IL13

Summary

IL13 (interleukin 13, HGNC:5973) is a protein-coding gene on chromosome 5q31.1, encoding Interleukin-13 (P35225). Cytokine that plays important roles in allergic inflammation and immune response to parasite infection.

This gene encodes an immunoregulatory cytokine produced primarily by activated Th2 cells. This cytokine is involved in several stages of B-cell maturation and differentiation. It up-regulates CD23 and MHC class II expression, and promotes IgE isotype switching of B cells. This cytokine down-regulates macrophage activity, thereby inhibits the production of pro-inflammatory cytokines and chemokines. This cytokine is found to be critical to the pathogenesis of allergen-induced asthma but operates through mechanisms independent of IgE and eosinophils. This gene, IL3, IL5, IL4, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL4.

Source: NCBI Gene 3596 — RefSeq curated summary.

At a glance

• GWAS associations: 42
• Clinical variants (ClinVar): 15 total
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_002188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5973
Approved symbol	IL13
Name	interleukin 13
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	P600, IL-13, ALRH, BHR1, MGC116786, MGC116788, MGC116789
Ensembl gene	ENSG00000169194
Ensembl biotype	protein_coding
OMIM	147683
Entrez	3596

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 1 protein_coding, 1 retained_intron

ENST00000304506, ENST00000459878, ENST00000462480, ENST00000468334, ENST00000487267

RefSeq mRNA: 4 — MANE Select: NM_002188 NM_001354991, NM_001354992, NM_001354993, NM_002188

CCDS: CCDS4157

Canonical transcript exons

ENST00000304506 — 4 exons

Exon	Start	End
ENSE00001124031	132660175	132661110
ENSE00001124039	132658173	132658360
ENSE00003521747	132659724	132659828
ENSE00003591221	132659418	132659471

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 90.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9322 / max 419.2391, expressed in 33 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58489	0.9178	29
58488	0.0073	4
58487	0.0071	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.46	gold quality
right testis	UBERON:0004534	89.93	gold quality
testis	UBERON:0000473	87.02	gold quality
sperm	CL:0000019	81.15	gold quality
male germ cell	CL:0000015	79.66	silver quality
diaphragm	UBERON:0001103	74.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.52	gold quality
myocardium	UBERON:0002349	74.18	gold quality
pancreatic ductal cell	CL:0002079	74.10	silver quality
heart right ventricle	UBERON:0002080	71.86	gold quality
triceps brachii	UBERON:0001509	71.71	gold quality
parotid gland	UBERON:0001831	71.03	gold quality
gluteal muscle	UBERON:0002000	70.97	gold quality
frontal pole	UBERON:0002795	70.74	gold quality
paraflocculus	UBERON:0005351	69.54	gold quality
left ventricle myocardium	UBERON:0006566	69.13	gold quality
cardiac muscle of right atrium	UBERON:0003379	68.96	gold quality
middle frontal gyrus	UBERON:0002702	68.73	gold quality
vastus lateralis	UBERON:0001379	68.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	67.89	gold quality
quadriceps femoris	UBERON:0001377	67.87	gold quality
endometrium epithelium	UBERON:0004811	67.53	gold quality
orbitofrontal cortex	UBERON:0004167	66.56	gold quality
cartilage tissue	UBERON:0002418	66.47	gold quality
biceps brachii	UBERON:0001507	65.28	gold quality
vena cava	UBERON:0004087	64.85	silver quality
gingival epithelium	UBERON:0001949	64.48	gold quality
gingiva	UBERON:0001828	64.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	63.70	gold quality
esophagus squamous epithelium	UBERON:0006920	63.54	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	15125.95
E-ANND-3	no	1.46

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
AICDA	Activation
CD36	Activation
IDE	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, ATF2, ATF3, BHLHE41, CEBPB, CREB1, CTCF, E2F6, EGR1, ETS1, EZH2, FOS, GATA1, GATA2, GATA3, GFI1, GLI2, HAND2, IKZF1, IRF4, JUN, JUNB, KMT2A, MAF, MYB, MYC, NFATC1, NFATC2, NFIL3, NFKB, NR3C1, PPARG, SATB1, SPI1, STAT1, STAT3, STAT4, STAT5A, STAT5B

miRNA regulators (miRDB)

