IL2

gene
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Also known as IL-2TCGF

Summary

IL2 (interleukin 2, HGNC:6001) is a protein-coding gene on chromosome 4q27, encoding Interleukin-2 (P60568). Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance.

This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli.

Source: NCBI Gene 3558 — RefSeq curated summary.

At a glance

  • GWAS associations: 55
  • Clinical variants (ClinVar): 3 total — 2 pathogenic
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000586

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:6001
Approved symbolIL2
Nameinterleukin 2
Location4q27
Locus typegene with protein product
StatusApproved
AliasesIL-2, TCGF
Ensembl geneENSG00000109471
Ensembl biotypeprotein_coding
OMIM147680
Entrez3558

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000226730, ENST00000477645

RefSeq mRNA: 1 — MANE Select: NM_000586 NM_000586

CCDS: CCDS3726

Canonical transcript exons

ENST00000226730 — 4 exons

ExonStartEnd
ENSE00000935280122456144122456203
ENSE00001138256122451470122451862
ENSE00001293064122456294122456725
ENSE00003641080122453710122453853

Expression profiles

Bgee: expression breadth broad, 92 present calls, max score 84.25.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099184.25gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047379.10gold quality
buccal mucosa cellCL:000233668.91gold quality
endometrium epitheliumUBERON:000481159.26gold quality
frontal poleUBERON:000279556.64gold quality
lymph nodeUBERON:000002955.03gold quality
vermiform appendixUBERON:000115454.05gold quality
lower esophagus mucosaUBERON:003583452.98gold quality
small intestine Peyer’s patchUBERON:000345452.02gold quality
granulocyteCL:000009451.98gold quality
caecumUBERON:000115350.95gold quality
small intestineUBERON:000210850.64gold quality
middle frontal gyrusUBERON:000270250.30gold quality
rectumUBERON:000105250.26gold quality
Brodmann (1909) area 10UBERON:001354150.18gold quality
quadriceps femorisUBERON:000137749.95gold quality
metanephric glomerulusUBERON:000473649.61gold quality
Brodmann (1909) area 46UBERON:000648349.30gold quality
vastus lateralisUBERON:000137949.27gold quality
cerebellar vermisUBERON:000472049.25gold quality
cervix squamous epitheliumUBERON:000692249.20gold quality
hair follicleUBERON:000207349.18gold quality
olfactory bulbUBERON:000226448.92gold quality
epithelial cell of pancreasCL:000008348.87gold quality
myocardiumUBERON:000234948.87gold quality
type B pancreatic cellCL:000016948.83gold quality
cardiac muscle of right atriumUBERON:000337948.55gold quality
oviduct epitheliumUBERON:000480448.53gold quality
CA1 field of hippocampusUBERON:000388148.50gold quality
left ventricle myocardiumUBERON:000656648.24gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-HCAD-29no52565.79
E-ANND-3no2.20

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

TargetRegulation
NAB2Activation
TNFSF10Repression

Upstream regulators (CollecTRI, top): AGO1, AGO2, AP1, AR, BACH2, BATF3, BCL11B, BCL3, BCL6, BCL6B, BHLHE40, CEBPB, CREB1, CREB3, CREM, CTBP2, EGR1, EGR4, ELF1, EOMES, ESR1, ETS1, ETS2, FOS, FOSB, FOSL1, FOSL2, FOXC1, FOXK2, FOXN1, FOXO3, FOXP1, FOXP3, GABPA, GFI1, GLI3, HAND1, HAND2, HBP1, HDAC1

miRNA regulators (miRDB)

41 targeting IL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4262100.0073.263931
HSA-MIR-5692A100.0074.406850
HSA-MIR-3163100.0077.238605
HSA-MIR-450A-1-3P100.0069.331837
HSA-MIR-181A-5P99.9972.962995
HSA-MIR-181B-5P99.9972.972996
HSA-MIR-181C-5P99.9972.952996
HSA-MIR-181D-5P99.9973.042997
HSA-MIR-428299.9975.366408
HSA-MIR-186-5P99.9970.833707
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-3065-5P99.9771.563281
HSA-MIR-365899.9673.874379
HSA-MIR-314399.9371.963104
HSA-MIR-449399.9066.48977
HSA-MIR-95-5P99.8972.173973
HSA-MIR-3121-3P99.8271.963630
HSA-MIR-430799.8270.453374
HSA-MIR-3913-5P99.7867.26968
HSA-MIR-190A-5P99.5471.45933
HSA-MIR-190B-5P99.5471.40925
HSA-MIR-7159-5P99.5372.122472
HSA-MIR-54399.5269.032595
HSA-MIR-312299.5066.33821
HSA-MIR-6513-5P99.4367.811071
HSA-MIR-6507-5P99.3670.462524
HSA-MIR-42198.9067.041883
HSA-MIR-374A-3P98.8767.821531
HSA-MIR-4477A98.8369.752952
HSA-MIR-887-5P98.8265.901347

Literature-anchored findings (GeneRIF, showing 40)

  • Primary T lymphocytes that exhibit avid specific melanoma antigen and tumor recognition can be retrovirally transduced, produce IL-2 and grow for over 8 weeks in the absence of IL-2, upon restimulation. (PMID:11714800)
  • kinetic mechanism of basal transcription at the IL-2 promoter using a human in vitro RNA polymerase II transcription system (PMID:11743717)
  • IL-2 plays an important and complex role in the immune system, serving as a growth factor, a differentiation factor, and a regulator of cell death. (PMID:11826762)
  • role in regulation of Toll-like receptor surface expression in human peripheral blood monocytes and B cells (PMID:11841848)
  • Molecular mechanism of NFAT family proteins for differential regulation of the IL-2 and TNF-alpha promoters. (PMID:11911478)
  • recombinant IL-2 treatment decreases P-glycoprotein activity and paclitaxel metabolism (PMID:11914641)
  • The in situ detection of interleukin-2 and interleukin-2 receptor (IL-2R) has been documented in perinatal white matter lesions associated with periventricular leukomalacia. (PMID:11940709)
  • effect of hla-dr matching on acute rejection after heart transplantation influenced by il-2 polymorphism (PMID:11981437)
  • IL-2 directly affects NK cell migratory ability in vitro by rapid and direct down-regulation of chemokine receptor CXCR3 mRNA expression, a decrease associated with a significant reduction in chemotaxis in the presence of IFN-gamma-inducible protein-10. (PMID:12055219)
  • increased HIV replication in the thymus by inducing differentiation and expansion of mature CD27(+) thymocytes expressing CXCR4 or CCR5 (PMID:12072494)
  • B-CLL patients with progressive disease had a significantly increased number of T cells spontaneously producing IL-2, IL-4 and GM-CSF, suggesting a role for T cells in the pathogenesis of B-CLL. (PMID:12144536)
  • Elevated IL-2 and IL-2 receptor serum levels correlated with the severity of cutaneous graft-versus-host disease after bone marrow transplantation, and evidence suggested that both act together in the development of cutaneous GVHD. (PMID:12171778)
  • IL-2 transcription in Jurkat cells is stimulated by a T cell receptor/DOCK2/Rac2 signal transduction pathway (PMID:12176041)
  • The proximal promoter region of the IL-2 gene can assemble into a rotationally and translationally positioned mononucleosome under chromatin reconstitution conditions in vitro and in vivo, maintaining an inactive IL-2 gene in resting T cells. (PMID:12193716)
  • The long-term immunologic effects of IL2 administered to HIV patients, including expansion of T-cell subsets and up-regulation of CD25 expression without increases in expression of the beta and gamma chains of the IL-2 receptor. (PMID:12200381)
  • The spectrin-ankyrin skeleton controls CD45 surface display and interleukin-2 production. (PMID:12354383)
  • mechanisms of IL-2-mediated prosurvival signaling in NK cells via an Akt-dependent pathway regulated by Syk and Rac1 (PMID:12393431)
  • the higher capacity of CTL clones to produce IL-2 on their own seemed to be correlated with the in vivo efficacy for tumor eradication (PMID:12456594)
  • hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation (PMID:12464620)
  • CD56+ NK cells exist in lymph nodes & endogenous T-cell-derived IL-2, acting through the NK high-affinity IL-2 receptor, costimulates them to secrete IFN-gamma. This is the 1st evidence of immunoregulation of innate immune lymphocytes by adaptive ones. (PMID:12480696)
  • A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated production of this protein in Jurkat cells. (PMID:12486027)
  • Nuclear export of NF90 is required for its interleukin-2 mRNA stabilization. (PMID:12504009)
  • IL-2 decreased the expression of ERK2 & increased the expression of ERK3. IL-2 increased the expression of PKCalpha, PKCdelta and PKCepsilon. (PMID:12536241)
  • endothelin-1 (ET-1), interleukin-2 (IL-2) and amino-terminal propeptide type III procollagen (PIII NP) can be used as markers for diagnosis of human cases infected with chronic and acute filariasis (PMID:12557940)
  • IL2 production is increased by FAP48-FKBP complexes (PMID:12604780)
  • no evidence for genetic association conferred by the -384 and 114 IL-2 SNP with respect to susceptibility and severity of rheumatoid arthritis. (PMID:12610796)
  • denaturation transitions in the secondary and tertiary structure of IL-2 suggest intermediates and possible relation to ligand binding and endocytic trafficking (PMID:12717025)
  • One synthetic fragment consisting of amino acids 22-58 contained 100% of the vasopermeability activity of IL-2 and was designated permeability-enhancing peptide (PEP). (PMID:12759392)
  • IL-2 deprivation raises the level of RC3 and other apoptotic factors, which induce apoptosis by increasing the intracellular Ca(2+) concentration (PMID:12808095)
  • IL-2 regulates homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in T cells that have recently exited from the thymus as well as mature naive and memory T cell subsets. (PMID:12816983)
  • Genotype is associated with kidney transplantation rejection, but not with heart transplantation outcome. (PMID:12826155)
  • The mixed leukcyte culture model suggest that allorecognition upregulates IL-2 but not IL-15 expression. (PMID:12826231)
  • In all three groups of patients significant correlation was seen between abundance of IL-2 vs. IL-4, IL-5, IL-10, or TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma (PMID:12851716)
  • IL-2 secretion from rat T9.F glioma cells enhances tumorigenesis when the tumor is implanted in the brain; in contrast, IL-2-secreting T9.F glioma cells are completely rejected when implanted in the periphery, resulting in tumor-specific immunity. (PMID:12864971)
  • expression of alleles of the genes encoding IL-2, IL-3, IL-4, and IL-13 in CD4(+) T cell clones (PMID:12884288)
  • Upon prolonged culture (down phase), human T cells undergo an IL-2-dependent switch from type II signaling to type I signaling cells that renders T cells sensitive to CD95-mediated activation-induced cell death. (PMID:12960316)
  • Number of CD8+/IL-2 cells significantly higher in elderly trained than in elderly untrained. (PMID:14499500)
  • IL-2 activates not only STAT3, STAT5, the phosphatidylinositol 3-kinase pathway, and extracellular signal-regulated kinase-2 pathway, but also STAT4 as in NK cells, and the p38 mitogen-activated protein kinase pathway as in alpha beta T cells. (PMID:14607923)
  • Because IL-2 regulates gene expression through the interactions of transcription factors with IFN-gamma activated sequence and Ets binding site motifs, it is likely that IL-2 influences CD94 gene expression through formation of DNA-protein complexes. (PMID:14607929)
  • The development of breast tumour is associated with an increased expression of IL-2 and this expression also seems to be associated with the malignancy of the tumour. (PMID:14680494)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusIl2ENSMUSG00000027720
rattus_norvegicusIl2ENSRNOG00000017348

Protein

Protein identifiers

Interleukin-2P60568 (reviewed: P60568)

Alternative names: T-cell growth factor

All UniProt accessions (2): P60568, Q0GK43

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance. Binds to a receptor complex composed of either the high-affinity trimeric IL-2R (IL2RA/CD25, IL2RB/CD122 and IL2RG/CD132) or the low-affinity dimeric IL-2R (IL2RB and IL2RG). Interaction with the receptor leads to oligomerization and conformation changes in the IL-2R subunits resulting in downstream signaling starting with phosphorylation of JAK1 and JAK3. In turn, JAK1 and JAK3 phosphorylate the receptor to form a docking site leading to the phosphorylation of several substrates including STAT5. This process leads to activation of several pathways including STAT, phosphoinositide-3-kinase/PI3K and mitogen-activated protein kinase/MAPK pathways. Functions as a T-cell growth factor and can increase NK-cell cytolytic activity as well. Promotes strong proliferation of activated B-cells and subsequently immunoglobulin production. Plays a pivotal role in regulating the adaptive immune system by controlling the survival and proliferation of regulatory T-cells, which are required for the maintenance of immune tolerance. Moreover, participates in the differentiation and homeostasis of effector T-cell subsets, including Th1, Th2, Th17 as well as memory CD8-positive T-cells.

Subcellular location. Secreted.

Disease relevance. A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.

Similarity. Belongs to the IL-2 family.

RefSeq proteins (1): NP_000577* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000779IL-2Family
IPR0090794_helix_cytokine-like_coreHomologous_superfamily
IPR030477IL-2_CSConserved_site

Pfam: PF00715

UniProt features (22 total): helix 12, strand 4, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDBMethodResolution (Å)
8SOZX-RAY DIFFRACTION1.64
8SOWX-RAY DIFFRACTION1.71
7M2GX-RAY DIFFRACTION1.79
4NEJX-RAY DIFFRACTION1.92
4NEMX-RAY DIFFRACTION1.93
1M48X-RAY DIFFRACTION1.95
5LQBX-RAY DIFFRACTION1.95
1M47X-RAY DIFFRACTION1.99
1M49X-RAY DIFFRACTION2
1M4BX-RAY DIFFRACTION2.15
1M4AX-RAY DIFFRACTION2.18
1NBPX-RAY DIFFRACTION2.2
7RA9X-RAY DIFFRACTION2.2
2B5IX-RAY DIFFRACTION2.3
5M5EX-RAY DIFFRACTION2.3
1M4CX-RAY DIFFRACTION2.4
7DR4X-RAY DIFFRACTION2.49
3INKX-RAY DIFFRACTION2.5
1PW6X-RAY DIFFRACTION2.6
7YZJX-RAY DIFFRACTION2.6
7RAAX-RAY DIFFRACTION2.69
1QVNX-RAY DIFFRACTION2.7
5UTZX-RAY DIFFRACTION2.75
1PY2X-RAY DIFFRACTION2.8
1Z92X-RAY DIFFRACTION2.8
6YE3X-RAY DIFFRACTION2.89
9KMCELECTRON MICROSCOPY2.97
2ERJX-RAY DIFFRACTION3
3QB1X-RAY DIFFRACTION3.1
6LX3ELECTRON MICROSCOPY3.15

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P60568-F184.680.60

Antibody-complex structures (SAbDab): 85LQB, 5UTZ, 6YE3, 7DR4, 7YZJ, 8SOW, 8SOZ, 9KMC

Functional residue map

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

Disulfide bonds (1): 78–125

Glycosylation sites (1): 23

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-5673001RAF/MAP kinase cascade
R-HSA-8877330RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
R-HSA-9020558Interleukin-2 signaling
R-HSA-912526Interleukin receptor SHC signaling

MSigDB gene sets: 440 (showing top): PID_SHP2_PATHWAY, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, PID_TELOMERASE_PATHWAY

GO Biological Process (45): adaptive immune response (GO:0002250), leukocyte activation involved in immune response (GO:0002366), positive regulation of immunoglobulin production (GO:0002639), negative regulation of B cell apoptotic process (GO:0002903), transcription by RNA polymerase II (GO:0006366), immune response (GO:0006955), cell adhesion (GO:0007155), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), natural killer cell activation (GO:0030101), T cell differentiation (GO:0030217), positive regulation of cell growth (GO:0030307), positive regulation of B cell proliferation (GO:0030890), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-17 production (GO:0032740), positive regulation of tissue remodeling (GO:0034105), interleukin-2-mediated signaling pathway (GO:0038110), positive regulation of activated T cell proliferation (GO:0042104), negative regulation of apoptotic process (GO:0043066), response to ethanol (GO:0045471), positive regulation of regulatory T cell differentiation (GO:0045591), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of T cell homeostatic proliferation (GO:0046013), positive regulation of isotype switching to IgG isotypes (GO:0048304), negative regulation of lymphocyte proliferation (GO:0050672), negative regulation of inflammatory response (GO:0050728), positive regulation of inflammatory response (GO:0050729), activated T cell proliferation (GO:0050798), positive regulation of dendritic spine development (GO:0060999), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), cell surface receptor signaling pathway via STAT (GO:0097696), positive regulation of plasma cell differentiation (GO:1900100), response to tacrolimus (GO:1901327), negative regulation of T-helper 17 cell differentiation (GO:2000320), regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000561), immune system process (GO:0002376), G protein-coupled receptor signaling pathway (GO:0007186), gene expression (GO:0010467)

GO Molecular Function (8): cytokine activity (GO:0005125), interleukin-2 receptor binding (GO:0005134), growth factor activity (GO:0008083), kinase activator activity (GO:0019209), carbohydrate binding (GO:0030246), kappa-type opioid receptor binding (GO:0031851), glycosphingolipid binding (GO:0043208), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Interleukin-2 family signaling2
MAPK1/MAPK3 signaling1
Transcriptional regulation by RUNX11
Interleukin-3, Interleukin-5 and GM-CSF signaling1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
immune response2
positive regulation of cellular process2
positive regulation of cytokine production2
receptor ligand activity2
binding2
cell activation involved in immune response1
leukocyte activation1
immunoglobulin production1
regulation of immunoglobulin production1
positive regulation of production of molecular mediator of immune response1
B cell apoptotic process1
regulation of B cell apoptotic process1
negative regulation of lymphocyte apoptotic process1
DNA-templated transcription1
immune system process1
response to stimulus1
cellular process1
G protein-coupled receptor signaling pathway1
phospholipase C activator activity1
regulation of biological quality1
cell communication1
signaling1
cell population proliferation1
regulation of cell population proliferation1
lymphocyte activation1
lymphocyte differentiation1
T cell activation1
regulation of cell growth1
cell growth1
positive regulation of growth1
regulation of B cell proliferation1
B cell proliferation1
positive regulation of lymphocyte proliferation1
positive regulation of B cell activation1
type II interferon production1
regulation of type II interferon production1
interleukin-17 production1
regulation of interleukin-17 production1
regulation of tissue remodeling1
tissue remodeling1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

10 interactions, top by confidence:

ABTypeScore
IL2RBIL2psi-mi:“MI:0407”(direct interaction)0.740
IL2IL2RBpsi-mi:“MI:0407”(direct interaction)0.740
IL2IL2RApsi-mi:“MI:0915”(physical association)0.670
IL2IL2RApsi-mi:“MI:0407”(direct interaction)0.670
IL17AIL2psi-mi:“MI:0914”(association)0.530
IL17AATP1A3psi-mi:“MI:0914”(association)0.350

BioGRID (7): IL2 (Affinity Capture-MS), IL2 (Affinity Capture-Western), IL2 (Affinity Capture-MS), IL2 (Affinity Capture-MS), IL2 (Reconstituted Complex), S100A6 (Reconstituted Complex), IL2 (Affinity Capture-MS)

ESM2 similar proteins: A3QPB9, B0ZE70, B3F0J0, C8AW45, O62757, O77762, O97687, P05113, P07750, P10168, P11052, P13232, P15247, P15248, P20096, P20826, P28773, P40221, P40933, P46685, P48092, P48093, P48346, P55030, P60568, P60569, P68290, P68291, P97604, Q1WM29, Q28028, Q29615, Q3S4V6, Q3Y5G8, Q4GZL1, Q4U0U2, Q5WQV8, Q6EAL8, Q6EBC2, Q75SZ9

Diamond homologs: O62641, O77620, O97513, P04351, P05016, P17108, P19114, P26891, P36835, P37997, P46649, P51747, P60568, P60569, P68290, P68291, Q07885, Q08081, Q08867, Q1WM29, Q25BC3, Q29416, Q29615, Q2PE47, Q2PE78, Q4U313, Q5MBA8, Q5PXD0, Q7JFM2, Q7JFM3, Q7JFM4, Q7JFM5, Q865X2, Q865Y1, Q8MKH2, Q95KP3, Q9XS38, Q9XT83, Q9XT84

SIGNOR signaling

8 interactions.

AEffectBMechanism
IL2up-regulatesIL2RAbinding
IL2up-regulatesIL2RBbinding
IL2up-regulatesIL2RGbinding
IL2“up-regulates quantity by expression”NAB2“transcriptional regulation”
IL2“down-regulates quantity by repression”TNFSF10“transcriptional regulation”
CREM“down-regulates quantity by repression”IL2“transcriptional regulation”
NFATC1“up-regulates quantity by expression”IL2“transcriptional regulation”
TBX21“down-regulates quantity by repression”IL2“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic2
Likely pathogenic0
Uncertain significance0
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (2)

Variant IDHGVSClassification
1706620NM_000586.4(IL2):c.433del (p.Cys145fs)Pathogenic
1706621NM_000586.4(IL2):c.134del (p.Ile44_Leu45insTer)Pathogenic

SpliceAI

352 predictions. Top by Δscore:

VariantEffectΔscore
4:122451860:TCCCT:Tacceptor_loss1.0000
4:122451861:CC:Cacceptor_gain1.0000
4:122451862:CC:Cacceptor_gain1.0000
4:122451862:CCTAT:Cacceptor_loss1.0000
4:122451863:CT:Cacceptor_loss1.0000
4:122453704:CCTTA:Cdonor_loss1.0000
4:122453705:CTTA:Cdonor_loss1.0000
4:122453706:TTA:Tdonor_loss1.0000
4:122453707:TAC:Tdonor_loss1.0000
4:122453708:A:ACdonor_gain1.0000
4:122453708:A:Tdonor_loss1.0000
4:122453709:C:CAdonor_loss1.0000
4:122453709:C:CCdonor_gain1.0000
4:122453850:TGGC:Tacceptor_gain1.0000
4:122453851:GGC:Gacceptor_gain1.0000
4:122453852:GC:Gacceptor_gain1.0000
4:122453853:CC:Cacceptor_gain1.0000
4:122453854:C:CCacceptor_gain1.0000
4:122456288:ACTT:Adonor_loss1.0000
4:122456290:TTACA:Tdonor_loss1.0000
4:122456291:TA:Tdonor_loss1.0000
4:122456292:A:ACdonor_gain1.0000
4:122456292:ACA:Adonor_loss1.0000
4:122456293:C:CTdonor_gain1.0000
4:122456293:CA:Cdonor_gain1.0000
4:122456293:CAT:Cdonor_gain1.0000
4:122456293:CATT:Cdonor_gain1.0000
4:122456293:CATTA:Cdonor_gain1.0000
4:122451860:TCC:Tacceptor_gain0.9900
4:122451861:CCC:Cacceptor_gain0.9900

AlphaMissense

1006 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:122451793:A:GW141R0.984
4:122451793:A:TW141R0.984
4:122453813:A:GL83P0.961
4:122451791:C:AW141C0.957
4:122451791:C:GW141C0.957
4:122453834:A:GL76P0.950
4:122453829:A:GC78R0.947
4:122453825:A:GL79P0.938
4:122453714:A:GL116P0.937
4:122453804:A:GL86P0.924
4:122456416:A:GC9R0.919
4:122453828:C:GC78S0.916
4:122453829:A:TC78S0.916
4:122453834:A:TL76H0.916
4:122456319:A:GL41S0.915
4:122456160:A:GF64S0.913
4:122456331:A:GL37S0.913
4:122456402:A:CS13R0.913
4:122456402:A:TS13R0.913
4:122456404:T:GS13R0.913
4:122451801:A:GL138P0.912
4:122453825:A:TL79Q0.908
4:122451782:A:CF144L0.903
4:122451782:A:TF144L0.903
4:122451784:A:GF144L0.903
4:122453827:A:CC78W0.902
4:122451781:A:GC145R0.901
4:122451804:A:GF137S0.901
4:122451779:A:CC145W0.900
4:122453813:A:TL83H0.900

dbSNP variants (sampled 300 via entrez): RS1000418138 (4:122451843 A>G), RS1000871948 (4:122451364 G>C), RS1000947301 (4:122457457 T>G), RS1000957263 (4:122457254 G>A,C), RS1001518101 (4:122456715 T>A), RS10019970 (4:122457436 A>T), RS1002131391 (4:122456844 G>A), RS1002201053 (4:122458235 C>T), RS1002524824 (4:122457222 A>G), RS1003584042 (4:122454894 T>A), RS1003792916 (4:122455228 T>A), RS1004207645 (4:122454926 C>T), RS1004419654 (4:122454077 C>G,T), RS1005317927 (4:122452581 A>T), RS1005660876 (4:122452405 A>T)

Disease associations

OMIM: gene MIM:147680 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast neoplasm (MONDO:0021100)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

55 associations (top):

StudyTraitp-value
GCST000048_2Celiac disease1.000000e-14
GCST000157_8Celiac disease3.000000e-13
GCST000392_21Type 1 diabetes5.000000e-13
GCST000612_34Celiac disease2.000000e-27
GCST000719_2Alopecia areata4.000000e-08
GCST000964_33Ulcerative colitis9.000000e-07
GCST001116_4Progressive supranuclear palsy1.000000e-07
GCST001191_11Type 1 diabetes5.000000e-07
GCST001303_3IgE grass sensitization1.000000e-06
GCST001725_79Inflammatory bowel disease3.000000e-13
GCST002084_6Allergic sensitization6.000000e-10
GCST002318_71Rheumatoid arthritis4.000000e-06
GCST002520_7Celiac disease3.000000e-11
GCST002737_6Atopic dermatitis1.000000e-06
GCST003184_22Atopic dermatitis4.000000e-06
GCST003814_13Selective IgA deficiency1.000000e-06
GCST003990_11Allergy4.000000e-11
GCST004030_4Primary sclerosing cholangitis1.000000e-13
GCST004131_73Inflammatory bowel disease1.000000e-07
GCST004132_89Crohn’s disease9.000000e-07
GCST004644_1Vaso-occlusive pain in sickle-cell anemia6.000000e-08
GCST004866_24Alopecia areata1.000000e-06
GCST004866_28Alopecia areata5.000000e-09
GCST005038_40Allergic disease (asthma, hay fever or eczema)5.000000e-14
GCST005523_20Celiac disease2.000000e-38
GCST005528_12Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)6.000000e-11
GCST005536_11Type 1 diabetes6.000000e-13
GCST005752_140Systemic lupus erythematosus2.000000e-08
GCST006408_9Allergic sensitization1.000000e-08
GCST006409_41Allergic rhinitis3.000000e-15

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0005298allergic sensitization measurement
EFO:0008316vaso-occlusive pain measurement
EFO:0004847age at onset
EFO:1002011adult onset asthma
EFO:0009941Inhalant adrenergic use measurement
EFO:0004842eosinophil count

MeSH disease descriptors (1)

DescriptorNameTree numbers
D001943Breast NeoplasmsC04.588.180; C17.800.090.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5880 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,666 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL242341FORMONONETIN28,420
CHEMBL395414DISOGLUSIDE2246

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs6822844Efficacy3rituximabSystemic lupus erythematosus

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2069762IL20.000
rs2069763IL20.000
rs6822844IL234.751rituximab

Binding affinities (BindingDB)

169 measured of 488 human assays (488 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(2,6-difluorophenyl)thiophene-2-carboxamideIC503 nMUS-8802721: Thiophene compounds for inflammation and immune-related uses
methyl 3-[5-[(2,6-difluorophenyl)carbamoyl]thiophen-2-yl]-4-methylbenzoateIC506.4 nMUS-8802721: Thiophene compounds for inflammation and immune-related uses
US10399967, Compound 98IC508 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 108IC508 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 22IC509 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 73IC509 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 75IC509 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 71IC5010 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 72IC5010 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 109IC5010 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 112IC5010 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 122IC5010 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 70IC5011 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 77IC5011 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 81IC5011 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 99IC5011 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 114IC5011 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 121IC5011 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 7IC5012 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 17IC5012 nMUS-10399967: Compounds for inflammation and immune-related uses
N-(5-(2-chloro-5- cyclopropoxyphenyl)pyrazin-2-yl)-4- methylnicotinamideIC5012 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 14IC5013 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 76IC5013 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 90IC5013 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 144IC5013 nMUS-10399967: Compounds for inflammation and immune-related uses
5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(3-methyl-4-pyridinyl)thiophene-2-carboxamideIC5014 nMUS-8802721: Thiophene compounds for inflammation and immune-related uses
US10399967, Compound 115IC5014 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 116IC5014 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 103IC5016 nMUS-10399967: Compounds for inflammation and immune-related uses
2,6-difluoro-N-[5-[3-(trifluoromethyl)phenyl]thiophen-2-yl]benzamideIC5016.5 nMUS-8802721: Thiophene compounds for inflammation and immune-related uses
US10399967, Compound 137IC5017 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 37IC5018 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 94IC5018 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 104IC5018 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 123IC5018 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 146IC5018 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 24IC5019 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 6IC5020 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 83IC5020 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 131IC5021 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 48IC5022 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 142IC5023 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 8IC5025 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 140IC5025 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 26IC5026 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 27IC5026 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 34IC5026 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 80IC5026 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 9IC5028 nMUS-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 57IC5028 nMUS-10399967: Compounds for inflammation and immune-related uses

ChEMBL bioactivities

116 potent at pChembl≥5 of 124 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.54Kd0.0289nMDISOGLUSIDE
8.59Kd2.59nMCHEMBL3289607
8.52IC503nMCHEMBL3646774
8.19IC506.4nMCHEMBL3646776
8.10IC508nMCHEMBL4857063
8.03EC509.4nMCHEMBL5205694
8.00IC5010nMCHEMBL5087453
7.96IC5011nMCHEMBL4868242
7.94EC5011.56nMCHEMBL5560228
7.89IC5013nMCHEMBL5090091
7.85IC5014nMCHEMBL3646775
7.85IC5014nMCHEMBL4869725
7.78IC5016.5nMCHEMBL3646778
7.70Kd20nMGALUTEOLIN
7.60EC5025.3nMCHEMBL5398436
7.50IC5032nMCHEMBL4868367
7.47IC5034nMCHEMBL4848840
7.47IC5034nMCHEMBL4861512
7.47IC5034nMCHEMBL5088468
7.45Kd35.6nMCHEMBL3289608
7.45EC5035.2nMCHEMBL5404419
7.41IC5039nMCHEMBL5084598
7.34EC5045.37nMCHEMBL5557745
7.33IC5047nMCHEMBL5074957
7.30IC5050nMCHEMBL4868517
7.26Kd54.9nMCHEMBL3289611
7.26IC5055nMCHEMBL4859192
7.23IC5058.5nMCHEMBL3646777
7.22IC5060nMCHEMBL429852
7.22Ki60nMCHEMBL429852
7.19IC5064nMCHEMBL4859714
7.19IC5064.8nMCHEMBL4855379
7.16IC5069nMCHEMBL4854994
7.14EC5072.91nMCHEMBL5523660
7.11IC5078nMCHEMBL4872086
7.10IC5080nMCHEMBL4857666
7.09IC5082nMCHEMBL5079033
7.06IC5087nMCHEMBL3646781
7.04IC5091nMCHEMBL5082562
7.04EC5090.4nMCHEMBL5558965
7.03IC5094.4nMCHEMBL4868543
7.02IC5094.8nMCHEMBL3646780
7.02IC5096nMCHEMBL5086824
7.01EC5097.27nMCHEMBL5557243
7.00Kd100nMCHEMBL429852
6.99IC50103.6nMCHEMBL3646779
6.96EC50108.4nMCHEMBL5561221
6.95IC50113nMCHEMBL5080834
6.92Kd120nMONONIN
6.82IC50150nMCHEMBL4848699

PubChem BioAssay actives

84 with measured affinity, of 160 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[(1S,2S,4S,5’R,6R,7S,8R,9S,12S,13R,16S)-5’,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-18-ene-6,2’-oxane]-16-yl]oxyoxane-3,4,5-triol1156797: Binding affinity to IL-2 (unknown origin)kd<0.0001uM
methyl (4S,5Z,6S)-5-ethylidene-4-[2-oxo-2-[[(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)ethoxy]oxan-2-yl]methoxy]ethyl]-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4H-pyran-3-carboxylate1156797: Binding affinity to IL-2 (unknown origin)kd0.0026uM
N-[4-[2-chloro-5-(trifluoromethyl)phenyl]phenyl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0080uM
(3S)-6-[[5-[(1R)-1-amino-1-cyclopropylethyl]-8-cyclopropyloxy-2,7-naphthyridin-3-yl]amino]-3-methylspiro[2,3-dihydronaphthalene-4,1’-cyclopropane]-1-one1884769: Inhibition of IL-2 (unknown origin)ec500.0094uM
(2S)-N-[2-[(4aS,5aR)-5,5-difluoro-5a-methyl-1,4,4a,6-tetrahydrocyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0100uM
2,6-difluoro-N-[4-[2-methyl-3-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]phenyl]benzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0110uM
3-(3,4-dimethoxyphenyl)-5-[4-(1-methylpiperidin-4-yl)phenyl]-1H-pyrrolo[2,3-b]pyridine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.0116uM
(2R)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-3H-benzimidazol-5-yl]-N-methyl-2-(oxan-4-yl)propanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0130uM
2-chloro-6-fluoro-N-[4-[2-methyl-3-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]phenyl]benzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0140uM
2-(3,4-dihydroxyphenyl)-5-hydroxy-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one1156797: Binding affinity to IL-2 (unknown origin)kd0.0200uM
N-[1-[(1S)-3-[[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]amino]-6-oxohexyl]-methylamino]-1-phenylpropyl]pyrazol-4-yl]-6,6-dimethyl-1,4,5,7-tetrahydroindazole-3-carboxamide;2,2,2-trifluoroacetic acid2029692: Inhibition of IL-2 in human Jurkat cells pretreated with compound for 4 hrs followed by anti-CD3/CD28 stimulation by ELISA analysisec500.0253uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-ethylphenyl]pyrazin-2-yl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0320uM
N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-3H-benzimidazol-5-yl]-2,2-difluoro-N-methyl-2-(oxan-4-yl)acetamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0340uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0340uM
2,6-difluoro-N-[4-[2-methyl-5-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]phenyl]benzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0340uM
N-[1-[(1S)-3-[4-[2-[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidin-4-yl]ethyl]piperazin-1-yl]-1-phenylpropyl]pyrazol-4-yl]-6,6-dimethyl-1,4,5,7-tetrahydroindazole-3-carboxamide;2,2,2-trifluoroacetic acid2029692: Inhibition of IL-2 in human Jurkat cells pretreated with compound for 4 hrs followed by anti-CD3/CD28 stimulation by ELISA analysisec500.0352uM
3-(3-hydroxy-4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one1156797: Binding affinity to IL-2 (unknown origin)kd0.0356uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0390uM
3-(3,4-dimethoxyphenyl)-5-[4-(oxan-4-yl)phenyl]-1H-pyrrolo[2,3-b]pyridine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.0454uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-7-fluoro-6-methyl-3H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0470uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methoxyphenyl]pyrazin-2-yl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0500uM
2-cyclohexyl-2-(diaminomethylideneamino)-N-[2-[4-[3-(2,3-dichlorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl]-2-oxoethyl]acetamide1156797: Binding affinity to IL-2 (unknown origin)kd0.0549uM
N-[5-[3-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0550uM
5-[[2,3-dichloro-4-[5-[1-[2-[[(2R)-2-(diaminomethylideneamino)-4-methylpentanoyl]amino]acetyl]piperidin-4-yl]-1-methylpyrazol-3-yl]phenoxy]methyl]furan-2-carboxylic acid318564: Binding affinity to IL2 assessed as inhibition of IL2-IL2Ralpha interactionki0.0600uM
2,6-difluoro-N-[5-[2-methyl-5-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]pyrazin-2-yl]benzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0640uM
2-chloro-N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-6-fluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0648uM
N-[4-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]phenyl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0690uM
3-(3,4-dimethoxyphenyl)-5-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-1H-pyrrolo[2,3-b]pyridine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.0729uM
N-[4-[5-(4-ethyl-5-oxo-1,3,4-oxadiazol-2-yl)-2-methylphenyl]phenyl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0780uM
N-(4-benzoylphenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide1763550: Inhibition of IL2-induced STAT3 phosphorylation in human NK92 cells incubated for 30 mins followed by IL-15 stimulation and measured after 1 hr by alphascreen assayic500.0800uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-7-hydroxy-3H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0820uM
3-(3,4-dimethoxyphenyl)-5-(4-piperazin-1-ylphenyl)-1H-pyrrolo[2,3-b]pyridine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.0904uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-ethyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0910uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-3,5-difluoropyridine-4-carboxamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.0944uM
N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-(3-oxomorpholin-4-yl)acetamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.0960uM
4-[4-[3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]morpholine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.0973uM
3-(3,4-dimethoxyphenyl)-5-(6-piperazin-1-yl-3-pyridinyl)-1H-pyrrolo[2,3-b]pyridine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.1084uM
(2R)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assayic500.1130uM
3-(4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one1156797: Binding affinity to IL-2 (unknown origin)kd0.1200uM
N-(2,6-difluorophenyl)-5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazine-2-carboxamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.1500uM
2-chloro-N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]benzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.1710uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]-2-pyridinyl]-2,6-difluorobenzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.1780uM
(2R)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]-3-(4-hydroxy-3-iodophenyl)propanoic acid1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assaykd0.2100uM
2,6-difluoro-N-[4-[2-methyl-5-(2-oxo-3H-1,3,4-oxadiazol-5-yl)phenyl]phenyl]benzamide1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISAic500.2270uM
N-[5-[5-(4-acetylpiperazine-1-carbonyl)-4-methoxy-2-methylphenyl]sulfanyl-1,3-thiazol-2-yl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide2029693: Inhibition of IL-2 in human Jurkat T cells pretreated with compound for 16 hrs followed by anti-CD3 stimulation by ELISA analysisec500.2376uM
(2S)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]-3-(3-iodophenyl)propanoic acid1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assaykd0.2500uM
(2S)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]-3-(4-hydroxy-3-iodophenyl)propanoic acid1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assaykd0.2500uM
3-(3,4-dimethoxyphenyl)-5-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1H-pyrrolo[2,3-b]pyridine2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISAec500.2750uM
(2S)-2-[(6-fluoro-1H-indole-2-carbonyl)amino]-3-(4-hydroxy-3-iodophenyl)propanoic acid1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assaykd0.2800uM
(2S)-3-(3-bromo-4-hydroxyphenyl)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]propanoic acid1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assaykd0.3000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Tetradecanoylphorbol Acetateincreases reaction, affects reaction, increases expression, increases activity, decreases reaction (+4 more)31
Ionomycindecreases expression, affects reaction, increases activity, affects cotreatment, increases secretion (+3 more)20
Lipopolysaccharidesaffects cotreatment, increases expression, increases secretion, increases reaction, decreases reaction (+1 more)8
Dexamethasoneincreases reaction, decreases response to substance, affects reaction, affects cotreatment, decreases reaction (+4 more)7
Tacrolimusaffects cotreatment, decreases expression, decreases reaction, increases expression7
Particulate Matterincreases expression, decreases expression6
Arsenicaffects cotreatment, increases expression, decreases expression, decreases secretion, increases abundance5
Vehicle Emissionsaffects cotreatment, decreases expression, increases expression5
Plant Extractsincreases secretion, affects reaction, decreases reaction, affects expression, decreases expression (+2 more)5
Zincaffects expression, affects cotreatment, affects reaction, increases expression, decreases expression5
sodium arseniteincreases expression, decreases reaction, increases secretion, decreases expression, decreases secretion (+2 more)4
Ribavirinaffects cotreatment, increases reaction, increases secretion, increases expression4
Tretinoindecreases activity, increases reaction, increases secretion, decreases expression, increases expression4
Calcitrioldecreases reaction, increases phosphorylation, decreases expression, decreases secretion3
Methotrexateaffects reaction, decreases secretion, affects cotreatment, increases expression3
Cyclosporineaffects cotreatment, decreases expression, decreases reaction, increases expression3
Sirolimusaffects cotreatment, decreases reaction, increases expression, increases phosphorylation, decreases response to substance3
cobaltous chlorideaffects cotreatment, decreases expression, decreases secretion2
nickel chlorideaffects cotreatment, increases secretion, decreases reaction, increases activity2
cordycepindecreases secretion2
SB 203580increases secretion, affects reaction, increases expression, affects cotreatment, decreases reaction2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-onedecreases reaction, increases expression, increases activity, increases phosphorylation, affects cotreatment (+1 more)2
Calcimycinaffects cotreatment, decreases reaction, increases expression, increases secretion2
Resveratrolaffects cotreatment, decreases reaction, increases expression, decreases expression2
Zoledronic Acidincreases reaction, affects expression, affects reaction2
Alitretinoinincreases reaction, increases secretion, decreases expression2
Acetylcysteinedecreases reaction, increases phosphorylation, decreases activity, decreases abundance, decreases expression2
Chloroquineaffects cotreatment, decreases expression2
Chlorpromazineincreases phosphorylation, affects cotreatment, decreases expression, decreases reaction2
Coaldecreases expression, increases abundance2

ChEMBL screening assays

35 unique, capped per target: 34 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3077408BindingBinding affinity to IL2 (unknown origin) assessed as inhibition of binding to IL2 receptor alphaIn vitro and in silico exploration of IL-2 inhibition by small drug-like molecules — Med Chem Res
CHEMBL5029737ADMETInduction of stability of human recombinant interleukin 2 assessed as area under curve in Sprague-Dawley rat at 0.8 mg/kg, iv measured up to 24 hrs by ELISA (Rvb= 251.22 +/- 11.60 ng.hr/ml)Enhancing the Pharmacokinetic Profile of Interleukin 2 through Site-Specific Conjugation to a Selective Small-Molecule Transthyretin Ligand. — J Med Chem

Cellosaurus cell lines

23 cell lines: 23 cancer cell line

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

CellosaurusNameCategorySex
CVCL_3755NK-92MICancer cell lineMale
CVCL_6923JEG-3/VP16-IL-2Cancer cell lineMale
CVCL_A9JCP815 Hsp65-IL-2Cancer cell lineMale
CVCL_B3PCTR-IL2-NK-92Cancer cell lineMale
CVCL_B3PDTR-IL2-YTCancer cell lineMale
CVCL_C3HMRCC-26/CD80/IL-2Cancer cell line
CVCL_E3G7RenCa/IL2HiCancer cell lineMale
CVCL_E3G8RenCa/IL2MoCancer cell lineMale
CVCL_E4CQNCI-H69/IL2Cancer cell lineMale
CVCL_E4CRNCI-H69/IL2/IFN-gammaCancer cell lineMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00092183PHASE4COMPLETEDAn Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071)
NCT00128778PHASE4COMPLETEDMaintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients
NCT00302120PHASE4UNKNOWNThe MONET - Study: MR Mammography of Nonpalpable Breast Tumors
NCT00307606PHASE4UNKNOWNDoes a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma
NCT00370240PHASE4COMPLETEDChlorhydrate of Ropivacaine and Breast Cancer Surgery
NCT00375752PHASE4TERMINATEDEfficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
NCT00575354PHASE4COMPLETEDComparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision
NCT00604968PHASE4TERMINATEDPegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
NCT00616135PHASE4COMPLETEDStudy of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy
NCT00649090PHASE4COMPLETEDA Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer
NCT00779285PHASE4TERMINATEDSafety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED)
NCT01176916PHASE4COMPLETEDAromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China
NCT01427400PHASE4UNKNOWNThe Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01849380PHASE4UNKNOWNNeoadjuvant ECS Versus ECF in Local Advanced Breast Cancer
NCT01859936PHASE4COMPLETEDWill Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment
NCT01948960PHASE4COMPLETEDInfluence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01961544PHASE4COMPLETEDEribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer
NCT01975064PHASE4COMPLETEDCancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT02004834PHASE4ACTIVE_NOT_RECRUITINGLevobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02372305PHASE4WITHDRAWNComparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery
NCT02479347PHASE4COMPLETEDWound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine
NCT02549677PHASE4COMPLETEDEpirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer
NCT02612870PHASE4UNKNOWNSienna+® Injection Time Study 4 Arms
NCT02627560PHASE4COMPLETEDThe Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy
NCT02661932PHASE4COMPLETEDFertility Preservation in Breast Cancer Patients
NCT02781259PHASE4UNKNOWNSelective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer
NCT02819921PHASE4TERMINATEDDesvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen
NCT03220178PHASE4TERMINATEDImpact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03583944PHASE4COMPLETEDA Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer
NCT03586154PHASE4COMPLETEDCombined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
NCT04707196PHASE4COMPLETEDA Study of Abemaciclib in Indian Women With Advanced Breast Cancer
NCT04931615PHASE4COMPLETEDARTISS a Single-centre Randomised Control Study
NCT05033769PHASE4UNKNOWNAssessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
NCT05036005PHASE4UNKNOWNNeoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT05452213PHASE4RECRUITINGComprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT05465031PHASE4RECRUITINGSacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
NCT05949333PHASE4UNKNOWNReducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy
NCT07158164PHASE4RECRUITINGDPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07162259PHASE4NOT_YET_RECRUITINGCohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
NCT00000611PHASE3COMPLETEDWomen’s Health Initiative (WHI)