IL1RN

Summary

IL1RN (interleukin 1 receptor antagonist, HGNC:6000) is a protein-coding gene on chromosome 2q14.1, encoding Interleukin-1 receptor antagonist protein (P18510). Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A.

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 3557 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sterile multifocal osteomyelitis with periostitis and pustulosis (Strong, GenCC)
• GWAS associations: 28
• Clinical variants (ClinVar): 258 total — 11 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• MANE Select transcript: NM_173842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6000
Approved symbol	IL1RN
Name	interleukin 1 receptor antagonist
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	IL1RA, ICIL-1RA, IL1F3, IRAP, IL-1RN, MGC10430
Ensembl gene	ENSG00000136689
Ensembl biotype	protein_coding
OMIM	147679
Entrez	3557

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000259206, ENST00000354115, ENST00000361779, ENST00000409052, ENST00000409930, ENST00000463073, ENST00000465812, ENST00000472292, ENST00000486167, ENST00000696879, ENST00000696880, ENST00000696881, ENST00000696882, ENST00000696883

RefSeq mRNA: 6 — MANE Select: NM_173842 NM_000577, NM_001318914, NM_001379360, NM_173841, NM_173842, NM_173843

CCDS: CCDS2113, CCDS2114, CCDS2115, CCDS46396

Canonical transcript exons

ENST00000409930 — 4 exons

Exon	Start	End
ENSE00000925698	113129576	113129664
ENSE00001071190	113131045	113131157
ENSE00001584157	113127598	113127740
ENSE00003968750	113132656	113134014

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.93.

FANTOM5 (CAGE): breadth broad, TPM avg 228.2889 / max 18933.0746, expressed in 641 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22099	212.7978	346
22095	10.6423	335
22094	4.0634	341
22093	0.7780	229
22088	0.0075	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.93	gold quality
buccal mucosa cell	CL:0002336	99.85	gold quality
palpebral conjunctiva	UBERON:0001812	99.80	gold quality
tongue squamous epithelium	UBERON:0006919	99.76	gold quality
pharyngeal mucosa	UBERON:0000355	99.74	gold quality
esophagus squamous epithelium	UBERON:0006920	99.74	gold quality
gingiva	UBERON:0001828	99.60	gold quality
oral cavity	UBERON:0000167	99.57	gold quality
gingival epithelium	UBERON:0001949	99.56	gold quality
squamous epithelium	UBERON:0006914	99.55	gold quality
esophagus mucosa	UBERON:0002469	99.42	gold quality
body of tongue	UBERON:0011876	99.36	gold quality
epithelium of esophagus	UBERON:0001976	99.03	gold quality
periodontal ligament	UBERON:0008266	98.64	gold quality
cervix squamous epithelium	UBERON:0006922	98.60	gold quality
amniotic fluid	UBERON:0000173	98.58	gold quality
cervix epithelium	UBERON:0004801	98.48	gold quality
tongue	UBERON:0001723	97.79	gold quality
skin of abdomen	UBERON:0001416	97.03	gold quality
pancreatic ductal cell	CL:0002079	96.43	gold quality
skin of leg	UBERON:0001511	96.37	gold quality
penis	UBERON:0000989	96.30	gold quality
zone of skin	UBERON:0000014	96.16	gold quality
upper leg skin	UBERON:0004262	95.94	gold quality
blood	UBERON:0000178	95.85	gold quality
mammalian vulva	UBERON:0000997	95.84	gold quality
monocyte	CL:0000576	95.38	gold quality
right lobe of liver	UBERON:0001114	95.36	gold quality
superior surface of tongue	UBERON:0007371	95.31	gold quality
leukocyte	CL:0000738	95.01	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	6244.16
E-GEOD-86618	yes	799.06
E-CURD-114	yes	312.61
E-HCAD-1	yes	265.22
E-CURD-46	yes	20.57
E-HCAD-10	yes	15.58
E-MTAB-7381	no	2185.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF2, CEBPB, CEBPG, FOS, GLI2, IL10, IRF6, JUN, MEF2A, NFATC1, NFE2L2, NFKB1, NFKB, NR5A2, NRF1, PPARA, RELA, SPI1, STAT3, STAT6, ZHX2

miRNA regulators (miRDB)

62 targeting IL1RN, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-516B-5P	99.56	66.33	1495

Literature-anchored findings (GeneRIF, showing 40)