40 targeting IL13, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024

Literature-anchored findings (GeneRIF, showing 40)

• gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma (PMID:11709756)
• novel mechanism by which IFN-gamma can regulate IL-13 responses. (PMID:11786536)
• investigated a possible association of a variant of the IL-13 gene, with the immunologically hyper-reactive sowda form of onchocerciasis (PMID:11825773)
• The 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. (PMID:11830476)
• IL-13 has been implicated in the pathogenesis of asthma and in the regulation of IgE synthesis in humans. (PMID:11940068)
• variant might act as a functional genetic factor of bronchial asthma with a unique mechanism to upregulate local and systemic IL-13 concentration in vivo. (PMID:12063528)
• increased expression of IL-13 in CD4+ cell from patients with hyper-IgE could account, at least partly, for raised IgE levels in those individuals. (PMID:12067309)
• Eosinophils (but not neutrophils) produce and release functional IL-13 in allergic, infectious, and idiopathic eosinophilic diseases, as well as after in vitro exposure to GM-CSF or IL-5. (PMID:12097410)
• Review. The biologic activities of IL-13 in the immune system, the evidence implicating IL-13 as an autocrine growth factor for RS cells in Hodgkin’s disease, & the potential influence of IL-13 on the HD reactive inflammatory infiltrate are discussed. (PMID:12152987)
• Increased IL-13 but not IL-5 production by CD4-positive T cells and CD8-positive T cells in multiple sclerosis during relapse phase. (PMID:12163193)
• DNA methylation around the IL-4 and IL-13 genes before and after T cell differentiation (PMID:12165514)
• Alanine-scanning mutagenesis of the alpha-helix D segment reveals new functionally important residues (PMID:12189139)
• In lung fibroblasts IL13 induces the expression of the gamma c chain & its association with JAK3. In myofibroblasts, IL13 triggers formation of a new type of functional receptor (p-IL-4Ralpha /IL-13Ralpha 1/gamma c) & recruitment/phosphorylation of JAK3. (PMID:12207328)
• The receptor components and upstream signaling events initiated by IL-13 in primary human blood monocytes include: IL-4R(alpha), IL-2Rgammac, IL-13R(alpha)1 and IL-13R(alpha)2, Jak2, Tyk2, and Stat proteins 1alpha, 3, 5A, 5B, & 6. (PMID:12223527)
• Expression of IL-13 mRNA and the FMLP-induced release of IL-13 from basophils are both inhibited by preincubation of the cells with synthetic HIV-1 envelope gp41 peptides. (PMID:12370393)
• IL-13 in combination with TGF-beta 1 increases production of eotaxin-1 in airway fibroblasts from asthmatic and normal subjects. (PMID:12370400)
• eosinophils synthesize and store IL-13 (PMID:12377947)
• Adenovirus-mediated gene transfer of human IL-13 has cytoprotective functions in vitro, suggesting in vivo synergy of Ad-IL-13 and regulatory cells in the infectious transplantation tolerance pathway. Heme oxygenase-1 may be an IL-13 downstream effector. (PMID:12396617)
• modulates thymus and activation-regulated chemokine/CCL17 and interferon-induced protein of 10kDA/CXCL10 release by tumor necrosis factor-alpha and interferon-gamma in HaCaT cell line (PMID:12441140)
