IL5

Summary

IL5 (interleukin 5, HGNC:6016) is a protein-coding gene on chromosome 5q31.1, encoding Interleukin-5 (P05113). Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils.

This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31.

Source: NCBI Gene 3567 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 16 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Drug target: yes — 3 curated mechanism-of-action drugs; 1 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 2 — Mepolizumab, Reslizumab
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_000879
• Interaction hub: 2,986 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6016
Approved symbol	IL5
Name	interleukin 5
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	IL-5, EDF, TRF
Ensembl gene	ENSG00000113525
Ensembl biotype	protein_coding
OMIM	147850
Entrez	3567

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

MANE Select: ENST00000231454

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 5: 1

ENST00000231454, ENST00000450655, ENST00000462418, ENST00000877569, ENST00001138923

RefSeq mRNA: 1 — MANE Select: NM_000879 NM_000879

CCDS: CCDS4156

Canonical transcript exons

ENST00000231454 — 4 exons

Exon	Start	End
ENSE00000763102	132543094	132543126
ENSE00000763103	132542015	132542143
ENSE00000854387	132541445	132541909
ENSE00000854388	132543335	132543522

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 73.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7288 / max 528.1124, expressed in 29 samples.

Highest expression (Bgee): testis, calcaneal tendon, tendon, uterine tube, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

IL5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.6e-02	-0.71	5:132560079:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
63338	0.6930	17
63339	0.0358	12

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	73.67	gold quality
left testis	UBERON:0004533	72.33	gold quality
testis	UBERON:0000473	69.93	gold quality
calcaneal tendon	UBERON:0003701	64.00	gold quality
tendon	UBERON:0000043	62.67	gold quality
right uterine tube	UBERON:0001302	62.21	gold quality
sperm	CL:0000019	60.51	gold quality
tendon of biceps brachii	UBERON:0008188	60.48	silver quality
pancreatic ductal cell	CL:0002079	60.23	silver quality
male germ cell	CL:0000015	59.86	gold quality
lower lobe of lung	UBERON:0008949	59.05	silver quality
buccal mucosa cell	CL:0002336	54.88	gold quality
left ventricle myocardium	UBERON:0006566	54.30	gold quality
corpus callosum	UBERON:0002336	53.51	gold quality
smooth muscle tissue	UBERON:0001135	53.13	gold quality
granulocyte	CL:0000094	52.92	gold quality
nasal cavity epithelium	UBERON:0005384	52.36	gold quality
right ovary	UBERON:0002118	51.72	gold quality
epithelial cell of pancreas	CL:0000083	51.24	gold quality
quadriceps femoris	UBERON:0001377	50.81	gold quality
right coronary artery	UBERON:0001625	50.76	gold quality
metanephros	UBERON:0000081	50.45	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
vastus lateralis	UBERON:0001379	50.38	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	50.27	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
myocardium	UBERON:0002349	49.98	gold quality
thoracic aorta	UBERON:0001515	49.74	gold quality
ascending aorta	UBERON:0001496	49.70	gold quality
uterine cervix	UBERON:0000002	49.64	gold quality
left ovary	UBERON:0002119	49.63	gold quality
metanephros cortex	UBERON:0010533	49.57	gold quality
fallopian tube	UBERON:0003889	49.42	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
aorta	UBERON:0000947	49.29	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
tonsil	UBERON:0002372	49.24	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.11	gold quality
popliteal artery	UBERON:0002250	49.05	gold quality
oviduct epithelium	UBERON:0004804	49.00	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
tibial artery	UBERON:0007610	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
thymus	UBERON:0002370	48.41	gold quality
ovary	UBERON:0000992	48.30	gold quality
muscle tissue	UBERON:0002385	48.25	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
cerebellar cortex	UBERON:0002129	48.13	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cerebellar hemisphere	UBERON:0002245	48.05	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
ectocervix	UBERON:0012249	47.95	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
myometrium	UBERON:0001296	47.91	gold quality
body of uterus	UBERON:0009853	47.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	47.82	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
cerebellum	UBERON:0002037	47.62	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
lower esophagus	UBERON:0013473	47.55	gold quality
kidney epithelium	UBERON:0004819	47.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	47.52	gold quality
sural nerve	UBERON:0015488	47.27	gold quality
skeletal muscle tissue	UBERON:0001134	47.25	gold quality
ileal mucosa	UBERON:0000331	47.21	silver quality
left coronary artery	UBERON:0001626	47.21	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
coronary artery	UBERON:0001621	47.09	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
skin of hip	UBERON:0001554	46.74	silver quality
deltoid	UBERON:0001476	46.58	gold quality
gall bladder	UBERON:0002110	46.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	46.47	gold quality
mucosa of stomach	UBERON:0001199	46.24	gold quality
cranial nerve II	UBERON:0000941	46.20	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	46.14	gold quality
endocervix	UBERON:0000458	45.90	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
adenohypophysis	UBERON:0002196	45.75	gold quality
left uterine tube	UBERON:0001303	45.54	gold quality
uterus	UBERON:0000995	45.42	gold quality
descending thoracic aorta	UBERON:0002345	45.39	gold quality
rectum	UBERON:0001052	45.37	gold quality
sigmoid colon	UBERON:0001159	45.35	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
muscle organ	UBERON:0001630	45.11	gold quality
synovial joint	UBERON:0002217	44.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	31001.64
E-CURD-84	yes	1139.79
E-ANND-3	no	2.23