• The serum level of IL-1Ra is higher in cicatricial pemphigoid patients in prolonged clinical remission and following intravenous immunogloglobulin therapy, when compared to the pre-IVIg treatment level. (PMID:11448121)
• There were no significant differences in the distributions of the IL-1RN and IL-1B genotpes, allele frequencies or halotypes. (PMID:11686217)
• There is an association between urolithiasis and polymorphism in the IL-1Ra gene. (PMID:11762793)
• Septic shock whole-blood leukocytes and neutrophils (PMNs) selectively maintained production of sIL-1RA after treatment with LPS. (PMID:11770040)
• Interleukin-1 receptor antagonist (IL-1Ra) gene VNTR polymorphism was studied in children with DSM-IV ADHD and their parents to determine the role of brain cytokine activity in the etiopathogenesis of ADHD. (PMID:11803448)
• Slight association of mutations with hypertension. (PMID:11840488)
• results suggest that polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata (PMID:11841485)
• A borderline association was observed between il-1rn and patchy alopecia areata. (PMID:11841553)
• In dengue shock syndrome pts, IL-1Ra was significantly associated with F1+2, TATc (p < 0.04 and p < 0.02, respectively). IL1RA is involved in the onset and regulation of hemostasis. (PMID:11858187)
• Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion of IL-1 receptor antagonist by epithelial cells. (PMID:11876744)
• IL-1RN*2 homozygotes had a 6.47-fold increased rate of death from sepsis. Insufficient production of IL-1RN might contribute to this higher mortality. (PMID:11876758)
• Interleukin-1 receptor antagonist gene polymorphism in chinese patients with systemic lupus erythematosus. (PMID:12111633)
• There are associations of spontaneous preterm delivery with the fetal carriage of IL1B+3953*1 and IL1RN*2 alleles in African and Hispanic populations, respectively. (PMID:12114904)
• Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis. (PMID:12115182)
• The polymorphism of IL1RN genes 1/2 and 2/2 are associated with the susceptibility of gastric cancer in Chinese. (PMID:12133467)
• IL1RN production is regulated by ligands of the peroxisome proliferator-activated receptor gamma (PMID:12160520)
• Review. The balance between IL-1 & IL-1Ra in local tissues plays an important role in many diseases. An allelic polymorphism has been associated with a variety of human diseases primarily of epithelial & endothelial cell origin. (PMID:12220547)
• Women carrying the A2 allele of the IL-1ra gene showed greater BMD in the lumbar spine and hip. (PMID:12240899)
• important genetic regulator of constitutive, as well as LPS-stimulated, IL-1beta release (PMID:12355453)
• polymorphisms are associated with generalized early onset periodontitis in Japanese (PMID:12445219)
• investigated interleukin polymorphisms in ovarian cancer but did not find any association between common polymorphisms of interleukin 1A, interleukin 1B, and interleukin 1 receptor antagonist and the occurrence of ovarian cancer (PMID:12445604)
• In NIDDM patients, allele 2 carriers had an increased prevalence of CAD that remained significant in a multivariate logistic regression model. Variable number tandem repeat (VNTR) polymorphism in intron 2. (PMID:12453918)
• Investigation of the possible association of a polymorphism in the interleukin-1 receptor antagonist gene with the severity of Plasmodium falciparum malaria in Ghanaian children. (PMID:12472674)
• Pregnant women who are colonized with U. urealyticum during the first trimester have elevated vaginal IL-1ra concentrations and a higher prevalence of the IL-1RN*2 homozygote genotype than do noncolonized women (PMID:12496176)
• a “defective” IL-1ra response to IL-1 may underlie, at least in part, the exaggerated prostaglandin-endoperoxide H synthase (PGHS)-2 induction in orbital fibroblasts (PMID:12519748)
• The polymorphism of IL-1RA seems to be involved in the induction of different solid tumors. (PMID:12530098)
• spontaneous release of IL-8 and IL-1ra by airway neutrophils was significantly higher than that from blood neutrophils in cystic fibrosis (PMID:12547728)
• women with recurrent spontaneous abortion showed a significantly increased frequency of genotypes bearing the rare allele IL1RN*3 (PMID:12609525)
• allele 2 of the IL-1ra gene represents a susceptibility factor in the development of carotid atherosclerosis; A gene-dose effect was detected - The homozygous carrier state for allele 2 was associated with greater likelihood of atherosclerosis (PMID:12624309)
• intracellular IL-1Ra1, which is released into the extracellular space when overexpressed under the control of a strong constituitive promoter in transgenic mice has a similar anti-arthritic effect as secreted IL-1Ra (PMID:12645941)
• It was concluded that the lower expression of icIL-1ra in CML marrow nucleated cells might be involved in the evolution of CML. (PMID:12667286)
• serum interleukin-1 receptor antagonist was strongly associated with regional fat distribution, and especially truncal fat mass, both at baseline and during treatment in Cushing’s syndrome (PMID:12679428)
• Data suggest that IL-1ra may have a function connected with endothelial cell (EC) growth. (PMID:12764021)
• In multiple sclerosis primary progressive patients, the IL-1beta /IL-1ra ratio was significantly lower than in relapsing-remitting patients. (PMID:12775358)
• Increased serum level of interleukin-1 receptor antagonist is associated with children with Langerhans cell histiocytosis (PMID:12794527)
• polymorphic in women with cervical cancer. (PMID:12820354)
• highly significant ankylosing spondylitis association with markers in the IL1RN gene (PMID:12847695)
• IL-1Ra is not helpful in predicting (POAG) primary open-angle glaucoma in Chinese patients. (PMID:12913327)
• a possible epistatic effect between tumour necrosis factor and IL1RN linked genes for susceptibility to palmoplantar pustulosis (PMID:12919285)
• When analyzed separately, none of the IL1B or IL1RN polymorphisms was associated either with inflammation or restenosis. However, when the IL-1B (-511) and the IL-1RN VNTR genotypes were combined, a highly significant relationship was observed. (PMID:12958619)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	il1fma	ENSDARG00000089383
danio_rerio	il1b	ENSDARG00000098700
mus_musculus	Il1rn	ENSMUSG00000026981
rattus_norvegicus	Il1rn	ENSRNOG00000005871

Paralogs (7): IL1B (ENSG00000125538), IL37 (ENSG00000125571), IL36G (ENSG00000136688), IL36A (ENSG00000136694), IL36RN (ENSG00000136695), IL36B (ENSG00000136696), IL1F10 (ENSG00000136697)

Protein

Protein identifiers

Interleukin-1 receptor antagonist protein — P18510 (reviewed: P18510)

Alternative names: ICIL-1RA, IL1 inhibitor

All UniProt accessions (2): P18510, A0A8Q3WMN6

UniProt curated annotations — full annotation on UniProt →

Function. Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A. Protects from immune dysregulation and uncontrolled systemic inflammation triggered by IL1 for a range of innate stimulatory agents such as pathogens.

Subcellular location. Secreted Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. The intracellular form of IL1RN is predominantly expressed in epithelial cells.

Disease relevance. Microvascular complications of diabetes 4 (MVCD4) [MIM:612628] Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Chronic recurrent multifocal osteomyelitis 2, with periostitis and pustulosis (CRMO2) [MIM:612852] An autosomal recessive, autoinflammatory disease of skin and bone resulting in sterile multifocal osteomyelitis, periostitis, and pustulosis from birth. The term autoinflammatory disease describes a group of disorders characterized by attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T-cells. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the IL-1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P18510-1	1	yes
P18510-2	2, icIL-1ra
P18510-3	3, icIL-1ra type II
P18510-4	4

RefSeq proteins (6): NP_000568, NP_001305843, NP_001366289, NP_776213, NP_776214, NP_776215 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000975	IL-1_fam	Family
IPR003297	IL-1RA/IL-36	Family
IPR008996	IL1/FGF	Homologous_superfamily
IPR020877	IL-1_CS	Conserved_site

Pfam: PF00340

UniProt features (27 total): strand 13, helix 3, turn 3, splice variant 3, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1ILT	X-RAY DIFFRACTION	2
1ILR	X-RAY DIFFRACTION	2.1
1IRA	X-RAY DIFFRACTION	2.7
2IRT	X-RAY DIFFRACTION	3.2
1IRP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18510-F1	86.98	0.78

Functional residue map

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

Disulfide bonds (1): 91–141

Glycosylation sites (1): 109

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6783783	Interleukin-10 signaling
R-HSA-9020702	Interleukin-1 signaling

MSigDB gene sets: 530 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, PEREZ_TP63_TARGETS, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_REGULATION_OF_HETEROTYPIC_CELL_CELL_ADHESION, MODULE_45, GOBP_INSULIN_SECRETION, PID_IL1_PATHWAY, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_HORMONE_TRANSPORT, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN

GO Biological Process (10): lipid metabolic process (GO:0006629), acute-phase response (GO:0006953), inflammatory response (GO:0006954), immune response (GO:0006955), insulin secretion (GO:0030073), negative regulation of heterotypic cell-cell adhesion (GO:0034115), response to glucocorticoid (GO:0051384), negative regulation of interleukin-1-mediated signaling pathway (GO:2000660), negative regulation of cytokine-mediated signaling pathway (GO:0001960), signal transduction (GO:0007165)

GO Molecular Function (8): cytokine activity (GO:0005125), interleukin-1 receptor binding (GO:0005149), interleukin-1, type I receptor binding (GO:0005150), interleukin-1, type II receptor binding (GO:0005151), interleukin-1 receptor antagonist activity (GO:0005152), interleukin-1 type I receptor antagonist activity (GO:0045352), interleukin-1 type II receptor antagonist activity (GO:0045353), protein binding (GO:0005515)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cytoplasm (GO:0005737), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
Interleukin-1 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of cytokine-mediated signaling pathway	2
cytokine receptor binding	2
interleukin-1 receptor binding	2
interleukin-1 receptor antagonist activity	2
primary metabolic process	1
acute inflammatory response	1
defense response	1
immune system process	1
response to stimulus	1
protein secretion	1
peptide hormone secretion	1
negative regulation of cell-cell adhesion	1
heterotypic cell-cell adhesion	1
regulation of heterotypic cell-cell adhesion	1
regulation of cell-cell adhesion involved in gastrulation	1
response to corticosteroid	1
interleukin-1-mediated signaling pathway	1
regulation of interleukin-1-mediated signaling pathway	1
regulation of cytokine-mediated signaling pathway	1
negative regulation of signal transduction	1
cytokine-mediated signaling pathway	1
negative regulation of response to cytokine stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
growth factor receptor binding	1
interleukin-1 binding	1
receptor antagonist activity	1
binding	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

2444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL1RN	IL1R1	P14778	997
IL1RN	IL1A	P01583	988
IL1RN	IL1B	P01584	952
IL1RN	IL1R2	P27930	915
IL1RN	IL6	P05231	913
IL1RN	CXCL8	P10145	897
IL1RN	IL10	P22301	874
IL1RN	CRP	P02741	867
IL1RN	TNF	P01375	813
IL1RN	IL18	Q14116	772
IL1RN	NLRP3	Q96P20	757
IL1RN	CASP1	P29466	751
IL1RN	IL4	P05112	740
IL1RN	CCL3	P10147	738
IL1RN	CCL5	P13501	722