• 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)
• It was impossible to evaluate whether in vitro cytokine production profiles really can be deduced from a particular cytokine gene polymorphism. (PMID:12548511)
• Allele frequency of IL-13 polymorphism was not associated with rapid decline of lung function in smokers. (PMID:12594065)
• CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of this protein. (PMID:12654630)
• IL-13 synergistically augments eotaxin production by leukotriene C4 via up-regulation of CysLT1R expression on lung fibroblasts. (PMID:12682264)
• role in regulating vascular cell adhesion molecule-1 expression in human osteoblasts (PMID:12704784)
• Results provide evidence that interleukin-13 induces p38 MAP kinase phosphorylation and activation, which regulates Stat1 and Stat3 serine 727 phosphorylation. (PMID:12748293)
• IL13 is associated with diabetes mellitus, type 1 in Filipinos. (PMID:12748907)
• IL-13 is in part able to induce a mucus hypersecretory phenotype through a direct interaction with the airway epithelium and that MAP kinase and PtdIns 3-kinase signaling pathways are involved. (PMID:12794003)
• expression of alleles of the genes encoding IL-2, IL-3, IL-4, and IL-13 in CD4(+) T cell clones (PMID:12884288)
• Variants C-1055T and Arg130Gln of the interleukin 13 gene might play an important role on total serum IgE production. (PMID:12897746)
• IL-13 production was directly related to the level of Tax expression in the infected CD4+ T cells (PMID:12920029)
• There is a common IL-13 Arg130Gln single nucleotide polymorphism among Chinese atopy patients with allergic rhinitis. (PMID:12928861)
• These results suggest that MIP-T3 is a novel inhibitor of IL-13 signaling and may be a useful molecule in ameliorating various conditions in which IL-13 plays a central role. (PMID:12935900)
• data challenge the notion that acute graft-versus-host disease is purely a Th1-type cytokine-driven response, high-lighting a novel and highly significant link between the Th2-type cytokine IL-13 and aGVHD (PMID:14512310)
• interleukin-13 has emerged as promising means of improving allergic states, and several antagonists have been developed–REVIEW (PMID:14561191)
• Variant Gln110 associated with increased total serum IgE levels in atopy and was weakly associated with bronchial asthma. No association of variant with juvenile idiopathic arthritis(JIA). Variant Gln110 significantly less frequent in JIA. (PMID:14564352)
• IL-13 up-regulates SOCS-1 expression in A549 human lung adenocarcinoma cells by stimulating interaction of STAT6 with three interferon-gamma-activated sequence (GAS)motifs in the SOCS-1 promoter. (PMID:14634100)
• IL-13 up-regulates CD40L expression in normal human lung fibroblasts as well as fibroblasts from scarred lung tissue. (PMID:14734771)
• Decrease in blood levels observed after surgical removal of laryngeal squamous cell carcinoma. (PMID:14756548)
• These findings indicate that the CD38/cADPR-dependent pathway has a major role in IL-13-induced modulation of calcium signaling in human airway smooth muscle. (PMID:14764428)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il13	ENSMUSG00000020383
rattus_norvegicus	Il13	ENSRNOG00000007652

Protein

Protein identifiers

Interleukin-13 — P35225 (reviewed: P35225)

All UniProt accessions (1): P35225

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that plays important roles in allergic inflammation and immune response to parasite infection. Synergizes with IL2 in regulating interferon-gamma synthesis. Stimulates B-cell proliferation, and activation of eosinophils, basophils, and mast cells. Plays an important role in controlling IL33 activity by modulating the production of transmembrane and soluble forms of interleukin-1 receptor-like 1/IL1RL1. Displays the capacity to antagonize Th1-driven proinflammatory immune response and downregulates synthesis of many proinflammatory cytokines including IL1, IL6, IL10, IL12 and TNF through a mechanism that partially involves suppression of NF-kappa-B. Also functions on nonhematopoietic cells, including endothelial cells where it induces vascular cell adhesion protein 1/VCAM1, which is important in the recruitment of eosinophils. Exerts its biological effects through its receptors which comprises the IL4R chain and the IL13RA1 chain, to activate JAK1 and TYK2, leading to the activation of STAT6. Aside from IL13RA1, another receptor IL13RA2 acts as a high affinity decoy for IL13 and mediates internalization and depletion of extracellular IL13.

Subunit / interactions. Interacts with IL13RA2.

Subcellular location. Secreted.

Disease relevance. Allergic rhinitis (ALRH) [MIM:607154] A common disease with complex inheritance characterized by mucosal inflammation caused by allergen exposure. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the IL-4/IL-13 family.

RefSeq proteins (4): NP_001341920, NP_001341921, NP_001341922, NP_002179* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001325	IL-4/IL-13	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR018096	IL-4/IL-13_CS	Conserved_site
IPR020470	IL-13	Family

Pfam: PF03487

UniProt features (28 total): sequence conflict 8, helix 6, glycosylation site 4, strand 3, turn 2, disulfide bond 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3L5X	X-RAY DIFFRACTION	1.9
4I77	X-RAY DIFFRACTION	1.9
5L6Y	X-RAY DIFFRACTION	1.99
3L5W	X-RAY DIFFRACTION	2
4PS4	X-RAY DIFFRACTION	2.8
3BPO	X-RAY DIFFRACTION	3
5E4E	X-RAY DIFFRACTION	3
3LB6	X-RAY DIFFRACTION	3.05
3G6D	X-RAY DIFFRACTION	3.2
8BLQ	ELECTRON MICROSCOPY	3.97
1GA3	SOLUTION NMR
1IJZ	SOLUTION NMR
1IK0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35225-F1	86.01	0.58

Antibody-complex structures (SAbDab): 7 — 3G6D, 3L5W, 3L5X, 4I77, 4PS4, 5L6Y, 8BLQ

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): 62–90, 78–104

Glycosylation sites (4): 52, 63, 71, 86

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9012546	Interleukin-18 signaling
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 408 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, FUNG_IL2_SIGNALING_2, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_EPITHELIUM_DEVELOPMENT, MORF_FLT1, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, MORF_MSH3, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (35): microglial cell activation (GO:0001774), positive regulation of immunoglobulin production (GO:0002639), inflammatory response (GO:0006954), immune response (GO:0006955), response to nematode (GO:0009624), regulation of proton transport (GO:0010155), response to selenium ion (GO:0010269), positive regulation of gene expression (GO:0010628), positive regulation of B cell proliferation (GO:0030890), response to lipopolysaccharide (GO:0032496), positive regulation of interleukin-10 production (GO:0032733), response to nicotine (GO:0035094), interleukin-13-mediated signaling pathway (GO:0035772), macrophage activation (GO:0042116), positive regulation of macrophage activation (GO:0043032), positive regulation of mast cell degranulation (GO:0043306), response to ethanol (GO:0045471), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of smooth muscle cell proliferation (GO:0048661), positive regulation of protein secretion (GO:0050714), negative regulation of inflammatory response (GO:0050728), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), cellular response to mechanical stimulus (GO:0071260), negative regulation of transforming growth factor beta production (GO:0071635), positive regulation of cold-induced thermogenesis (GO:0120162), negative regulation of lung ciliated cell differentiation (GO:1901247), positive regulation of lung goblet cell differentiation (GO:1901251), negative regulation of complement-dependent cytotoxicity (GO:1903660), positive regulation of pancreatic stellate cell proliferation (GO:2000231), negative regulation of endothelial cell apoptotic process (GO:2000352), transforming growth factor beta receptor signaling pathway (GO:0007179), response to mechanical stimulus (GO:0009612), transforming growth factor beta1 production (GO:0032905), positive regulation of monoatomic ion transport (GO:0043270), cellular response to cytokine stimulus (GO:0071345)

GO Molecular Function (4): cytokine activity (GO:0005125), interleukin-13 receptor binding (GO:0005144), cytokine receptor binding (GO:0005126), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), external side of plasma membrane (GO:0009897)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Interleukins	1
Interleukin-1 family signaling	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macrophage activation	2
response to chemical	2
cellular anatomical structure	2
leukocyte activation involved in inflammatory response	1
glial cell activation	1
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
response to other organism	1
proton transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
positive regulation of cytokine production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-13	1
myeloid leukocyte activation	1
positive regulation of leukocyte activation	1
regulation of macrophage activation	1
positive regulation of leukocyte degranulation	1
mast cell degranulation	1
regulation of mast cell degranulation	1
response to alcohol	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
positive regulation of cell population proliferation	1

Protein interactions and networks

STRING

3386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL13	IL4R	P24394	999
IL13	IL13RA1	P78552	999
IL13	IL13RA2	Q14627	998
IL13	IL4	P05112	991
IL13	IL5	P05113	987
IL13	IFNG	P01579	960
IL13	IL10	P22301	953
IL13	STAT6	P42226	945
IL13	CCL11	P50877	941
IL13	IL33	O95760	938
IL13	IL17A	Q16552	936
IL13	CD4	P01730	932
IL13	IL9	P15248	932
IL13	TNF	P01375	931
IL13	IL6	P05231	930

IntAct

21 interactions, top by confidence:

A	B	Type	Score
IL13	IL13RA2	psi-mi:“MI:0407”(direct interaction)	0.800
IL13	IL13RA1	psi-mi:“MI:0407”(direct interaction)	0.800
IL13	IL13RA1	psi-mi:“MI:0915”(physical association)	0.800
IL13	IL13RA2	psi-mi:“MI:0915”(physical association)	0.800
IL13RA2	IL13	psi-mi:“MI:0915”(physical association)	0.800
IL13RA1	IL4R	psi-mi:“MI:0407”(direct interaction)	0.560
IL13	Il13ra2	psi-mi:“MI:0915”(physical association)	0.400
CFTR	IL13	psi-mi:“MI:0915”(physical association)	0.370
IL13	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
IL13	SPTB	psi-mi:“MI:0914”(association)	0.350
IL13	MYORG	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): IL13RA2 (Reconstituted Complex), IL13RA1 (Reconstituted Complex), IL4R (Reconstituted Complex), IL13 (Reconstituted Complex), IL13 (Reconstituted Complex), IL13RA2 (Reconstituted Complex), MAN1B1 (Affinity Capture-MS), MAP9 (Affinity Capture-MS), PLEKHG3 (Affinity Capture-MS), PPP1R9A (Affinity Capture-MS), C2CD5 (Affinity Capture-MS), FIBP (Affinity Capture-MS), CGN (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), IL13RA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A096P2H6, A0A0D9S1R4, A2APA5, A9CBA0, P06740, P06759, P0DKU6, P0DKW1, P0DKW2, P0DKW3, P0DKW4, P0DKY3, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP5, P0DUP6, P22749, P33622, P35225, P55056, P55057, P55797, Q0VCT2, Q13790, Q3SYR5, Q3ZRW9, Q5HZE8, Q5JTB6, Q5JX69, Q5JX71

Diamond homologs: P20109, P35225, P42203, P61126, Q5I6E4, Q864V6, Q865W5, Q865X3, Q95J68, Q9N0W9, Q9XSV9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
IL13	up-regulates	IL13RA1	binding
IL13	up-regulates	IL4R	binding
IL13	“up-regulates activity”	IL4R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

334 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132658357:GAAG:G	donor_gain	1.0000
5:132659416:A:AC	acceptor_loss	1.0000
5:132659416:A:AG	acceptor_gain	1.0000
5:132659416:AG:A	acceptor_gain	1.0000
5:132659417:G:GA	acceptor_gain	1.0000
5:132659417:GG:G	acceptor_gain	1.0000
5:132659417:GGCT:G	acceptor_gain	1.0000
5:132659417:GGCTC:G	acceptor_gain	1.0000
5:132659467:GCATG:G	donor_gain	1.0000
5:132659472:G:GA	donor_loss	1.0000
5:132659472:G:GG	donor_gain	1.0000
5:132659473:T:A	donor_loss	1.0000
5:132659720:A:AG	acceptor_gain	1.0000
5:132659720:ACAGT:A	acceptor_loss	1.0000
5:132659721:C:G	acceptor_gain	1.0000
5:132659721:CA:C	acceptor_loss	1.0000
5:132659722:A:AG	acceptor_gain	1.0000
5:132659722:A:G	acceptor_loss	1.0000
5:132659723:G:GG	acceptor_gain	1.0000
5:132659723:GT:G	acceptor_gain	1.0000
5:132659723:GTA:G	acceptor_gain	1.0000
5:132659723:GTAC:G	acceptor_gain	1.0000
5:132659723:GTACT:G	acceptor_gain	1.0000
5:132659826:GGG:G	donor_gain	1.0000
5:132659827:GG:G	donor_gain	1.0000
5:132659827:GGG:G	donor_gain	1.0000
5:132659828:GG:G	donor_gain	1.0000
5:132659829:G:GG	donor_gain	1.0000
5:132659830:TAAGG:T	donor_loss	1.0000
5:132660174:GCA:G	acceptor_gain	1.0000

AlphaMissense

947 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132659447:G:C	W68C	0.991
5:132659447:G:T	W68C	0.991
5:132659427:T:A	C62S	0.987
5:132659428:G:C	C62S	0.987
5:132660236:T:C	L132P	0.986
5:132659746:T:C	L84P	0.982
5:132659763:T:C	C90R	0.982
5:132658335:T:C	L50P	0.980
5:132659427:T:C	C62R	0.980
5:132659428:G:A	C62Y	0.980
5:132659763:T:A	C90S	0.978
5:132659764:G:C	C90S	0.978
5:132659429:C:G	C62W	0.977
5:132659445:T:A	W68R	0.976
5:132659445:T:C	W68R	0.976
5:132659794:T:C	L100P	0.972
5:132658323:T:C	L46P	0.968
5:132660207:A:C	K122N	0.968
5:132660207:A:T	K122N	0.968
5:132659428:G:T	C62F	0.967
5:132659764:G:A	C90Y	0.967
5:132659765:C:G	C90W	0.967
5:132659734:C:A	A80D	0.966
5:132659794:T:A	L100Q	0.962
5:132659441:G:A	M66I	0.952
5:132659441:G:C	M66I	0.952
5:132659441:G:T	M66I	0.952
5:132660206:A:T	K122I	0.951
5:132659794:T:G	L100R	0.950
5:132658335:T:A	L50Q	0.948

dbSNP variants (sampled 300 via entrez): RS1000169601 (5:132659612 C>T), RS1000447544 (5:132655926 G>A,C), RS1000978586 (5:132660576 C>T), RS1001232679 (5:132661251 T>C), RS1001382053 (5:132655363 A>G), RS1001579345 (5:132660901 A>G), RS1001955051 (5:132656838 T>A,G), RS1002392966 (5:132656491 C>G,T), RS1002523322 (5:132657163 A>C), RS1003398740 (5:132657992 C>T), RS10044025 (5:132655429 T>C,G), RS1004597784 (5:132655366 A>G), RS1004803420 (5:132654797 C>G), RS1005303103 (5:132660155 C>G), RS1005767044 (5:132660450 C>A,T)

Disease associations

OMIM: gene MIM:147683 | disease phenotypes: MIM:600807, MIM:607154

GenCC curated gene-disease

Mondo (2): inherited susceptibility to asthma (MONDO:0010940), allergic rhinitis, susceptibility to (MONDO:0100177)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001426	Non-Mendelian inheritance
HP:0002099	Asthma
HP:0032933	Airway hyperresponsiveness
HP:4000007	Bronchoconstriction

GWAS associations

42 associations (top):

Study	Trait	p-value
GCST000322_4	Psoriasis	5.000000e-15
GCST000804_1	Asthma	1.000000e-07
GCST001316_3	IgE levels	3.000000e-18
GCST001387_1	Hodgkin’s lymphoma	1.000000e-08
GCST001709_5	Atopic dermatitis	2.000000e-06
GCST001725_83	Inflammatory bowel disease	1.000000e-52
GCST002100_2	Atopic dermatitis	2.000000e-17
GCST002275_6	Asthma (childhood onset)	2.000000e-06
GCST002480_3	Hodgkin’s lymphoma	2.000000e-11
GCST002737_2	Atopic dermatitis	5.000000e-09
GCST002738_12	Psoriasis	5.000000e-06
GCST002874_13	Psoriasis	5.000000e-09
GCST003184_20	Atopic dermatitis	7.000000e-12
GCST003184_32	Atopic dermatitis	4.000000e-17
GCST003268_16	Psoriasis vulgaris	3.000000e-14
GCST003269_5	Cutaneous psoriasis	3.000000e-08
GCST003990_18	Allergy	6.000000e-10
GCST004866_29	Alopecia areata	5.000000e-09
GCST005038_125	Allergic disease (asthma, hay fever or eczema)	4.000000e-21
GCST005038_60	Allergic disease (asthma, hay fever or eczema)	2.000000e-24
GCST005212_28	Asthma	5.000000e-16
GCST005213_2	Asthma (childhood onset)	2.000000e-09
GCST005527_7	Psoriasis	3.000000e-10
GCST005790_51	Rosacea symptom severity	3.000000e-09
GCST006408_15	Allergic sensitization	5.000000e-07
GCST006409_25	Allergic rhinitis	2.000000e-09
GCST006862_12	Asthma	1.000000e-14
GCST007562_2	Asthma	1.000000e-11
GCST007564_14	Asthma or allergic disease (pleiotropy)	4.000000e-11
GCST008916_34	Asthma	2.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0007773	cutaneous psoriasis measurement
EFO:0009180	rosacea severity measurement
EFO:0005298	allergic sensitization measurement
EFO:0007614	asthma exacerbation measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580486 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1295686	Efficacy	3	Hepatitis vaccines
rs1800925	Toxicity	3	sunitinib	Renal Cell Carcinoma

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs20541	IL13		0.00	0
rs1295686	IL13	3	2.25	1	Hepatitis vaccines
rs1800925	IL13	3	2.25	1	sunitinib
rs848	IL13		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases expression, increases activity, affects reaction, affects cotreatment, increases reaction (+4 more)	9
Lipopolysaccharides	increases secretion, affects expression, increases reaction, affects activity, increases expression (+5 more)	8
Vehicle Emissions	affects reaction, increases expression, affects cotreatment, decreases expression, increases abundance	7
Resveratrol	decreases reaction, increases expression, increases secretion, decreases secretion, decreases response to substance (+2 more)	4
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression, affects expression, affects secretion (+3 more)	3
sodium arsenite	decreases expression, increases expression	2
Calcimycin	affects cotreatment, increases expression, decreases reaction	2
Dexamethasone	decreases reaction, increases secretion, increases expression	2
Glutathione	affects cotreatment, decreases reaction, increases secretion, decreases abundance, decreases secretion	2
Hydrogen Peroxide	increases abundance, decreases reaction, increases expression, affects cotreatment	2
Nickel	increases expression	2
Silicon Dioxide	increases expression, increases secretion	2
Cadmium Chloride	decreases reaction, increases expression, increases secretion	2
coagulin-L	decreases reaction, increases expression	1
TL8-506	affects cotreatment, increases secretion	1
fulvic acid	affects cotreatment, decreases reaction, increases expression	1
titanium dioxide	increases expression	1
9-(2-hydroxy-3-nonyl)adenine	decreases reaction, increases secretion	1
fisetin	decreases reaction, increases expression, affects cotreatment	1
butyraldehyde	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
Amb a I protein, Ambrosia artemisiifolia	affects cotreatment, increases expression	1
butylbenzyl phthalate	decreases expression	1
chlorobenzene	increases expression, increases reaction	1
benzyl isothiocyanate	decreases reaction, increases expression	1
8-(4-sulfophenyl)theophylline	decreases reaction, increases secretion, decreases secretion	1
Ribomunyl	affects cotreatment, increases expression	1
gadolinium chloride	increases expression	1
phthalic anhydride	increases expression	1
epinastine	decreases expression	1

Clinical trials (associated diseases)

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