HPA expression

RNA tissue specificity: Tissue enriched

52 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	6.4
Testis	tissue	4.8	not detected
Hippocampus	tissue	4.6	not detected
Locus coeruleus	tissue	3.8
Nucleus accumbens	tissue	3.4
Choroid plexus	tissue	2.7
Cerebellum	tissue	2.4	not detected
Olfactory bulb	tissue	2.3
Amygdala	tissue	1.6
Cerebral cortex	tissue	1.4	not detected
Retrosplenial and cingulate cortex	tissue	1.4
Retrosplenial cortex	tissue	1.4
Septum	tissue	1.3
Insular cortex	tissue	1.3
Prefrontal cortex	tissue	1.2
Basal ganglia	tissue	1.2	not detected
Hippocampal formation	tissue	1.2
Entorhinal cortex	tissue	1.2
Occipital cortex	tissue	1.2
Hypothalamus	tissue	1.1
Periaqueductal gray	tissue	1.1
Temporal cortex	tissue	1.1
Motor cortex	tissue	1.0
Putamen	tissue	1.0
Midbrain	tissue	1.0
Corpus callosum	tissue	1.0
Ventral forebrain	tissue	1.0
Substantia nigra	tissue	0.9
Somatosensory cortex	tissue	0.9
Medulla oblongata	tissue	0.8
Thalamus	tissue	0.8
Small intestine	tissue	0.8	not detected
Spinal cord	tissue	0.8
Pons	tissue	0.7
Superior colliculi	tissue	0.7
Gallbladder	tissue	0.5	not detected
Duodenum	tissue	0.5	not detected
Thyroid gland	tissue	0.3	not detected
Fallopian tube	tissue	0.3	not detected
Stomach 1	tissue	0.2	not detected
Retina	tissue	0.2
Frontal cortex	tissue	0.2
Liver	tissue	0.2	not detected
Heart muscle	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Rectum	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Prostate	tissue	0.1	not detected
Tonsil	tissue	0.1	not detected
Appendix	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Flocculonodular lobe (9.3), Area parastriata, inferior (8.3), Vermis (8.3), Hippocampus, CA3 (8.0), Orbitofrontal gyrus, anterior (7.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BCL6, BHLHE41, CEBPA, CEBPB, CEBPG, CTCF, ELF1, EOMES, EP300, ETS1, ETS2, FOS, FOSL2, FOXA2, FOXA3, FOXC1, GATA1, GATA2, GATA3, GATA4, GFI1, HAND1, HAND2, HDAC4, HMGB1, HNF4A, IRF1, IRF6, JUN, JUNB, JUND, KAT7, LEF1, MAF, MYB, NFAM1, NFATC1, NFATC2, NFATC3

miRNA regulators (miRDB)

Targeting IL5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

20 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-647	97.73	67.79	927
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-2276-5P	96.27	65.85	937

Functional genomics

gnomAD constraint: pLI 0.0213, LOEUF 1.07, missense Z 0.186 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000231454 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 40)

• inhibition of signaling by antisense oligodeoxynucleotides targeting the common beta chain of receptors (PMID:11763346)
• data indicate that ability to produce the type 2 cytokines IL-13 and IL-5 defines CD161(+) NK cells at intermediate stages of differentiation, and is lost upon terminal functional differentiation, concomitant with acquired ability to produce IFN-gamma (PMID:11830476)
• CD4(+) T cells are the major source of IL-5 among CD3(+) lymphocytes in atopic asthmatic subjects, whereas in nonatopic asthmatic subjects CD8 (+) T cells as well as CD4(+) T cells contribute to the increased production of IL-5 (PMID:11842300)
• By itself, IL5 increases nerve growth factor level in eosinophils, but in combination with immune complexes, significantly reduces eosinophil NGF levels. (PMID:11877300)
• in asthma Il-5 might directly induce bronchial hyperresponsiveness (PMID:11897983)
• A putative Bcl6-binding silencer element has been identified in the 3’ untranslated region of IL-5 cDNA. (PMID:12097386)
• the AP-1 complex plays a key role in regulating IL5 expression- this provides an explanation for the sensitivity of IL5 to protein synthesis inhibitors and a mechanism for the specific induction of IL5 compared with other cytokines. (PMID:12354764)
• expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in patients with cicatricial pemphigoid (PMID:12366695)
• Constitutive overexpression of human IL-5 in transgenic mice induces migration of bone marrow progenitor cells to the spleen and extramedullary hematopoiesis in the spleen. (PMID:12393708)
• IL-5 down-modulates its receptor via a proteinase-mediated process. (PMID:12444155)
• Protease allergen Der p1 and the secreted proteases of the hookworm Necator americanus are able to directly induce type 2 cytokines IL-4, IL-5, and IL-13 by basophils, that could promote IgE synthesis, eosinophil recruitment, and Th2 cells. (PMID:12525574)
• Increased IL-5 expression in muscle of eosinophilic myositis patients correlates with the presence of activated eosinophilic granules and the release of eosinophilic major basic protein in muscle biopsy specimens. (PMID:12534990)
• This is the first evidence of an association between the IL5 gene polymorphism and bronchial asthma (PMID:12575459)
• Incubation of eosinophils with IL-5 leads to reduced expression of IL-5R alpha, which is sustained for up to 5 days; eosinophil IL-3R alpha expression is increased by IL-5, whereas GM-CSF receptor alpha expression is not affected by IL-5. (PMID:12759409)
• IL-5 gene transcription in human asthmatic peripheral T cells in vivo clearly demonstrate that an interaction with monocytes enhances IL-5 gene transcription. (PMID:12771545)
• 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)
• Results show that the expression of interleukin-5 mRNA in mild asthma differed from that in severe and moderate asthma before and after corticosteroid treatment. (PMID:12910312)
• IL-5 and eotaxin are associated with acute exacerbation of asthma. (PMID:12915771)
• Hematopoietin receptor superfamily. Comprised of cytokine-specific alpha chain and common beta chain for signaling. Contributes to differentiation and function of leukocytes. Protective immunity and pathophysiology of immunologic diseases. Review. (PMID:14564341)
• IL5 gene may play a role in blood eosinophilia associated with atopic dermatitis (PMID:14581138)
• Results identify several transcriptional targets of interleukin-5 and granulocyte macrophage-colony-stimulating factor in human eosinophils and suggest that a number of protein products are critical to the responsiveness of airway eosinophils. (PMID:14630612)
• skin mast cells precultured in the presence of IL-4 [alone or plus stem cell factor (SCF)] before anti-IgE stimulation, acquired the ability to produce IL-5, and IL-1beta was concomitantly suppressed (PMID:14634065)
• Significantly higher levels were found in soluble egg antigen-stimulated PBMC from schistosomiasis mansoni patients with degree III hepatic fibrosis compared to patients with degree I or II fibrosis, and in patients untreated for 1 year. (PMID:15155645)
• histone acetyltransferase (HAT) activity of CBP/p300 was required to activate IL-5 expression (PMID:15271374)
• exposure of human mast cells to IL-4, IL-5, and IFN-gamma during growth and differentiation generally down-regulated mast cell number and function (PMID:15367434)
• IL-5 induces the protein expression of cyclin D3 and the kinase Pim-1, both of which are regulated by STAT-dependent processes in airway and blood eosinophils. (PMID:15528381)
• IL-5 acts as a triggering factor in the toxiallergic complaints commonly seen in helminth and protozoon infections. (PMID:15534922)
• Up-regulated by a conserved upstream enhancer with two potential GATA-3-binding sites (PMID:15549733)
• GATA-3 contributed to the production of IL-4, IL-5 in patients with allergic rhinitis. (PMID:15563083)
• extracellular signal-regulated kinase-mediated adhesion of beta(2)-integrin caused by IL-5 is mediated in human eosinophils by a class IA PI3K through activation of a PKCdelta pathway (PMID:15802551)
• analysis of IL5 induction of activation of the multisubunit receptor system using an interleukin-5 mimetic peptide (PMID:15826943)
• interleukin-5 transcription repression by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment (PMID:15826950)
• Topical steroid treatment may suppress IL-5 gene expression, and steroids may inhibit eosinophil functions in nasal polyps. (PMID:15835818)
• Allergen-specific T cell lines induced in the presence of salmeterol and fluticasone proprionate inhibited IL-5 and IL-13 production by allergen-specific Th2 cell lines in an IL-10-dependent manner (PMID:15845862)
• Interleukin 5 plays a role in colonic carcinogenesis from ulcerative colitis by interacting with IGF-II. (PMID:15935984)
• Polymorphisms in the IL5 gene were associated with each other in whites and African Americans. (PMID:15951665)
• This Th2 cytokine is possibly involved in the modulation of lung graft transplantation tolerance. (PMID:15964392)
• These data suggest that during a respiratory virus infection activated CD8+ T cells from asthmatic subjects may produce excess type 2 cytokines and may contribute to asthma exacerbation by augmenting allergic inflammation. (PMID:16001979)
• Eosinophils from asthmatics release IL-5 in an autocrine fashion to act on their own IL-5 receptors in prevention of apoptosis through the upregulation of Bcl-2 expression. (PMID:16036415)
• Sputum IL-13, but not IL-5, is inversely correlated with the provocative concentration of a substance causing a 20% fall in FEV1 for methacholine in asthmatic patients (PMID:16236836)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il5	ENSMUSG00000036117
rattus_norvegicus	Il5	ENSRNOG00000008111

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96557) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 39 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased neutrophil cell number	2
granulomatous inflammation	2
increased eosinophil cell number	2
increased leukocyte cell number	1
increased monocyte cell number	1
enlarged heart	1
abnormal mast cell morphology	1
alopecia	1
rectal prolapse	1
abnormal liver morphology	1
abnormal spleen morphology	1
enlarged lymph nodes	1
spontaneous skin ulceration	1
increased body weight	1
increased metastatic potential	1
abnormal mating receptivity	1
abnormal susceptibility to infection	1
premature death	1
decreased airway responsiveness	1
abnormal mast cell physiology	1
abnormal eosinophil differentiation	1
decreased IgE level	1
increased liver weight	1
peritoneal inflammation	1
liver fibrosis	1

+14 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	P48093	98.5%	Diamond
Bos taurus	P52173	97.0%	Diamond
Ovis aries	Q28586	97.0%	Diamond
Cercocebus atys	P46685	95.5%	Diamond
Sigmodon hispidus	Q9ESI9	90.0%	Diamond
Meriones unguiculatus	Q62575	89.3%	Diamond
Equus caballus	O02699	87.3%	Diamond
Felis catus	O77515	87.3%	Diamond
Sus scrofa	Q9MYM5	87.3%	Diamond
Canis lupus familiaris	Q95J76	85.1%	Diamond
Cavia porcellus	O08987	74.8%	Diamond
Notamacropus eugenii	Q9XT91	60.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TH2LCRR	ncRNA	101927761
IL4-AS1	ncRNA	105379176
IL4	protein-coding	3565
IL13	protein-coding	3596
IRF1	protein-coding	3659
RAD50	protein-coding	10111
MIR3936	ncRNA	100500865
CARINH	ncRNA	441108
MIR3936HG	ncRNA	553103
SLC22A5	protein-coding	6584
LINC02863	ncRNA	102723741
KIF3A	protein-coding	11127

Protein

Protein identifiers

Interleukin-5 — P05113 (reviewed: P05113)

Alternative names: B-cell differentiation factor I, Eosinophil differentiation factor, T-cell replacing factor

All UniProt accessions (2): P05113, C9JQP9

UniProt curated annotations — full annotation on UniProt →

Function. Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils. Also acts on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation. Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB. Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with IL5RA. Interacts with CSF2RB.

Subcellular location. Secreted.

Tissue specificity. Present in peripheral blood mononuclear cells.

Similarity. Belongs to the IL-5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P05113-1	1	yes
P05113-2	2, delta2, hIL-5delta2

RefSeq proteins (1): NP_000870* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000186	IL-5	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily

Pfam: PF02025

UniProt features (18 total): helix 6, strand 3, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
9GVN	DEPEMOKIMAB FAB IN COMPLEX WITH INTERLEUKIN 5	X-RAY DIFFRACTION	1.93
1HUL	A NOVEL DIMER CONFIGURATION REVEALED BY THE CRYSTAL STRUCTURE AT 2.4 ANGSTROMS RESOLUTION …	X-RAY DIFFRACTION	2.4
3QT2	Structure of a cytokine ligand-receptor complex	X-RAY DIFFRACTION	2.55
3VA2	Crystal structure of human Interleukin-5 in complex with its alpha receptor	X-RAY DIFFRACTION	2.7
8TLD	Structure of the IL-5 Signaling Complex	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05113-F1	87.07	0.76

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Biotech drugs

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
90	not glycosylated

Disulfide bonds (2)

Type	Positions
Interchain (with c-105)	63
Interchain (with c-63)	105

Glycosylation sites (2)

Type	Positions
O-linked (galnac…) threonine	22
N-linked (glcnac…) asparagine	47

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-912526	Interleukin receptor SHC signaling	curated
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	electronic
R-HSA-168256	Immune System	—
R-HSA-451927	Interleukin-2 family signaling	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 268 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, FUNG_IL2_SIGNALING_2, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_PODOSOME_ASSEMBLY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_B_CELL_PROLIFERATION, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, PID_REG_GR_PATHWAY

GO Biological Process (13): positive regulation of immunoglobulin production (GO:0002639), inflammatory response (GO:0006954), immune response (GO:0006955), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of B cell proliferation (GO:0030890), interleukin-5-mediated signaling pathway (GO:0038043), positive regulation of eosinophil differentiation (GO:0045645), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), positive regulation of podosome assembly (GO:0071803), signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (4): cytokine activity (GO:0005125), interleukin-5 receptor binding (GO:0005137), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), plasma membrane (GO:0005886)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by Interleukins	2
MAPK1/MAPK3 signaling	1
Interleukin-2 family signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
Differentiation of T cells	1
Immune System	1
Cytokine Signaling in Immune system	1
Signal Transduction	1
MAPK family signaling cascades	1

GO top-level categories

42 GO namespaces:

Category	Terms
receptor ligand activity	2
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
defense response	1
immune system process	1
response to stimulus	1
cell surface receptor signaling pathway via STAT	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
cytokine-mediated signaling pathway	1
eosinophil differentiation	1
positive regulation of granulocyte differentiation	1
regulation of eosinophil differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
positive regulation of protein-containing complex assembly	1
podosome assembly	1
regulation of podosome assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cytokine receptor binding	1
growth factor receptor binding	1
binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
cell surface receptor signaling pathway via JAK-STAT	BP	direct assay
interleukin-5-mediated signaling pathway	BP	direct assay
positive regulation of podosome assembly	BP	direct assay
positive regulation of receptor signaling pathway via JAK-STAT	BP	direct assay
extracellular region	CC	direct assay
cytokine activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,986 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL5	IL13	P35225	984
IL5	IL4	P05112	980
IL5	IFNG	P01579	960
IL5	CSF2	P04141	956
IL5	IL3	P08700	952
IL5	IL33	O95760	938
IL5	IL2	P01585	933
IL5	CD4	P01730	931
IL5	TNF	P01375	930
IL5	IL6	P05231	929
IL5	CCL11	P50877	929
IL5	IL10	P22301	928
IL5	IL17A	Q16552	928
IL5	IL5RA	Q01344	926
IL5	IL1B	P01584	920

IntAct

Human interaction partners of IL5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
IL5RA	direct interaction	0.620	6
CSF2RB	physical association	0.520	2

BioGRID (10 interactions; top human partners by supporting records): IL5RA (Reconstituted Complex; 5 records), S100A6 (Reconstituted Complex), S100P (Reconstituted Complex)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
IL5	up-regulates	AKT1
Degranulation	“up-regulates quantity”	IL5
IL5	up-regulates	IL5RA	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ IL-5 receptor-IL-5 complex, high affinity	3	CSF2RB, IL5, IL5RA

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CSF2RB;IL5RA	ligand	Signaling by Interleukin

Disease & clinical

Genetic variants

Variant evidence for IL5: 16 ClinVar records (0 pathogenic / likely pathogenic); 10 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	2
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 115):

Position(s)	Effect	Δscore	Sites
5:132541910–132541911	acceptor_loss	1.0000	6
5:132541912	acceptor_gain	1.0000
5:132543333–132543334	donor_loss	1.0000	5
5:132543127–132543128	acceptor_loss	0.9900	6
5:132543092–132543093	donor_loss	0.9800	5
5:132542013–132542014	donor_loss	0.9700	5
5:132542144–132542145	acceptor_loss	0.9700	6
5:132542976	acceptor_gain	0.9700
5:132543092	donor_loss	0.9700
5:132542013	donor_loss	0.9600

AlphaMissense

143 missense substitutions predicted likely pathogenic (of 866 scored), across 43 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F115	7	0.936	0.984
C63	7	0.934	0.962
F122	7	0.891	0.982
F68	7	0.887	0.953
C105	7	0.873	0.935
F88	7	0.853	0.930
N90	6	0.721	0.813
T33	5	0.707	0.872
P55	5	0.677	0.789
L123	4	0.834	0.927
W130	4	0.834	0.853
K95	4	0.820	0.906
G70	4	0.818	0.908
I67	4	0.699	0.822
E66	4	0.610	0.734
L119	3	0.915	0.975
L37	3	0.897	0.919
L44	3	0.881	0.887
L74	3	0.858	0.864
I52	3	0.846	0.920

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:147850 | disease phenotypes:

GWAS associations

10 associations:

Study	Trait	p-value
GCST90002381_86	Eosinophil count	8e-148
GCST001725_83	Inflammatory bowel disease	1e-52
GCST008916_45	Asthma	6e-32
GCST009798_82	Asthma	1e-26
GCST009798_88	Asthma	9e-24
GCST005975_11	Eosinophil count	9e-19
GCST000339_3	Eosinophil count	1e-10
GCST003097_14	Pediatric autoimmune diseases	2e-9
GCST008916_84	Asthma	2e-9
GCST005790_25	Rosacea symptom severity	5e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0009180	rosacea severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1169600 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the IL5 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
MEPOLIZUMAB	Antibody	4
RESLIZUMAB	Antibody	4
DEPEMOKIMAB	Antibody	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 73,656 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1370	BUDESONIDE	4	73,656

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2069812	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Efficacy	Genotypes AA + AG is associated with increased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Spondylitis, Ankylosing as compared to genotype GG.	PMID:36361964

Binding affinities (BindingDB)

2 measured of 3 human assays (3 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5440921	IC50	2000 nM
CHEMBL2377405	IC50	4000 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	IC50	2000	nM	CHEMBL5440921
5.40	IC50	4000	nM	CHEMBL2377405

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
7-methyl-2-methylidenefuro[3,2-h]isoquinolin-3-one	2005357: Inhibition of IL-5 (unknown origin)	ic50	2.0000	uM
5-(cyclohexylmethoxy)-3-[3-hydroxy-3-(4-hydroxyphenyl)propyl]chromen-4-one	2038001: Inhibition of IL-5 (unknown origin)	ic50	4.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dexamethasone	decreases expression, decreases reaction, decreases secretion, decreases stability, affects cotreatment (+1 more)	10
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression, increases secretion	7
nickel sulfate	increases secretion, decreases reaction	5
Vehicle Emissions	affects cotreatment, increases expression, decreases expression, decreases secretion, increases abundance	5
Particulate Matter	affects cotreatment, increases expression, increases secretion, decreases reaction, decreases secretion (+1 more)	5
Calcimycin	decreases reaction, affects abundance, affects chemical synthesis, increases reaction, affects cotreatment (+1 more)	4
Lipopolysaccharides	decreases expression, affects cotreatment, increases secretion, affects response to substance, increases expression	4
Tacrolimus	decreases reaction, increases expression, decreases expression, affects cotreatment	4
Cyclosporine	decreases reaction, increases secretion, affects cotreatment, increases expression, decreases expression	4
Nickel	increases expression, increases secretion	3
Ozone	affects cotreatment, increases expression, decreases expression	3
Tretinoin	decreases activity, decreases reaction, increases expression	3
Ionomycin	affects cotreatment, decreases reaction, increases expression, increases secretion	3
kaempferol	decreases expression, decreases reaction, increases expression, affects cotreatment	2
bisphenol A	decreases expression, decreases methylation	2
Amb a I protein, Ambrosia artemisiifolia	increases expression, decreases reaction, affects cotreatment	2
montelukast	affects cotreatment, decreases expression	2
Fluticasone	decreases expression, decreases reaction, increases expression	2
Terbinafine	decreases expression, decreases reaction, decreases secretion	2
Atrazine	decreases expression	2
Beclomethasone	increases secretion, decreases expression, decreases reaction, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Ketoconazole	decreases secretion, decreases expression, decreases reaction	2
Miconazole	decreases expression, decreases reaction, decreases secretion	2
Nitric Oxide	affects cotreatment, increases abundance, decreases secretion	2
Prednisone	decreases expression	2
Quercetin	decreases reaction, increases expression, affects cotreatment, decreases expression	2
Ribavirin	decreases expression, decreases secretion	2
Tolnaftate	decreases expression, decreases reaction, decreases secretion	2
1-Methyl-3-isobutylxanthine	decreases expression, decreases reaction, decreases secretion, increases abundance, increases reaction	2

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1177154	Binding	Inhibition of interleukin-5 at 50 uM	Design and synthesis of novel hydroxyalkylaminomethylchromones for their IL-5 inhibitory activity. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for IL5 across ~30M SureChEMBL compounds — explore on Sugi Predict.