IntAct

50 interactions, top by confidence:

A	B	Type	Score
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
IL1RN	IL1R1	psi-mi:“MI:0407”(direct interaction)	0.610
IL1R1	IL1RN	psi-mi:“MI:0915”(physical association)	0.610
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
IL1RN	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
RFK	IL1RN	psi-mi:“MI:0915”(physical association)	0.400
IL1RN	GPIHBP1	psi-mi:“MI:0915”(physical association)	0.400
IL1RN	BTBD1	psi-mi:“MI:0915”(physical association)	0.400
IL1RN	POT1	psi-mi:“MI:0915”(physical association)	0.370
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
RIPPLY3	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRXL2A	A2ML1	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
FCF1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
SEC22C	ACADS	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
RNF115	IGLC7	psi-mi:“MI:0914”(association)	0.350
PIGT	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS), COPS3 (Co-fractionation), COPS3 (Far Western), COPS4 (Reconstituted Complex), GPS1 (Affinity Capture-Western), IL1RN (Affinity Capture-Western), IL1RN (Affinity Capture-Western), IL1RN (Affinity Capture-MS), IL1RN (Affinity Capture-MS)

ESM2 similar proteins: A4UYK8, G1SRW8, O18999, O77482, P01584, P03969, P0C7P3, P10749, P13109, P14628, P15655, P18510, P20003, P25085, P25086, P26889, P26890, P41687, P46648, P48090, P48800, P51493, P70380, P79182, P97636, Q14116, Q28292, Q28386, Q29056, Q2HZH0, Q63264, Q6PUD2, Q6R2X3, Q865X8, Q866R8, Q8IXQ6, Q8QFQ8, Q8R460, Q8WNR2, Q9BEH0

Diamond homologs: O18999, O77482, P09428, P18510, P21621, P25085, P25086, P26890, P51745, P79162, Q29056, Q2MH07, Q866R8, Q8R459, Q8WNR2, Q8WWZ1, Q9BEH0, Q9D6Z6, Q9GMZ4, Q9NZH6, Q9QYY1, Q9UBH0, Q9UHA7, Q9YGD3, A4UYK8, P01584, P10749, P14628, P26889, P41687, P46648, P48090, P51493, P79182, Q28292, Q28386, Q2HZH0, Q63264, Q6PUD2, Q6R2X3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
IL10	“up-regulates quantity by expression”	IL1RN	“transcriptional regulation”
NfKb-p65/p50	“up-regulates quantity by expression”	IL1RN	“transcriptional regulation”
STAT3	“up-regulates quantity by expression”	IL1RN	“transcriptional regulation”
IL1RN	“down-regulates activity”	IL1R1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	5
Uncertain significance	102
Likely benign	73
Benign	41

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
14675	NM_173842.3(IL1RN):c.229G>T (p.Glu77Ter)	Pathogenic
14676	NM_173842.3(IL1RN):c.160C>T (p.Gln54Ter)	Pathogenic
14678	NC_000002.12:g.112960554_113135775del	Pathogenic
1942385	NM_173842.3(IL1RN):c.133C>T (p.Gln45Ter)	Pathogenic
253541	GRCh37/hg19 2q12.3-14.1(chr2:109556627-117570152)x1	Pathogenic
2731291	NM_173841.3(IL1RN):c.52G>T (p.Glu18Ter)	Pathogenic
2821013	NM_173841.3(IL1RN):c.25G>T (p.Glu9Ter)	Pathogenic
3247349	NC_000002.11:g.(?113875596)(113875625_?)del	Pathogenic
660820	NM_173842.3(IL1RN):c.213_227del (p.Asp72_Ile76del)	Pathogenic
832163	NC_000002.12:g.(?113116893)(113135016_?)del	Pathogenic
97905	NM_173842.3(IL1RN):c.156_157del (p.Asn52fs)	Pathogenic
1694277	NM_173841.3(IL1RN):c.10+2T>C	Likely pathogenic
2629610	NM_173842.3(IL1RN):c.141del (p.Phe48fs)	Likely pathogenic
3069200	NM_173842.3(IL1RN):c.46del (p.Leu16fs)	Likely pathogenic
444516	NM_173842.3(IL1RN):c.62C>G (p.Ser21Ter)	Likely pathogenic
559539	NM_173842.3(IL1RN):c.63A>G (p.Ser21=)	Likely pathogenic

SpliceAI

349 predictions. Top by Δscore:

Variant	Effect	Δscore
2:113127738:CAG:C	donor_loss	1.0000
2:113127739:AG:A	donor_loss	1.0000
2:113127741:G:A	donor_loss	1.0000
2:113129570:TTTCA:T	acceptor_loss	1.0000
2:113129571:TTCAG:T	acceptor_loss	1.0000
2:113129574:A:AG	acceptor_gain	1.0000
2:113129574:A:AT	acceptor_loss	1.0000
2:113129575:G:GT	acceptor_gain	1.0000
2:113129575:GA:G	acceptor_gain	1.0000
2:113129661:GAAG:G	donor_gain	1.0000
2:113129663:AGG:A	donor_loss	1.0000
2:113131040:CCCAG:C	acceptor_loss	1.0000
2:113131042:CA:C	acceptor_loss	1.0000
2:113131043:A:AG	acceptor_gain	1.0000
2:113131043:AG:A	acceptor_loss	1.0000
2:113131044:G:GT	acceptor_gain	1.0000
2:113131044:GAA:G	acceptor_gain	1.0000
2:113131044:GAAA:G	acceptor_gain	1.0000
2:113131044:GAAAA:G	acceptor_gain	1.0000
2:113131153:TGGAG:T	donor_loss	1.0000
2:113131154:GGAGG:G	donor_loss	1.0000
2:113131155:G:GT	donor_gain	1.0000
2:113131155:GAGGT:G	donor_loss	1.0000
2:113131156:AGGT:A	donor_loss	1.0000
2:113131157:GGT:G	donor_loss	1.0000
2:113131158:GT:G	donor_loss	1.0000
2:113131159:T:G	donor_loss	1.0000
2:113132646:T:TA	acceptor_gain	1.0000
2:113132654:A:AG	acceptor_gain	1.0000
2:113132654:AG:A	acceptor_gain	1.0000

AlphaMissense

1176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:113132704:T:C	F123L	0.991
2:113132706:C:A	F123L	0.991
2:113132706:C:G	F123L	0.991
2:113132804:T:A	V156D	0.988
2:113132710:T:C	F125L	0.986
2:113132712:C:A	F125L	0.986
2:113132712:C:G	F125L	0.986
2:113132744:T:C	F136S	0.984
2:113132848:T:C	F171L	0.983
2:113132850:C:A	F171L	0.983
2:113132850:C:G	F171L	0.983
2:113132711:T:C	F125S	0.979
2:113129583:G:C	D42H	0.978
2:113129629:C:A	A57D	0.976
2:113132849:T:C	F171S	0.975
2:113129585:T:A	D42E	0.974
2:113129585:T:G	D42E	0.974
2:113129584:A:T	D42V	0.970
2:113132711:T:G	F125C	0.968
2:113132770:T:C	F145L	0.965
2:113132772:C:A	F145L	0.965
2:113132772:C:G	F145L	0.965
2:113127736:T:C	F38L	0.964
2:113127738:C:A	F38L	0.964
2:113127738:C:G	F38L	0.964
2:113129584:A:C	D42A	0.964
2:113129578:T:C	I40T	0.961
2:113132743:T:C	F136L	0.959
2:113132745:T:A	F136L	0.959
2:113132745:T:G	F136L	0.959

dbSNP variants (sampled 300 via entrez): RS1000155892 (2:113113684 C>G,T), RS1000281962 (2:113133570 A>T), RS1000283096 (2:113121431 T>C), RS1000309293 (2:113118882 C>A,G,T), RS1000434545 (2:113127808 C>G,T), RS1000499371 (2:113112163 C>T), RS1000567620 (2:113113397 T>A,C), RS1000664320 (2:113132409 C>T), RS1000764834 (2:113123619 G>A), RS1000822593 (2:113126422 T>G), RS1000831505 (2:113098337 C>T), RS1000933796 (2:113129312 C>T), RS1001088642 (2:113102067 C>G,T), RS1001221721 (2:113120556 T>C,G), RS1001315262 (2:113120256 G>A,T)

Disease associations

OMIM: gene MIM:147679 | disease phenotypes: MIM:612852, MIM:613659, MIM:612628, MIM:178500

GenCC curated gene-disease

Disease	Classification	Inheritance
sterile multifocal osteomyelitis with periostitis and pustulosis	Strong	Autosomal recessive

Mondo (5): sterile multifocal osteomyelitis with periostitis and pustulosis (MONDO:0013021), gastric cancer (MONDO:0001056), microvascular complications of diabetes, susceptibility to, 4 (MONDO:0012966), autoinflammatory syndrome (MONDO:0019751), interstitial lung disease 2 (MONDO:0800497)

Orphanet (4): Sterile multifocal osteomyelitis with periostitis and pustulosis (Orphanet:210115), Autoinflammatory syndrome (Orphanet:93665), Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000885	Broad ribs
HP:0000904	Flaring of rib cage
HP:0000938	Osteopenia
HP:0000962	Hyperkeratosis
HP:0000988	Skin rash
HP:0001270	Motor delay
HP:0001386	Joint swelling
HP:0001442	Typified by somatic mosaicism
HP:0001531	Failure to thrive in infancy
HP:0001744	Splenomegaly
HP:0002098	Respiratory distress
HP:0002206	Pulmonary fibrosis
HP:0002240	Hepatomegaly
HP:0002754	Osteomyelitis
HP:0002797	Osteolysis
HP:0002829	Arthralgia
HP:0002949	Fused cervical vertebrae
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003623	Neonatal onset
HP:0010280	Stomatitis
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011897	Increased total neutrophil count
HP:0012126	Stomach cancer
HP:0025092	Epidermal acanthosis
HP:0025116	Fetal distress
HP:0025615	Abscess
HP:0040165	Periostitis
HP:0200039	Pustule
HP:0410067	Increased level of L-fucose in urine

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000189_34	Protein quantitative trait loci	7.000000e-06
GCST001650_9	C-reactive protein	9.000000e-10
GCST001762_7	Obesity-related traits	2.000000e-06
GCST002147_10	Fibrinogen	6.000000e-19
GCST002987_16	Stroke	6.000000e-07
GCST003927_5	Dysmenorrheic pain	7.000000e-07
GCST004121_21	Fibrinogen levels	4.000000e-24
GCST004122_36	Fibrinogen levels	2.000000e-23
GCST004613_80	Sum neutrophil eosinophil counts	2.000000e-21
GCST004614_130	Granulocyte count	2.000000e-21
GCST004620_44	Sum basophil neutrophil counts	2.000000e-20
GCST004626_18	Myeloid white cell count	4.000000e-20
GCST004629_23	Neutrophil count	7.000000e-21
GCST004632_132	Lymphocyte percentage of white cells	4.000000e-09
GCST004633_107	Neutrophil percentage of white cells	5.000000e-11
GCST006585_2683	Blood protein levels	1.000000e-06
GCST011350_13	C-reactive protein levels	4.000000e-10
GCST011878_4	Mitochondrial heteroplasmy measurement	1.000000e-15
GCST012198_3	Interleukin-6 levels	2.000000e-11
GCST012480_10	C-reactive protein levels	2.000000e-07
GCST012616_15	Spondylosis	5.000000e-06
GCST90002389_123	Lymphocyte percentage of white cells	5.000000e-27
GCST90002391_139	Mean corpuscular hemoglobin concentration	6.000000e-11
GCST90002394_8	Monocyte percentage of white cells	2.000000e-16
GCST90002399_157	Neutrophil percentage of white cells	5.000000e-33
GCST90002404_23	Red cell distribution width	2.000000e-10
GCST90011899_81	Aspartate aminotransferase levels	5.000000e-16
GCST90011900_170	Serum alkaline phosphatase levels	9.000000e-21

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004754	interleukin 1 receptor antagonist measurement
EFO:0004458	C-reactive protein measurement
EFO:0004626	IGFBP-3 measurement
EFO:0007889	dysmenorrheic pain measurement
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0600008	mitochondrial heteroplasmy measurement
EFO:0004810	interleukin-6 measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007989	monocyte percentage of leukocytes
EFO:0009188	Red cell distribution width
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C557815	Deficiency of interleukin-1 receptor antagonist (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523191 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4251961	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Ulcerative Colitis

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4251961	IL1RN	3	2.75	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs55663133	IL1RN		0.00	0
rs62158854	IL1RN		0.00	0
rs55709272	IL1RN		0.00	0
rs7580634	IL1RN		0.00	0
rs62158853	IL1RN		0.00	0
rs419598	IL1RN		0.00	0

ChEMBL bioactivities

74 potent at pChembl≥5 of 92 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL4101200
8.70	IC50	2	nM	CHEMBL5517929
8.30	IC50	5.012	nM	CHEMBL1277623
8.19	IC50	6.5	nM	CHEMBL5191661
8.11	IC50	7.7	nM	CHEMBL4455644
7.96	Ki	10.9	nM	CHEMBL1277623
7.89	IC50	13	nM	CHEMBL5209483
7.80	IC50	15.85	nM	CHEMBL1277623
7.75	IC50	18	nM	CHEMBL1277623
7.72	IC50	19	nM	CHEMBL5195885
7.62	Ki	23.7	nM	CHEMBL4762305
7.52	IC50	30	nM	CHEMBL3416733
7.50	IC50	32	nM	CHEMBL4537224
7.47	IC50	34	nM	CHEMBL1852487
7.41	IC50	39	nM	CHEMBL4762305
7.14	Ki	72.44	nM	CHEMBL6192511
7.09	Ki	81.28	nM	ANGIOTENSIN IV
7.08	IC50	84	nM	CHEMBL5558123
6.92	IC50	120	nM	CHEMBL1852660
6.82	IC50	150	nM	CHEMBL5194003
6.80	IC50	160	nM	CHEMBL5183817
6.73	IC50	186	nM	CHEMBL5527891
6.70	Ki	200.5	nM	CHEMBL4753417
6.70	IC50	200	nM	CHEMBL5195928
6.66	IC50	218	nM	CHEMBL3827468
6.62	IC50	240	nM	CHEMBL5199194
6.60	IC50	251.2	nM	ANGIOTENSIN IV
6.59	IC50	259	nM	CHEMBL5191661
6.57	IC50	270	nM	CHEMBL5209535
6.55	IC50	280	nM	CHEMBL5207828
6.48	IC50	330	nM	CHEMBL4753417
6.48	IC50	330	nM	CHEMBL5171198
6.46	IC50	344	nM	CHEMBL5512491
6.44	IC50	360	nM	CHEMBL5200376
6.42	IC50	383	nM	CHEMBL5512459
6.41	IC50	390	nM	CHEMBL5197001
6.34	IC50	460	nM	CHEMBL5185614
6.29	IC50	510	nM	CHEMBL5194823
6.25	IC50	560	nM	CHEMBL5555425
6.17	Ki	674.4	nM	CHEMBL4745618
6.09	IC50	820	nM	CHEMBL5184077
6.08	IC50	830	nM	CHEMBL5202569
6.05	Ki	887	nM	CHEMBL4787513
5.96	IC50	1110	nM	CHEMBL4745618
5.90	Ki	1252	nM	CHEMBL4778960
5.89	Ki	1300	nM	CHEMBL4527760
5.84	IC50	1460	nM	CHEMBL4787513
5.82	IC50	1500	nM	CHEMBL5189714
5.76	IC50	1754	nM	CHEMBL4070078
5.72	IC50	1900	nM	CHEMBL5182525

PubChem BioAssay actives

72 with measured affinity, of 119 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]pent-4-ynyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1524644: Inhibition of human IRAP using L-leucine 7-amido-4-methyl coumarin substrate by microplate fluorescence reader based assay	ic50	0.0020	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]but-3-ynyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.0020	uM
2-[2-[[[(4R,8S,11S)-11-amino-8-[(4-hydroxyphenyl)methyl]-6,10-dioxo-1,2-dithia-5,9-diazacyclotridecane-4-carbonyl]amino]methyl]phenyl]acetic acid	1664906: Inhibition of human IRAP soluble domain expressed in HEK293S GnTI(-) cells using Leu-AMC as substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0050	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-(4-hydroxyphenoxy)butanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.0065	uM
[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1524644: Inhibition of human IRAP using L-leucine 7-amido-4-methyl coumarin substrate by microplate fluorescence reader based assay	ic50	0.0077	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(4-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.0130	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-(3,4,5-trifluorophenoxy)butanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.0190	uM
(4R,8S,11S)-11-amino-N-[[2-(2-amino-2-oxoethyl)phenyl]methyl]-8-[(4-hydroxyphenyl)methyl]-6,10-dioxo-1,2-dithia-5,9-diazacyclotridecane-4-carboxamide	1694954: Binding affinity to recombinant full length human IRAP expressed in HEK293T cells using Leu-MCA as substrate	ki	0.0237	uM
[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.0300	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-5,5-diphenylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1524644: Inhibition of human IRAP using L-leucine 7-amido-4-methyl coumarin substrate by microplate fluorescence reader based assay	ic50	0.0320	uM
7-amino-1,4-dibromo-5,7,8,9-tetrahydrobenzo[7]annulen-6-one	2066908: Inhibition of human recombinant IRAP expressed in baculovirus infected Sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ic50	0.0340	uM
(3S)-N-hydroxy-4-(4-hydroxyphenyl)-3-[5-[[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]butanamide	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.0840	uM
7-amino-1-bromo-4-phenyl-5,7,8,9-tetrahydrobenzo[7]annulen-6-one	2066908: Inhibition of human recombinant IRAP expressed in baculovirus infected Sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ic50	0.1200	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(4-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.1500	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(4-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.1600	uM
(2S)-N-hydroxy-3-(4-methoxyphenyl)-2-[4-[[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]propanamide	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.1860	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-5-(3-chlorophenoxy)-2-hydroxypentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.2000	uM
(4R,8S,11S)-11-amino-N-[[2-(2-amino-2-oxoethyl)phenyl]methyl]-8-[(4-fluorophenyl)methyl]-6,10-dioxo-1,2-dithia-5,9-diazacyclotridecane-4-carboxamide	1694954: Binding affinity to recombinant full length human IRAP expressed in HEK293T cells using Leu-MCA as substrate	ki	0.2005	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-carbamoyl-4-methylpentyl]phosphinic acid	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.2180	uM
benzyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(4-phenylmethoxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.2400	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	1664906: Inhibition of human IRAP soluble domain expressed in HEK293S GnTI(-) cells using Leu-AMC as substrate incubated for 2 hrs by fluorescence based assay	ic50	0.2512	uM
methyl (2S)-2-[[(2R,3S)-2-amino-3-hydroxy-4-[[(2S)-1-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-oxobutyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.2700	uM
benzyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.2800	uM
methyl (2S)-2-[[(3R,4S)-3-amino-4-hydroxy-5-[[(2S)-1-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.3300	uM
[(1R)-1-amino-3-phenylpropyl]-[(2R)-2-carbamoyl-4-methylpentyl]phosphinic acid	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.3440	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(3-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.3600	uM
(2S)-N-hydroxy-3-(4-methoxyphenyl)-2-[4-[[(5-phenylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]propanamide	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.3830	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-5-(3-chlorophenoxy)-2-hydroxypentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.3900	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(4-phenylmethoxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.4600	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2,7-dihydroxyheptanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.5100	uM
(2S)-N-hydroxy-3-(4-phenoxyphenyl)-2-[4-[[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]propanamide	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	0.5600	uM
2-[2-[[[(4S,8S,11S)-11-amino-8-[(4-hydroxyphenyl)methyl]-6,10,14-trioxo-1,5,9-triazacyclotetradecane-4-carbonyl]amino]methyl]phenyl]acetic acid	1694954: Binding affinity to recombinant full length human IRAP expressed in HEK293T cells using Leu-MCA as substrate	ki	0.6744	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(3-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.8200	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-phenylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	0.8300	uM
2-[2-[[[(2S,6S,13S)-13-amino-2-[(4-hydroxyphenyl)methyl]-4,9,14-trioxo-1,5,10-triazacyclotetradecane-6-carbonyl]amino]methyl]phenyl]acetic acid	1694954: Binding affinity to recombinant full length human IRAP expressed in HEK293T cells using Leu-MCA as substrate	ki	0.8870	uM
(4R,8S,11S)-11-amino-N-[[2-(2-amino-2-oxoethyl)phenyl]methyl]-8-[(4-hydroxyphenyl)methyl]-6-oxo-1,2-dithia-5,9-diazacyclotridecane-4-carboxamide	1694954: Binding affinity to recombinant full length human IRAP expressed in HEK293T cells using Leu-MCA as substrate	ki	1.2515	uM
benzyl (2S)-2-[[4-[2-[(2S)-2-aminohexanoyl]hydrazinyl]benzoyl]amino]-3-(1H-indol-3-yl)propanoate	1611468: Competitive inhibition of human recombinant IRAP expressed in baculovirus infected sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ki	1.3000	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-[2-hydroxyethyl(methyl)amino]pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	1.5000	uM
[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	1.7540	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(2-hydroxyethylamino)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	1.9000	uM
benzyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2,5-dihydroxypentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	2.0000	uM
N-phenylbenzenesulfonamide	2066916: Inhibition of IRAP (unknown origin) using L-pNA as substrate	ic50	2.1000	uM
[(2R)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	2066905: Inhibition of IRAP (unknown origin) using L-AMC as substrate	ic50	2.2000	uM
7-amino-4-phenyl-5,7,8,9-tetrahydrobenzo[7]annulen-6-one	2066908: Inhibition of human recombinant IRAP expressed in baculovirus infected Sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ic50	2.4000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(2-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	3.1000	uM
benzyl (2S)-2-[[3-[[(2S)-2-aminohexanoyl]amino]benzoyl]amino]-3-(1H-indol-3-yl)propanoate	1611468: Competitive inhibition of human recombinant IRAP expressed in baculovirus infected sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ki	3.2000	uM
benzyl (2S)-2-[[3-[2-[(2S)-2-aminohexanoyl]hydrazinyl]benzoyl]amino]-3-(1H-indol-3-yl)propanoate	1611468: Competitive inhibition of human recombinant IRAP expressed in baculovirus infected sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ki	3.8000	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(2-hydroxyethylamino)-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	3.9000	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(2-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893373: Inhibition of recombinant IRAP (unknown origin) expressed in HEK293S cells using L-AMC as substrate by flourescence assay	ic50	4.3000	uM
benzyl (2S)-2-[[2-[[(2S)-2-aminohexanoyl]amino]pyridine-4-carbonyl]amino]-3-(1H-indol-3-yl)propanoate	1611468: Competitive inhibition of human recombinant IRAP expressed in baculovirus infected sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ki	4.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases secretion, affects cotreatment, affects expression, increases expression, increases reaction (+2 more)	14
Particulate Matter	increases abundance, increases expression, increases response to substance, decreases expression	6
sodium arsenite	increases expression, decreases expression, increases abundance	5
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects cotreatment, decreases expression	5
Estradiol	affects cotreatment, decreases expression, decreases secretion, increases expression	4
Asbestos, Crocidolite	increases expression, decreases reaction, increases secretion, increases reaction, affects cotreatment	4
3,4,5,3’,4’-pentachlorobiphenyl	increases expression, increases secretion, decreases reaction	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, decreases response to substance	3
Air Pollutants	increases abundance, increases expression, increases response to substance	3
Vehicle Emissions	increases expression, decreases expression, increases abundance	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression, increases methylation	3
2-chloroethyl ethyl sulfide	affects expression, decreases expression, increases secretion	2
Resveratrol	affects cotreatment, increases expression, decreases reaction	2
Air Pollutants, Occupational	increases expression, increases secretion	2
Arsenic	decreases expression, increases abundance, increases expression	2
Indomethacin	decreases expression, decreases reaction, decreases secretion	2
Methotrexate	decreases expression, increases expression	2
Silicon Dioxide	decreases reaction, increases expression, affects reaction, increases secretion	2
Tobacco Smoke Pollution	increases secretion, affects expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Asbestos, Serpentine	increases expression, increases secretion, decreases reaction	2
beta-Naphthoflavone	decreases expression, increases expression	2
Soot	increases abundance, increases expression	2
coagulin-L	decreases reaction, increases expression	1
OTX015	decreases expression	1
Glupearl 19S	increases expression	1
mivebresib	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
7-ketocholesterol	affects cotreatment, increases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4321135	Binding	Inhibition of human IRAP using L-leucine 7-amido-4-methyl coumarin substrate by microplate fluorescence reader based assay	Recent developments in the synthesis and applications of phosphinic peptide analogs. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1CA	Abcam A-431 IL1RN KO 1	Cancer cell line	Female
CVCL_E1FH	Abcam A-431 IL1RN KO 2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients