation, and lymphoproliferation. Additional variable features include systemic lupus erythematosus and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. IMDIA is inherited as an autosomal dominant or autosomal recessive condition. The disease is caused by variants affecting the gene represented in this entry. ICHAD syndrome (ICHAD) [MIM:621234] An autosomal dominant syndrome characterized by a core phenotype consisting of T-cell lymphopenia, recurrent respiratory infections, craniofacial anomalies, cleft palate, sensorineural hearing impairment, athelia, and developmental delay. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (8)

UniProt ID	Names	Canonical?
Q9UKS7-1	1	yes
Q9UKS7-2	2, Helios 1v
Q9UKS7-3	3, Helios del(Ex3,4)
Q9UKS7-4	4, Helios del(Ex6)v
Q9UKS7-5	5, Helios 1+2a,2b, Helios 1v+2a, Helios del(Ex3)+2a
Q9UKS7-6	6, Helios 1+5a, Helios 1+5a,5b
Q9UKS7-7	7, Helios del(Ex5)v
Q9UKS7-8	8, Helios S

RefSeq proteins (7): NP_001072994, NP_001358203, NP_001358204, NP_001358205, NP_001358206, NP_001374149, NP_057344 (=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 (46 total): sequence variant 12, splice variant 10, zinc finger region 6, cross-link 6, modified residue 4, compositionally biased region 3, sequence conflict 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9OHQ	X-RAY DIFFRACTION	1.6
9DOM	X-RAY DIFFRACTION	1.69
9O91	X-RAY DIFFRACTION	1.86
9OHR	X-RAY DIFFRACTION	2.34
9Q22	X-RAY DIFFRACTION	3.41
8DEY	X-RAY DIFFRACTION	3.7
7LPS	X-RAY DIFFRACTION	3.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKS7-F1	52.62	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 (10): 56, 78, 79, 288, 95, 442, 448, 95, 95, 95

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 496 (showing top): FREAC2_01, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, AREB6_03, AP4_Q6, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, FOXO4_01, FOXO1_01, CAGCTG_AP4_Q5, FOXD3_01, EVI1_05, GATA3_01, IRF1_Q6

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), sensory perception of sound (GO:0007605), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

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
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
sensory perception of mechanical stimulus	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	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
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
protein binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKZF2	FOXP3	Q9BZS1	602
IKZF2	MSI2	Q96DH6	558
IKZF2	IL2RA	P01589	556
IKZF2	TNFRSF18	Q9Y5U5	545
IKZF2	CTLA4	P16410	537
IKZF2	RELA	Q04206	530
IKZF2	CD4	P01730	505
IKZF2	NCAM1	P13591	500
IKZF2	TIGIT	Q495A1	500
IKZF2	KAT5	Q92993	492
IKZF2	LAG3	P18627	489
IKZF2	GATA3	P23771	488
IKZF2	TBX21	Q9UL17	474
IKZF2	TNFRSF4	P43489	468
IKZF2	SKIDA1	Q1XH10	464

IntAct

28 interactions, top by confidence:

A	B	Type	Score
IKZF2	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
Hoxa1	IKZF2	psi-mi:“MI:0915”(physical association)	0.570
AQP1	IKZF2	psi-mi:“MI:0915”(physical association)	0.560
CTBP2	IKZF2	psi-mi:“MI:0915”(physical association)	0.560
IKZF2	LONRF1	psi-mi:“MI:0915”(physical association)	0.560
IKZF2	CTBP2	psi-mi:“MI:0915”(physical association)	0.560
IKZF2	AQP1	psi-mi:“MI:0915”(physical association)	0.560
LONRF1	IKZF2	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
IKZF2	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
IKZF2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
NOTCH1	CNOT1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MYC	PDZD2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
IKZF5	PEX14	psi-mi:“MI:0914”(association)	0.350
IKZF1	MTA2	psi-mi:“MI:0914”(association)	0.350
IKZF1	POTEF	psi-mi:“MI:0914”(association)	0.350
IKZF1	HSPA1L	psi-mi:“MI:0914”(association)	0.350
HDAC1	KPNA3	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): IKZF2 (Two-hybrid), IKZF2 (Two-hybrid), LONRF1 (Two-hybrid), IKZF2 (PCA), Hoxa1 (Affinity Capture-Western), IKZF2 (Affinity Capture-Western), IKZF2 (Affinity Capture-Western), IKZF2 (Affinity Capture-MS), IKZF2 (Affinity Capture-MS), IKZF2 (Affinity Capture-MS), IKZF2 (Affinity Capture-MS), IKZF2 (Two-hybrid), HDAC4 (Reconstituted Complex), SIN3A (Affinity Capture-Western), SIN3B (Affinity Capture-Western)

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

1 interactions.

A	Effect	B	Mechanism
IKZF2	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	68
Likely benign	10
Benign	10

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3903426	IKZF2, TYR200TER	Pathogenic
3903427	I325V	Pathogenic
3903428	IKZF2, ARG291TER (rs146574423)	Pathogenic
3903429	IKZF2, ARG106TRP	Pathogenic
3903430	IKZF2, 20-KB DUP	Pathogenic

SpliceAI

2836 predictions. Top by Δscore:

Variant	Effect	Δscore
2:213008111:G:GC	acceptor_gain	1.0000
2:213013935:C:CC	acceptor_gain	1.0000
2:213021989:CCAC:C	donor_loss	1.0000
2:213021992:C:CA	donor_loss	1.0000
2:213022011:G:A	donor_gain	1.0000
2:213022126:ACCCA:A	acceptor_gain	1.0000
2:213022127:CCCA:C	acceptor_gain	1.0000
2:213022127:CCCAC:C	acceptor_gain	1.0000
2:213022128:CCA:C	acceptor_gain	1.0000
2:213022128:CCAC:C	acceptor_gain	1.0000
2:213022129:CA:C	acceptor_gain	1.0000
2:213022129:CAC:C	acceptor_gain	1.0000
2:213022130:ACTG:A	acceptor_loss	1.0000
2:213022131:C:CA	acceptor_loss	1.0000
2:213022131:C:CC	acceptor_gain	1.0000
2:213049706:CACTT:C	donor_loss	1.0000
2:213049707:ACTT:A	donor_loss	1.0000
2:213049708:CTTAC:C	donor_loss	1.0000
2:213049709:TTA:T	donor_loss	1.0000
2:213049710:T:TC	donor_loss	1.0000
2:213049711:A:AC	donor_gain	1.0000
2:213049712:C:CA	donor_loss	1.0000
2:213049712:C:CC	donor_gain	1.0000
2:213049880:CCTGC:C	acceptor_loss	1.0000
2:213049881:C:CA	acceptor_loss	1.0000
2:213049884:CAG:C	acceptor_gain	1.0000
2:213049885:A:T	acceptor_gain	1.0000
2:213049886:G:GC	acceptor_gain	1.0000
2:213056626:T:TA	donor_gain	1.0000
2:213056956:T:A	donor_gain	1.0000

AlphaMissense

3556 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:213007431:A:G	C504R	1.000
2:213007440:A:G	C501R	1.000
2:213007515:A:G	C476R	1.000
2:213007524:A:G	C473R	1.000
2:213022102:A:C	C201W	1.000
2:213022103:C:T	C201Y	1.000
2:213022104:A:G	C201R	1.000
2:213022113:A:G	C198R	1.000
2:213049727:A:G	L187P	1.000
2:213049729:G:C	H186Q	1.000
2:213049729:G:T	H186Q	1.000
2:213049731:G:C	H186D	1.000
2:213049758:A:G	C177R	1.000
2:213049768:A:C	C173W	1.000
2:213049769:C:T	C173Y	1.000
2:213049770:A:G	C173R	1.000
2:213049777:A:C	C170W	1.000
2:213049779:A:G	C170R	1.000
2:213049813:G:C	H158Q	1.000
2:213049813:G:T	H158Q	1.000
2:213049814:T:G	H158P	1.000
2:213049815:G:C	H158D	1.000
2:213049815:G:T	H158N	1.000
2:213049823:A:G	L155P	1.000
2:213049840:A:C	F149L	1.000
2:213049840:A:T	F149L	1.000
2:213049841:A:G	F149S	1.000
2:213049842:A:G	F149L	1.000
2:213049842:A:T	F149I	1.000
2:213049854:A:G	C145R	1.000

dbSNP variants (sampled 300 via entrez): RS1000035391 (2:213018048 C>G), RS1000040563 (2:213079093 A>T), RS1000068776 (2:213064169 G>T), RS1000109957 (2:213017817 T>C), RS1000125179 (2:213101431 T>A), RS1000136835 (2:213114990 C>T), RS1000139729 (2:213146157 A>G,T), RS1000187268 (2:213076547 A>G), RS1000202551 (2:213116505 C>A,T), RS1000210125 (2:213083293 A>G), RS1000216720 (2:213025416 A>G), RS1000233796 (2:213050231 A>T), RS1000250173 (2:213151788 A>T), RS1000285676 (2:213077688 C>T), RS1000309296 (2:213121943 A>G)

Disease associations

OMIM: gene MIM:606234 | disease phenotypes: MIM:621234, MIM:621233

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Strong	Autosomal dominant
immunodysregulation with variable immunodeficiency and autoimmunity	Strong	Semidominant
ICHAD syndrome	Strong	Autosomal dominant
hearing loss disorder	Limited	Autosomal dominant
immunodeficiency disease	Limited	Autosomal dominant
HELIOS deficiency	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
HELIOS deficiency	Moderate	SD

Mondo (6): ICHAD syndrome (MONDO:0979234), immunodysregulation with variable immunodeficiency and autoimmunity (MONDO:0979233), hearing loss disorder (MONDO:0005365), immunodeficiency disease (MONDO:0021094), HELIOS deficiency (MONDO:0800139), nonsyndromic genetic hearing loss (MONDO:0019497)

Orphanet (1): ICHAD syndrome (Orphanet:699599)

HPO phenotypes

112 total (30 of 112 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000175	Cleft palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000426	Prominent nasal bridge
HP:0000452	Choanal stenosis
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000498	Blepharitis
HP:0000581	Blepharophimosis
HP:0000613	Photophobia
HP:0000637	Long palpebral fissure
HP:0000670	Carious teeth
HP:0000717	Autism
HP:0000817	Reduced eye contact
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0000988	Skin rash
HP:0000992	Cutaneous photosensitivity
HP:0001045	Vitiligo
HP:0001047	Atopic dermatitis
HP:0001263	Global developmental delay
HP:0001344	Absent speech

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000339_7	Eosinophil count	5.000000e-10
GCST003155_44	Systemic lupus erythematosus	1.000000e-13
GCST003156_44	Systemic lupus erythematosus	2.000000e-10
GCST003622_71	Systemic lupus erythematosus	2.000000e-08
GCST003814_6	Selective IgA deficiency	3.000000e-07
GCST004600_177	Eosinophil percentage of white cells	2.000000e-14
GCST004606_51	Eosinophil count	2.000000e-15
GCST004617_72	Eosinophil percentage of granulocytes	2.000000e-13
GCST004623_166	Neutrophil percentage of granulocytes	1.000000e-10
GCST004624_58	Sum eosinophil basophil counts	1.000000e-12
GCST004748_76	Lung cancer	5.000000e-06
GCST004750_101	Squamous cell lung carcinoma	5.000000e-06
GCST005336_4	Systemic sclerosis	1.000000e-06
GCST005975_8	Eosinophil count	6.000000e-19
GCST006065_21	Glaucoma (primary open-angle)	2.000000e-13
GCST006067_2	Glaucoma (primary open-angle)	2.000000e-08
GCST006979_87	Heel bone mineral density	3.000000e-09
GCST007614_39	C-reactive protein levels	2.000000e-11
GCST008747_37	Estimated glomerular filtration rate	9.000000e-06
GCST008747_51	Estimated glomerular filtration rate	4.000000e-07
GCST009391_573	Metabolite levels	5.000000e-06
GCST009391_739	Metabolite levels	6.000000e-06
GCST009597_199	Multiple sclerosis	8.000000e-07
GCST010118_18	Type 2 diabetes	5.000000e-10
GCST90002381_330	Eosinophil count	5.000000e-12
GCST90002381_331	Eosinophil count	2.000000e-27
GCST90002381_332	Eosinophil count	2.000000e-13
GCST90002382_85	Eosinophil percentage of white cells	5.000000e-37
GCST90002382_86	Eosinophil percentage of white cells	1.000000e-12

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0009270	heel bone mineral density
EFO:0004458	C-reactive protein measurement
EFO:0021604	hypoxanthine measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5465255 (SINGLE PROTEIN), CHEMBL5465554 (PROTEIN-PROTEIN INTERACTION)

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

Binding affinities (BindingDB)

33 measured of 37 human assays (37 total across all organisms); most potent 33 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(1’-(4-(difluoromethyl)benzyl)-6- oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1-(4-ethylbenzyl)-7’-oxo-2’,3’,7’,9’- tetrahydro-8’H-spiro[piperidine-4,4’- pyrano[2,3-e]isoindol]-8’- yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1-(4-methylbenzyl)-7’-oxo- 2’,3’,7’,9’-tetrahydro-8’H- spiro[piperidine-4,4’-pyrano[2,3- e]isoindol]-8’-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((1H-indazol-7-yl)methyl)-6- oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((1H-indol-6-yl)methyl)-6-oxo- 6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(1-ethyl-1H-pyrazol-4- yl)benzyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(1H-pyrazol-3-yl)benzyl)-6- oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(1-(oxetan-3-yl)-1H-pyrazol- 4-yl)benzyl)-6-oxo-6,8-dihydro- 2H,7H-spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	55 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(7’-oxo-2’,3’,7’,9’-tetrahydro-8’H- spiro[piperidine-4,4’-pyrano[2,3- e]isoindol]-8’-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
US20250215012, Example A5	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-benzyl-6-oxo-6,8-dihydro- 2H,7H-spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(4-methylbenzyl)-6-oxo-6,8- dihydro-2H,7H-spiro[furo[2,3- e]isoindole-3,4’-piperidin]-7- yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(naphthalen-1-ylmethyl)-6-oxo- 6,8-dihydro-2H,7H-spiro[furo[2,3- e]isoindole-3,4’-piperidin]-7- yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3,5-dimethylbenzyl)-6-oxo-6,8- dihydro-2H,7H-spiro[furo[2,3- e]isoindole-3,4’-piperidin]-7- yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((1H-indazol-4-yl)methyl)-6- oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((1H-indazol-6-yl)methyl)-6- oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((2-methyl-2H-indazol-6- yl)methyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((1H-indol-4-yl)methyl)-6-oxo- 6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(hydroxymethyl)benzyl)-6- oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(1-methyl-1H-pyrazol-4- yl)benzyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(benzofuran-6-ylmethyl)-6-oxo- 6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(6-oxo-1’-((3-oxoisoindolin-5- yl)methyl)-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(1H-1,2,4-triazol-1- yl)benzyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(oxazol-5-yl)benzyl)-6-oxo- 6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-((1H-pyrazol-1- yl)methyl)benzyl)-6-oxo-6,8-dihydro- 2H,7H-spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((6-bromo-1H-indazol-4- yl)methyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((6-chloro-1H-indazol-4- yl)methyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-((1-methyl-1H-indol-6- yl)methyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(6-oxo-1’-((2-oxoindolin-6- yl)methyl)-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(6-oxo-1’-(3-(pyridin-3-yl)benzyl)- 6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(6-oxo-1’-(3-(pyridin-4-yl)benzyl)- 6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
3-(1’-(3-(1-methyl-1H-pyrazol-3- yl)benzyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF
(S)-3-(1’-(3-(1-methyl-1H-pyrazol-4- yl)benzyl)-6-oxo-6,8-dihydro-2H,7H- spiro[furo[2,3-e]isoindole-3,4’- piperidin]-7-yl)piperidine-2,6-dione	IC50	550 nM	US-20250215012: IKZF2 DEGRADERS AND USES THEREOF

ChEMBL bioactivities

56 potent at pChembl≥5 of 59 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	EC50	6	nM	CHEMBL5434155
8.22	EC50	6	nM	CHEMBL5401739
8.22	EC50	6	nM	CHEMBL5436432
8.22	EC50	6	nM	CHEMBL5436826
8.22	EC50	6	nM	CHEMBL5441130
8.22	EC50	6	nM	CHEMBL5427472
8.22	EC50	6	nM	CHEMBL5400246
8.22	EC50	6	nM	CHEMBL5395344
8.22	EC50	6	nM	CHEMBL5426981
8.22	EC50	6	nM	CHEMBL5424205
8.22	AC50	6	nM	CHEMBL5409278
8.05	AC50	9	nM	CHEMBL5415405
7.92	AC50	12	nM	CHEMBL5424623
7.85	AC50	14	nM	CHEMBL5418048
7.77	AC50	17	nM	CHEMBL5416455
7.72	AC50	19	nM	CHEMBL5434993
7.70	AC50	20	nM	CHEMBL5426577
7.62	AC50	24	nM	CHEMBL5429255
7.62	EC50	24	nM	CHEMBL6028820
7.60	AC50	25	nM	CHEMBL5431857
7.54	EC50	29	nM	CHEMBL5764874
7.44	EC50	36	nM	CHEMBL5877025
7.42	AC50	38	nM	CHEMBL5419673
7.37	EC50	43	nM	CHEMBL5859132
7.31	EC50	49	nM	CHEMBL5920458
7.19	AC50	64	nM	CHEMBL5418823
7.18	EC50	66	nM	CHEMBL5919701
7.12	AC50	75	nM	CHEMBL5399912
7.10	AC50	79	nM	CHEMBL5403711
7.05	AC50	89	nM	CHEMBL5411465
7.04	AC50	92	nM	CHEMBL5408832
7.00	EC50	100	nM	CHEMBL5956806
6.99	EC50	103	nM	CHEMBL6019847
6.96	AC50	110	nM	CHEMBL5414298
6.95	EC50	113	nM	CHEMBL6019847
6.85	AC50	140	nM	CHEMBL5438898
6.82	EC50	150	nM	CHEMBL5893219
6.74	EC50	183	nM	CHEMBL5778110
6.70	AC50	200	nM	CHEMBL5422767
6.64	EC50	230	nM	CHEMBL5827740
6.64	EC50	230	nM	CHEMBL5816828
6.58	AC50	260	nM	CHEMBL5430598
6.39	EC50	410	nM	CHEMBL5741758
6.35	EC50	450	nM	CHEMBL5743550
6.25	AC50	560	nM	CHEMBL5420495
6.17	EC50	670	nM	CHEMBL5827740
6.14	EC50	730	nM	CHEMBL5813805
6.03	EC50	940	nM	CHEMBL5885806
6.00	EC50	990	nM	CHEMBL6002378
5.80	EC50	1570	nM	CHEMBL5914566

PubChem BioAssay actives

10 with measured affinity, of 96 total; 10 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
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-8-methoxy-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-6-methoxy-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-(trifluoromethoxy)-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-(trifluoromethyl)-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-methyl-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
7-bromo-N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
6,8-dibromo-N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-5-methoxy-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-methoxy-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM
6-bromo-N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-8-methoxy-2H-chromene-3-carboxamide	2025216: Protac activity at CRBN/IKZF2 (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0060	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	4
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
methylmercuric chloride	decreases expression	2
bisphenol A	affects cotreatment, affects methylation, decreases expression, increases methylation	2
trichostatin A	increases expression	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects expression, affects methylation, increases methylation	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	decreases expression, increases abundance	1
sulforaphane	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
antimonite	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
2,6-dichloro-(1,4)benzoquinone	decreases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5350496	Binding	Induction of IKZF2 degradation in human GripTite 293 MSR cells	Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV67	HEK293 eGFP-IKZF2	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss