IL15RA

Summary

IL15RA (interleukin 15 receptor subunit alpha, HGNC:5978) is a protein-coding gene on chromosome 10p15.1, encoding Interleukin-15 receptor subunit alpha (Q13261). High-affinity receptor for interleukin-15.

This gene encodes a cytokine receptor that specifically binds interleukin 15 (IL15) with high affinity. The receptors of IL15 and IL2 share two subunits, IL2R beta and IL2R gamma. This forms the basis of many overlapping biological activities of IL15 and IL2. The protein encoded by this gene is structurally related to IL2R alpha, an additional IL2-specific alpha subunit necessary for high affinity IL2 binding. Unlike IL2RA, IL15RA is capable of binding IL15 with high affinity independent of other subunits, which suggests distinct roles between IL15 and IL2. This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported.

Source: NCBI Gene 3601 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• MANE Select transcript: NM_002189

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5978
Approved symbol	IL15RA
Name	interleukin 15 receptor subunit alpha
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Aliases	CD215, IL-15RA
Ensembl gene	ENSG00000134470
Ensembl biotype	protein_coding
OMIM	601070
Entrez	3601

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 28 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000379971, ENST00000379972, ENST00000379974, ENST00000379977, ENST00000397246, ENST00000397248, ENST00000397250, ENST00000397251, ENST00000397255, ENST00000429135, ENST00000435171, ENST00000447291, ENST00000453922, ENST00000525219, ENST00000528354, ENST00000530685, ENST00000532039, ENST00000532948, ENST00000534292, ENST00000620345, ENST00000620865, ENST00000622442, ENST00000851419, ENST00000851421, ENST00000851422, ENST00000851424, ENST00000851425, ENST00000851427, ENST00000851428, ENST00000962787, ENST00000962788, ENST00000962789

RefSeq mRNA: 7 — MANE Select: NM_002189 NM_001243539, NM_001256765, NM_001351095, NM_001351096, NM_001351097, NM_002189, NM_172200

CCDS: CCDS58069, CCDS7074, CCDS7075, CCDS73065

Canonical transcript exons

ENST00000379977 — 7 exons

Exon	Start	End
ENSE00001000818	5952384	5953206
ENSE00001951830	5977405	5977543
ENSE00003493013	5956379	5956454
ENSE00003509900	5963743	5963841
ENSE00003526701	5966145	5966339
ENSE00003529556	5960367	5960567
ENSE00003787645	5959754	5959786

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 95.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8929 / max 303.1908, expressed in 1404 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108124	4.7584	998
108123	4.4358	945
108125	1.8797	703
108126	0.5371	323
108122	0.1490	64
108127	0.1329	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	95.06	gold quality
upper lobe of left lung	UBERON:0008952	94.17	gold quality
upper lobe of lung	UBERON:0008948	92.97	gold quality
endocervix	UBERON:0000458	92.30	gold quality
gall bladder	UBERON:0002110	91.81	gold quality
ectocervix	UBERON:0012249	91.79	gold quality
mucosa of stomach	UBERON:0001199	91.49	gold quality
left uterine tube	UBERON:0001303	91.05	gold quality
apex of heart	UBERON:0002098	90.64	gold quality
body of uterus	UBERON:0009853	90.21	gold quality
omental fat pad	UBERON:0010414	90.03	gold quality
peritoneum	UBERON:0002358	89.94	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.25	gold quality
right atrium auricular region	UBERON:0006631	88.96	gold quality
right coronary artery	UBERON:0001625	88.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.15	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.47	gold quality
body of stomach	UBERON:0001161	87.15	gold quality
left coronary artery	UBERON:0001626	87.00	gold quality
right lobe of liver	UBERON:0001114	86.96	gold quality
monocyte	CL:0000576	86.95	gold quality
granulocyte	CL:0000094	86.94	gold quality
cardiac atrium	UBERON:0002081	86.86	gold quality
right lobe of thyroid gland	UBERON:0001119	86.56	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.54	gold quality
mononuclear cell	CL:0000842	86.45	gold quality
leukocyte	CL:0000738	86.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.23	gold quality
lower esophagus	UBERON:0013473	86.17	gold quality
body of pancreas	UBERON:0001150	86.11	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting IL15RA, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6727-5P	92.41	61.98	83
HSA-MIR-3912-3P	88.31	65.41	84

Literature-anchored findings (GeneRIF, showing 40)

• mRNA for IL-15 receptor alpha was constitutively expressed in all tested human fetal brain structures, indicating a role in their development and physiology (PMID:12114302)
• il15 induce anti-tumor immune response (PMID:12115611)
• interleukin-15alpha receptor binds to IL-15 at specific binding sites, one in the B helix and the other in the C helix (PMID:15039446)
• IL-2R alpha, IL-15R alpha, IL-2/15R beta and gamma(c)-subunits, as well as MHC class I and II glycoproteins formed supramolecular receptor clusters in lipid rafts of the T lymphoma line. (PMID:15263076)
• Soluble IL-15R alpha arises from proteolytic shedding of the membrane-anchored receptor. It is an inhibitor of IL-15 binding to the membrane receptor & of IL-15-induced cell proliferation. IL-15R alpha shedding may have major immunoregulatory functions. (PMID:15265897)
• IL-15 is an important mediator of muscle mass response to resistance exercise training in humans and that genetic variation in IL15RA accounts for a significant proportion of the variability in this response. (PMID:15531573)
• A quantitative relationship is established between receptor alpha subunit binding affinity and mitogenic activity for IL-15 and IL-2. (PMID:16060678)
• IL-15R alpha, which bears most of the binding affinity for IL-15, behaves as a potent IL-15 agonist by enhancing its binding and biological effects through the IL-15R beta/gamma heterodimer. (PMID:16284400)
• Study of three-dimensional structure of IL-15 receptor (IL-15R) alpha chain has led to a model of the IL-15.IL-15R alpha complex that reveals involvement of a large network of ionic interactions not observed in other cytokine/cytokine receptor complexes. (PMID:16377614)
• Results show that the biological activity of soluble IL-15 is much improved after interaction with recombinant soluble IL-15Ralpha. (PMID:16757567)
• results confirm that signal transduction via the IL-15R, and hence NK ontogeny, is preferentially retained relative to the IL-7R as gammac expression becomes limiting. (PMID:17363735)
• IL-15 and IL-15Ralpha complex is 10-fold more active than IL-15 alone in stimulating proliferation and survival of memory phenotype CD8 T cells. (PMID:17655329)
• Data show that NK cell survival mediated through the regulatory synapse with human dendritic cells requires IL-15Ralpha. (PMID:17948125)
• We here confirm clustering of IL2Ralpha and IL15Ralpha at the submicron scale. Our single-molecule data reveal that a non-negligible percentage of the receptors are organized as monomers. (PMID:18287585)
• sIL-15Ralpha has a protumor role in cancer (PMID:18483276)
• Interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs independently of the presence of IL-15 receptor alpha (IL-15R alpha). (PMID:18505820)
• Potential involvement with muscle and bone phenotypes and predictors of metabolic syndrome. (PMID:18514540)
• The soluble IL-15Ralpha sushi domain-IL-15 fusion protein is therefore able to bind and activate both the IL-15Rbeta/gamma and the IL-15Ralpha/beta/gamma receptors. (PMID:18656487)
• genetic variability of the IL-15 receptor has an important role in body fat composition. (PMID:19309557)
• These analyses unveiled a novel and critical role for residue Tyr26 of IL-15 in the interaction with IL-15R alpha, which facilitates desolvation of key charged residues during the assembly of the complex. (PMID:19406127)
• IL-15 receptor alpha facilitates the stability and secretion of the IL-15 short signal peptide, a soluble and bioactive isoform. (PMID:19696432)
• IFN-gamma and TNF-alpha play an important role in regulating the expression of IL-15 and IL-15Ralpha on the surface of HUVECs. (PMID:19821081)
• IL-2, IL15 and IL-15Ralpha-IgG1-Fc complexes significantly enhanced NK and CD8(+) T cells proliferation and cytotoxicity. (PMID:20671116)
• broad expression pattern of functional IL-15RA splicing forms and suggests a regulatory role of DNA methylation in IL-15RA transcript Var1 expression in mononuclear cells (PMID:21097393)
• The expression of IL-15Ralpha on CD8 T cells is required for uncontrolled aggressive lymphoproliferation; none of the IL-15Ralpha(-/-)-IL-15 mice that we followed for more than 2 years developed the fatal disease despite controlled expansion of CD8 T cells (PMID:21304101)
• These results suggest that IL15RA polymorphism may be associated with the susceptibility of ossification of the posterior longitudinal ligament in Korean population. (PMID:21689944)
• Different levels of IL-15 trans-presentation are required for different natural killer (NK) cell developmental events to reach full maturation status (PMID:21715685)
• IFN-alpha boosts signaling and functional effects of IL-15, at least in part by fostering the increased IL-15R expression (PMID:21813181)
• High serum IL-15R alpha is associated with T-cell large granular lymphocyte leukemia. (PMID:22049515)
• IL-15 can signal via IL-15Ralpha, JNK, and NF-kappaB to drive RANTES production by myeloid cells. (PMID:22447977)
• IL-15 is produced and secreted only as a heterodimer with IL-15Ralpha. (PMID:22496150)
• Human Langerhans cells use an IL-15R-alpha/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1. (PMID:22510877)
• Letter: report increased frequency of CD127/CD215 co-expressing CD4(+) T cells in Wegener’s granulomatosis. (PMID:22640659)
• The inflammatory bowel diseases patients have an increased expression of IL-15Ralpha mRNA in the mucosa; expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. (PMID:23039249)
• regulator of the oxidative and fatigue properties of skeletal muscle [review] (PMID:23072822)
• Paracrine and transpresentation functions of IL-15 are mediated by diverse splice form of IL-15Ralpha. (PMID:23074221)
• The proportion of IL-15Ralpha expression on total leukocytes was much lower for all rheumatic diseases, including Behcet disease, than in healthy controls (PMID:23417200)
• lower frequencies of IL-15RA-positive T cells in Behcet’s disease (PMID:23618691)
• Data show efficient production of noncovalently linked but stable heterodimer in clonal HEK293 cells and release of the processed IL-15.sIL-15Ralpha heterodimer in the medium. (PMID:23649624)
• Data indicate that tumor necrosis factor-alpha (TNF) abolishes nuclear localization of IL-15 and IL-15Ralpha by acting on chromosomal region maintenance 1 (CRM1), and it facilitates exocytosis of IL-15 with the involvement of ADP-ribosylation factor 6 (ARF6). (PMID:23950892)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	il15ra	ENSDARG00000069311
mus_musculus	Il15ra	ENSMUSG00000023206
rattus_norvegicus	Il15ra	ENSRNOG00000018706

Protein

Protein identifiers

Interleukin-15 receptor subunit alpha — Q13261 (reviewed: Q13261)

All UniProt accessions (12): Q13261, A0A0A0MS77, E7ETI1, E9PQ64, H0Y4R3, H0Y6E8, H0YD11, K9N163, K9N1J3, K9N2Q6, K9N2S2, Q5JVA3

UniProt curated annotations — full annotation on UniProt →

Function. High-affinity receptor for interleukin-15. Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells. In neutrophils, binds and activates kinase SYK in response to IL15 stimulation. In neutrophils, required for IL15-induced phagocytosis in a SYK-dependent manner. Expression of different isoforms may alter or interfere with signal transduction. Does not bind IL15. Does not bind IL15. Does not bind IL15. Does not bind IL15.

Subunit / interactions. The interleukin-15 receptor IL15R is a heterotrimer of IL15RA, IL2RB and IL2RG. IL15RA also self-associates. Interacts with SYK.

Subcellular location. Membrane. Nucleus membrane. Cell surface Endoplasmic reticulum membrane. Golgi apparatus membrane. Cytoplasmic vesicle membrane. Membrane Endoplasmic reticulum membrane. Membrane Secreted. Extracellular space.

Tissue specificity. Expressed in neutrophils (at protein level). Expressed in fetal brain with higher expression in the hippocampus and cerebellum than in cortex and thalamus. Higher levels of soluble sIL-15RA form in comparison with membrane-bound forms is present in all brain structures. Isoforms 1, 3, 4, 5, 6, 7, 8 and 9: Widely expressed.

Post-translational modifications. N-glycosylated and O-glycosylated. A soluble form (sIL-15RA) arises from proteolytic shedding of the membrane-anchored receptor. It also binds IL-15 and thus interferes with IL-15 binding to the membrane receptor.

Isoforms (9)

UniProt ID	Names	Canonical?
Q13261-1	1	yes
Q13261-3	2, delta3E1E7Il-15RA
Q13261-4	3, E1E7’Il-15RA
Q13261-5	4, delta3E1E7’Il-15RA
Q13261-6	5, delta2E1E7Il-15RA
Q13261-7	6, delta2E1E7’Il-15RA
Q13261-8	7, delta2deltaE1E73Il-15RA
Q13261-9	8, delta2delta3E1E7’Il-15RA
Q13261-10	9

RefSeq proteins (7): NP_001230468, NP_001243694, NP_001338024, NP_001338025, NP_001338026, NP_002180, NP_751950 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR042372	IL15RA	Family

UniProt features (29 total): strand 6, splice variant 5, compositionally biased region 3, chain 2, disulfide bond 2, topological domain 2, signal peptide 1, glycosylation site 1, sequence variant 1, sequence conflict 1, turn 1, helix 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2Z3Q	X-RAY DIFFRACTION	1.85
2Z3R	X-RAY DIFFRACTION	2
4GS7	X-RAY DIFFRACTION	2.35
2ERS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13261-F1	65.41	0.27

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 (2): 33–75, 59–93

Glycosylation sites (1): 137

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8983432	Interleukin-15 signaling

MSigDB gene sets: 380 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, MODULE_169, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOLDRATH_IMMUNE_MEMORY, MODULE_522, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (7): natural killer cell differentiation (GO:0001779), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), negative regulation of neuron projection development (GO:0010977), response to nutrient levels (GO:0031667), positive regulation of natural killer cell differentiation (GO:0032825), interleukin-15-mediated signaling pathway (GO:0035723), positive regulation of phagocytosis (GO:0050766)

GO Molecular Function (4): cytokine receptor activity (GO:0004896), protein kinase binding (GO:0019901), interleukin-15 receptor activity (GO:0042010), protein binding (GO:0005515)

GO Cellular Component (14): Golgi membrane (GO:0000139), extracellular region (GO:0005576), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), cytoplasmic vesicle membrane (GO:0030659), nuclear membrane (GO:0031965), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-2 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	4
endomembrane system	3
intracellular membrane-bounded organelle	3
cytokine-mediated signaling pathway	2
cytoplasmic vesicle	2
organelle membrane	2
lymphocyte differentiation	1
natural killer cell activation	1
cell surface receptor signaling pathway via STAT	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
response to stimulus	1
natural killer cell differentiation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell differentiation	1
positive regulation of lymphocyte differentiation	1
cellular response to interleukin-15	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
transmembrane signaling receptor activity	1
cytokine binding	1
immune receptor activity	1
kinase binding	1
cytokine receptor activity	1
interleukin-15-mediated signaling pathway	1
interleukin-15 binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
vesicle membrane	1
nucleus	1
nuclear envelope	1
intracellular vesicle	1

Protein interactions and networks

STRING

1342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL15RA	IL15	P40933	999
IL15RA	IL2RG	P31785	997
IL15RA	IL2	P01585	992
IL15RA	IL2RB	P14784	990
IL15RA	IL2RA	P01589	946
IL15RA	IL7	P13232	851
IL15RA	IL7R	P16871	842
IL15RA	KLRK1	P26718	806
IL15RA	CD8A	P01732	780
IL15RA	IL9	P15248	768
IL15RA	IL21R	Q9HBE5	665
IL15RA	TNF	P01375	657
IL15RA	IL6	P05231	647
IL15RA	CD69	Q07108	642
IL15RA	IL12RB1	P42701	633

IntAct

13 interactions, top by confidence:

A	B	Type	Score
IL2RB	IL15	psi-mi:“MI:0915”(physical association)	0.660
IL15	IL15RA	psi-mi:“MI:0915”(physical association)	0.660
IL15RA	IL15	psi-mi:“MI:0915”(physical association)	0.660
IL15RA	IL2RB	psi-mi:“MI:0915”(physical association)	0.590
CDK2	IL15RA	psi-mi:“MI:0915”(physical association)	0.370
IL15RA	CDK4	psi-mi:“MI:0915”(physical association)	0.370
IL15RA	RCVRN	psi-mi:“MI:0915”(physical association)	0.370
IL15RA	CASK	psi-mi:“MI:0915”(physical association)	0.370
IL15RA	BCL10	psi-mi:“MI:0915”(physical association)	0.370
PIAS4	IL15RA	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (8): IL15RA (Affinity Capture-MS), IL15RA (Affinity Capture-Western), IL15RA (Two-hybrid), IL15RA (Two-hybrid), RCVRN (Two-hybrid), PIAS4 (Two-hybrid), IL15RA (Two-hybrid), IL15RA (Two-hybrid)

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2APT9, B0BN44, B1ARY8, B6ZI38, O14836, O35188, O55145, O60279, O60667, P07141, P09603, P0C8S2, P28906, P40225, P40226, P42705, P78423, Q06154, Q08DV9, Q13261, Q1ERP8, Q28270, Q2TB54, Q3UY90, Q4V9H3, Q4W8E7, Q5F267, Q5R770, Q60819, Q64314, Q6PAL1, Q6PCP7, Q6UXB8, Q80XI1, Q8BLK9, Q8CAE9, Q8CBC4, Q8JZQ0

Diamond homologs: Q13261, Q60819

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
IL15	up-regulates	IL15RA	binding
IL15RA	up-regulates	IL2RB	binding
SYK	“up-regulates activity”	IL15RA	phosphorylation
IL15RA	up-regulates	JAK3	phosphorylation
IL15RA	up-regulates	JAK3
IL15RA	“down-regulates activity”	PPARG
IL15RA	up-regulates	TIMP3
IL15RA	up-regulates	TYK2
IL15RA	up-regulates	JAK1

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1353 predictions. Top by Δscore:

Variant	Effect	Δscore
10:5956455:C:CC	acceptor_gain	1.0000
10:5966143:A:AC	donor_gain	1.0000
10:5966144:C:CC	donor_gain	1.0000
10:5977404:CCCCG:C	donor_gain	1.0000
10:5953812:C:CA	donor_gain	0.9900
10:5953852:CGTGG:C	donor_gain	0.9900
10:5956451:GCCA:G	acceptor_gain	0.9900
10:5956452:CCA:C	acceptor_gain	0.9900
10:5956452:CCAC:C	acceptor_gain	0.9900
10:5956453:CA:C	acceptor_gain	0.9900
10:5956453:CAC:C	acceptor_gain	0.9900
10:5956640:T:A	donor_gain	0.9900
10:5959748:ACTT:A	donor_loss	0.9900
10:5959749:CTTA:C	donor_loss	0.9900
10:5959751:T:TG	donor_loss	0.9900
10:5966144:CT:C	donor_gain	0.9900
10:5966144:CTA:C	donor_gain	0.9900
10:5966144:CTAA:C	donor_gain	0.9900
10:5966144:CTAAT:C	donor_gain	0.9900
10:5977399:CCCTA:C	donor_loss	0.9900
10:5977400:CCTAC:C	donor_loss	0.9900
10:5977401:CTACC:C	donor_loss	0.9900
10:5977402:TA:T	donor_loss	0.9900
10:5977403:AC:A	donor_gain	0.9900
10:5977403:ACC:A	donor_gain	0.9900
10:5977403:ACCCC:A	donor_loss	0.9900
10:5977404:C:A	donor_loss	0.9900
10:5977404:CC:C	donor_gain	0.9900
10:5977404:CCC:C	donor_gain	0.9900
10:5958278:AT:A	donor_gain	0.9800

AlphaMissense

1695 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:5966170:C:A	W86C	1.000
10:5966170:C:G	W86C	1.000
10:5966150:C:G	C93S	0.999
10:5966151:A:T	C93S	0.999
10:5966252:C:G	C59S	0.999
10:5966253:A:T	C59S	0.999
10:5966172:A:G	W86R	0.998
10:5966172:A:T	W86R	0.998
10:5966204:C:G	C75S	0.998
10:5966205:A:T	C75S	0.998
10:5966235:G:T	R65S	0.998
10:5966239:G:C	F63L	0.998
10:5966239:G:T	F63L	0.998
10:5966241:A:G	F63L	0.998
10:5966252:C:T	C59Y	0.998
10:5966151:A:G	C93R	0.997
10:5966205:A:G	C75R	0.997
10:5966251:A:C	C59W	0.997
10:5966253:A:G	C59R	0.997
10:5966236:C:A	K64N	0.996
10:5966236:C:G	K64N	0.996
10:5966252:C:A	C59F	0.996
10:5966149:G:C	C93W	0.994
10:5966171:C:G	W86S	0.994
10:5966203:G:C	C75W	0.994
10:5966258:T:C	Y57C	0.994
10:5966240:A:G	F63S	0.993
10:5966331:A:G	C33R	0.993
10:5966240:A:C	F63C	0.992
10:5966259:A:C	Y57D	0.992

dbSNP variants (sampled 300 via entrez): RS1000010444 (10:5964224 T>C), RS1000018148 (10:5958290 T>C), RS1000085300 (10:5963908 G>A,C), RS1000270987 (10:5969484 C>G,T), RS1000369290 (10:5958535 G>A), RS1000373609 (10:5975657 C>A,T), RS1000448871 (10:5975468 A>C), RS1000546143 (10:5977389 G>A), RS1000644135 (10:5969731 C>A,G), RS1000815304 (10:5954020 G>A,C), RS1000853898 (10:5965430 G>A,T), RS1000864419 (10:5953744 C>A), RS1000905018 (10:5953620 C>T), RS1001012965 (10:5959825 A>C), RS1001086687 (10:5965343 C>G)

Disease associations

OMIM: gene MIM:601070 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001725_103	Inflammatory bowel disease	4.000000e-10
GCST001911_1	Asthma (bronchodilator response)	2.000000e-07
GCST002875_32	Diisocyanate-induced asthma	2.000000e-06
GCST003088_1	Soluble interleukin-2 receptor subunit alpha	1.000000e-100
GCST003088_5	Soluble interleukin-2 receptor subunit alpha	2.000000e-10
GCST003184_15	Atopic dermatitis	2.000000e-06
GCST003184_7	Atopic dermatitis	1.000000e-10
GCST004866_17	Alopecia areata	8.000000e-21
GCST006585_1376	Blood protein levels	1.000000e-16
GCST006585_2731	Blood protein levels	9.000000e-37
GCST007932_58	Medication use (thyroid preparations)	3.000000e-08
GCST008916_1	Asthma	6.000000e-17
GCST009798_3	Asthma	1.000000e-17
GCST011053_3	Neuroblastoma (pediatric)	1.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007650	soluble interleukin-2 receptor subunit alpha measurement
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4106128 (PROTEIN-PROTEIN INTERACTION), CHEMBL4665592 (PROTEIN COMPLEX)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-2 receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
IL-15	Agonist	11.42	pKd

ChEMBL bioactivities

27 potent at pChembl≥5 of 43 total, top 27 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.10	IC50	800	nM	CHEMBL4079889
6.10	IC50	800	nM	CHEMBL4101389
6.10	IC50	800	nM	CHEMBL4085913
5.96	IC50	1100	nM	CHEMBL4066271
5.96	IC50	1100	nM	CHEMBL4069144
5.89	IC50	1300	nM	CHEMBL4093847
5.89	IC50	1300	nM	CHEMBL4066448
5.85	IC50	1400	nM	CHEMBL4063508
5.82	IC50	1500	nM	CHEMBL4085144
5.80	IC50	1600	nM	CHEMBL4096400
5.80	IC50	1600	nM	CHEMBL4066088
5.75	IC50	1800	nM	CHEMBL4087773
5.72	IC50	1900	nM	CHEMBL4103753
5.72	IC50	1900	nM	CHEMBL4093663
5.64	IC50	2300	nM	CHEMBL4079593
5.64	IC50	2300	nM	CHEMBL4074888
5.64	IC50	2300	nM	CHEMBL4101575
5.48	IC50	3300	nM	CHEMBL4065977
5.42	IC50	3800	nM	CHEMBL4067098
5.41	IC50	3900	nM	CHEMBL4088685
5.39	IC50	4100	nM	CHEMBL4079499
5.32	IC50	4800	nM	CHEMBL4070160
5.18	IC50	6600	nM	CHEMBL4096087
5.14	IC50	7300	nM	CHEMBL4083909
5.12	IC50	7600	nM	CHEMBL4082181
5.06	IC50	8700	nM	CHEMBL4088362
5.01	IC50	9800	nM	CHEMBL4060991

PubChem BioAssay actives

27 with measured affinity, of 108 total; 27 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
ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	0.8000	uM
(2,4-dichlorophenyl) 8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoate	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	0.8000	uM
N-(4-chlorophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	0.8000	uM
N-(2,4-dimethoxyphenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.1000	uM
8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-yloxyphenyl)octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.1000	uM
N-(2-hydroxy-4-methoxyphenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.3000	uM
N-(4-iodophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.3000	uM
N-(2,4-dibromophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfonyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.4000	uM
N-(2,4-dibromophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.5000	uM
N-(1-adamantyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.6000	uM
8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propoxyphenyl)octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.6000	uM
N-(4-azidophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.8000	uM
N-(2,4-dichlorophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.9000	uM
8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]-N-naphthalen-1-yloctanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	1.9000	uM
N-(2-chloro-4-methylphenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	2.3000	uM
N-(2,4-difluorophenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	2.3000	uM
N-(2,4-dichlorophenyl)-10-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]decanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	2.3000	uM
N-(2,4-dichlorophenyl)-11-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]undecanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	3.3000	uM
N-(1-adamantyl)-11-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]undecanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	3.8000	uM
N-(4-methoxyphenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	3.9000	uM
N-(2,4-dichlorophenyl)-6-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]hexanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	4.1000	uM
8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(2-methylpropoxy)phenyl]octanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	4.8000	uM
11-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]-N-naphthalen-1-ylundecanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	6.6000	uM
N-(2,4-dichlorophenyl)-16-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]hexadecanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	7.3000	uM
4-[(5-decylsulfanyl-4-methyl-1,2,4-triazol-3-yl)methyl]-2-methylphthalazin-1-one	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	7.6000	uM
(2,4-dichlorophenyl) 11-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]undecanoate	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	8.7000	uM
N-(2,4-dichlorophenyl)-4-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]butanamide	1446037: Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	ic50	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects cotreatment	3
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	2
Acetaminophen	increases expression, decreases expression	2
Methotrexate	decreases expression	2
Nickel	increases expression	2
bisphenol F	decreases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	increases expression	1
beta-hydroxy simvastatin acid	decreases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	decreases reaction, increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Permethrin	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4013726	Binding	Inhibition of human IL-15Ralpha-sushi domain/human IL-15-induced mouse 32D-beta cell proliferation preincubated for 30 mins with protein followed by cell addition measured after 2.5 days by Alamar blue reduction assay	Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1FY	Abcam A-549 IL15RA KO 1	Cancer cell line	Male
CVCL_B2NH	Abcam A-549 IL15RA KO 2	Cancer cell line	Male
CVCL_D7S2	Ubigene A-549 IL15RA KO	Cancer cell line	Male
CVCL_D8N3	Ubigene HCT 116 IL15RA KO	Cancer cell line	Male
CVCL_D9H1	Ubigene HEK293 IL15RA KO	Transformed cell line	Female
CVCL_E0EX	Ubigene HeLa IL15RA KO	Cancer cell line	Female

Clinical trials (associated diseases)

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