IL1R1

Summary

IL1R1 (interleukin 1 receptor type 1, HGNC:5993) is a protein-coding gene on chromosome 2q11.2-q12.1, encoding Interleukin-1 receptor type 1 (P14778). Receptor for IL1A, IL1B and IL1RN.

This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12.

Source: NCBI Gene 3554 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chronic recurrent multifocal osteomyelitis 3 (Limited, GenCC)
• GWAS associations: 32
• Clinical variants (ClinVar): 59 total — 2 pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes
• MANE Select transcript: NM_000877

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5993
Approved symbol	IL1R1
Name	interleukin 1 receptor type 1
Location	2q11.2-q12.1
Locus type	gene with protein product
Status	Approved
Aliases	D2S1473, CD121A
Ensembl gene	ENSG00000115594
Ensembl biotype	protein_coding
OMIM	147810
Entrez	3554

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 42 protein_coding, 2 nonsense_mediated_decay

ENST00000409288, ENST00000409329, ENST00000409589, ENST00000409929, ENST00000410023, ENST00000413623, ENST00000422532, ENST00000424272, ENST00000428279, ENST00000430171, ENST00000442590, ENST00000450319, ENST00000452403, ENST00000853658, ENST00000853659, ENST00000853660, ENST00000853661, ENST00000853662, ENST00000853663, ENST00000853664, ENST00000853665, ENST00000853666, ENST00000853667, ENST00000853668, ENST00000853669, ENST00000853670, ENST00000853671, ENST00000853672, ENST00000853673, ENST00000853674, ENST00000853675, ENST00000959752, ENST00000959753, ENST00000959754, ENST00000959755, ENST00000959756, ENST00000959757, ENST00000959758, ENST00000959759, ENST00000959760, ENST00000959761, ENST00000959762, ENST00000959763, ENST00000959764

RefSeq mRNA: 10 — MANE Select: NM_000877 NM_000877, NM_001288706, NM_001320978, NM_001320980, NM_001320981, NM_001320982, NM_001320983, NM_001320984, NM_001320985, NM_001320986

CCDS: CCDS2055, CCDS74547

Canonical transcript exons

ENST00000410023 — 12 exons

Exon	Start	End
ENSE00000804348	102157719	102157785
ENSE00000804349	102176353	102179874
ENSE00001588344	102153941	102154017
ENSE00003464529	102172687	102172838
ENSE00003496865	102175478	102175645
ENSE00003502230	102168598	102168663
ENSE00003546665	102171801	102171918
ENSE00003620243	102165115	102165304
ENSE00003621191	102164774	102165008
ENSE00003672072	102174587	102174730
ENSE00003675269	102166113	102166281
ENSE00003846337	102142746	102143020

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.0503 / max 461.9363, expressed in 1447 samples.

FANTOM5 promoters (24 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21688	16.3460	1353
21673	4.5361	659
21672	1.0512	398
21674	0.8304	336
21682	0.7642	274
21691	0.5066	277
21683	0.4007	178
21666	0.3694	164
21671	0.3602	192
21690	0.2765	168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.72	gold quality
tibia	UBERON:0000979	99.56	gold quality
pericardium	UBERON:0002407	99.35	gold quality
corpus epididymis	UBERON:0004359	99.21	gold quality
decidua	UBERON:0002450	99.18	gold quality
caput epididymis	UBERON:0004358	98.99	gold quality
urethra	UBERON:0000057	98.62	gold quality
vena cava	UBERON:0004087	98.52	gold quality
visceral pleura	UBERON:0002401	98.49	gold quality
placenta	UBERON:0001987	98.40	gold quality
pleura	UBERON:0000977	98.37	gold quality
parietal pleura	UBERON:0002400	98.31	gold quality
germinal epithelium of ovary	UBERON:0001304	98.28	gold quality
lower lobe of lung	UBERON:0008949	98.27	gold quality
seminal vesicle	UBERON:0000998	98.04	gold quality
colonic epithelium	UBERON:0000397	97.91	gold quality
periodontal ligament	UBERON:0008266	97.90	gold quality
skin of hip	UBERON:0001554	97.67	gold quality
synovial joint	UBERON:0002217	97.62	gold quality
cartilage tissue	UBERON:0002418	97.61	gold quality
superficial temporal artery	UBERON:0001614	97.57	gold quality
endometrium	UBERON:0001295	97.56	gold quality
peritoneum	UBERON:0002358	97.51	gold quality
omental fat pad	UBERON:0010414	97.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.36	gold quality
layer of synovial tissue	UBERON:0007616	97.18	gold quality
lung	UBERON:0002048	97.17	gold quality
gall bladder	UBERON:0002110	97.17	gold quality
upper leg skin	UBERON:0004262	97.17	gold quality
upper lobe of lung	UBERON:0008948	97.17	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	623.67
E-HCAD-30	yes	207.48
E-MTAB-10042	yes	108.67
E-CURD-119	yes	17.26
E-HCAD-9	yes	14.93
E-MTAB-6678	yes	9.71
E-GEOD-81547	yes	9.05
E-CURD-122	yes	8.78
E-MTAB-9067	yes	6.27
E-GEOD-70580	no	1023.64
E-MTAB-10137	no	7.38
E-CURD-112	no	2.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CTNNB1, NFKB, RORC, STAT1, STAT6

miRNA regulators (miRDB)

158 targeting IL1R1, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• Heparins (unfractionated heparin, UFH and low molecular weight heparin certoparin) had no effect on the release of IL-1ra, IL-10, and IL-12p40 from neutrophils or peripheral blood mononuclear cells. (PMID:11820460)
• Carriage of IL1beta and IL1RN*2, together with non-carriage of TNF2 is associated with increased susceptibility, but not with a prognosis of IgAN. (PMID:11849463)
• Carriage of ILRN*2 alleles influences disease severity rather than susceptibility. (PMID:12136897)
• IL-1 receptor has a role in the pathway linking static compression to reduced proteoglycan synthesis (PMID:12729621)
• A decrease in interleukin-1 receptor antagonist expression in the prefrontal cortex of schizophrenic patients. (PMID:12804791)
• high allele frequency of the IL1RN*2 allele may affect disease susceptibility in childhood nephrotic syndrome (PMID:14758530)
• IL-1RA gene polymorphism is not responsible for specific clinical characteristics in RA and SLE but that IL-1RN*2 is relevant in the susceptibility to RA. (PMID:14872281)
• There is an association between polymorphisms of the promoter region -511C/T of IL-1B and IL-1RN intron 2 and chronic hepatitis B virus infection (PMID:15188516)
• Sixteen SNPs were identified through a 9643 bp sequencing of IL-1R1 gene. Four were in 5’ flank region, four in intron region, one in coding region, and seven in 3’ untranslated region. (PMID:15300624)
• Data show that Exip, but not p38alpha, binds to Toll interacting protein, which is involved in interleukin-1 (IL-1) signaling pathway, and impaired NF-kappaB activity. (PMID:15388348)
• the dysregulation of IL-1/IL-1-R system relates to immunological dysfunction in endometriosis (PMID:15472211)
• SIGIRR inhibits IL-1R and TLR4-mediated signaling through different mechanisms (PMID:15866876)
• Our findings indicate that the VDR FokI polymorphism and several VDR and IL-1-R1 haplotypes are associated with susceptibility to T1DM in the Dalmatian population. (PMID:16258158)
• data describe percentage of bone marrow cells expressing receptors for interleukin-1, platelet-derived growth factor, fibroblast growth factor, transforming growth factor-beta, epidermal growth factor and c-Fos and c-Myc in untreated lung & breast cancer (PMID:16305343)
• Rac1 facilitated the recruitment of Nox2 into the endosomal compartment and subsequent redox-dependent recruitment of TRAF6 to the MyD88/IL-1R1 complex. (PMID:16354686)
• icIL-1ra1 does not act at an intracellular level to alter IL-1 mediated signalling, and is effective in inhibiting IL-1 responses only when released in an ATP-dependent and cell type specific manner (PMID:16564702)
• Distributions of single-base polymorphisms of the human IL-1RI gene were evaluated and a C–>A transition in exon 1C showed protective effect against endometriosis in heterozygotes. (PMID:16911713)
• Our study showed an imbalance in the expression of IL1R1 and IL1R2 in eutopic, and particularly in ectopic, endometrial tissues of women with endometriosis (PMID:17324958)
• Conformational stability of rhIL1ra was monitored by equilibrium urea denaturation, and thermodynamic parameters of unfolding; conformational stability, monitored using the Cm value, has an effect on oxidation rates of buried methionines (PMID:17480058)
• Abnormal interleukin 1 receptor types I and II gene expression in eutopic and ectopic endometrial tissues of women with endometriosis. (PMID:17517439)
• rheumatic heart disease cases showed a significantly higher frequency of homozygous genotypes of IL-1Ra A1/A1. Cases with mitral valve disease showed higher frequencies of genotype IL-1Ra(VNTR) A1/A1. (PMID:17607501)
• This study shows an increase in gene and protein production for the IL-1 receptor type I in degenerate intervertebral discs. (PMID:17688691)
• results showed that there was a gender difference in IL-1Ra gene polymorphism expressed by a higher incidence of IL1RN*1/IL1RN*1 homozygotes and a lower occurrence of IL1RN*1/IL1RN*2 heterozygotes in men compared with women (PMID:18052726)
• The expression of the IL-1 receptor, a known regulator of SREBP-2, was also elevated after exercise. (PMID:18321953)
• polymorphism is not associated with the presence of pulmonary aspergillosis infection; but in combination with IL1a and IL1b genotypes may predict disease susceptibility (PMID:18484169)
• Mild or intensive immunoreactivity for IL-1RI was observed in the epithelial cells in all cases, and in the endothelial cells and fibroblasts in five cases of keratocystic odontogenic tumors. (PMID:18624935)
• IL-6 and IL-1Ra polymorphisms can be considered genetic markers for bronchial asthma susceptibility and/or severity among Egyptian children. (PMID:18810365)
• TRAF6 and interleukin receptor-associated kinase 2 are novel binding partners for PS1, and IL-1R1 is a new substrate for presenilin-dependent gamma-secretase cleavage (PMID:18996842)
• Long-term, but not short-term memory is impaired in a transgenic mouse strain overexpressing human soluble interleukin-1 receptor antagonist (IL-1ra) in the brain. (PMID:19211154)
• These results indicate that TRAF6-mediated ubiquitination of IL-1R1 has a decisive role in IL-1R1 signalling and propose a molecular mechanism whereby TRAF6 promotes ubiquitination and RIP of IL-1R1 through its ubiquitin ligase activity. (PMID:19232518)
• IL-1ra was expressed within the length of the human fallopian tube only in menstrual cycle secretory phase and in the intraauterine pregnancies samples (PMID:19428986)
• This study indicated that statistically significant higher protein and mRNA levels of the il1r in frontal corte in bipolar disorder. (PMID:19488045)
• This the first study to show a positive correlation between polymorphisms in the IL-1alpha and IL-1RA genes and susceptibility to Graves’ ophthalmopathy. (PMID:19702713)
• DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation. (PMID:19716405)
• Data show that Nox2 and IL-1R1 localize to plasma membrane lipid rafts in the unstimulated state and that IL-1beta signals caveolin-1-dependent endocytosis of both proteins into the redoxosome. (PMID:19801678)
• Data show that activation of TLR2 in purified human beta-cells and islets stimulated the expression of proinflammatory factors, and IL-1RI activity increased the TLR2 response in human islets. (PMID:19819943)
• Data suggest that in the Brazilian population, the polymorphism of the IL-1ra gene is a relevant factor for rheumatic heart disease severity. (PMID:19822442)
• Data suggest that TILRR is an IL-1RI co-receptor, which associates with the signaling receptor complex to enhance recruitment of MyD88 and control Ras-dependent amplification of NF-kappaB and inflammatory responses. (PMID:19940113)
• Data demonstrate that PKC-alpha is induced by several MyD88-dependent TLR/IL-1R ligands and regulates cytokine expression in human and murine DC. (PMID:19950169)
• Human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15. (PMID:19965648)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il1r1	ENSMUSG00000026072
rattus_norvegicus	Il1r1	ENSRNOG00000014504

Paralogs (10): LAG3 (ENSG00000089692), IL1R2 (ENSG00000115590), IL1RL2 (ENSG00000115598), IL1RL1 (ENSG00000115602), IL18R1 (ENSG00000115604), IL18RAP (ENSG00000115607), IL1RAPL1 (ENSG00000169306), SIGIRR (ENSG00000185187), IL1RAPL2 (ENSG00000189108), IL1RAP (ENSG00000196083)

Protein

Protein identifiers

Interleukin-1 receptor type 1 — P14778 (reviewed: P14778)

Alternative names: CD121 antigen-like family member A, Interleukin-1 receptor alpha, Interleukin-1 receptor type I, p80

All UniProt accessions (11): P14778, B8ZZ73, B8ZZW4, B9A040, C9J3W8, C9J686, C9JQ36, C9JW84, C9JWB2, F8WF92, H7BZM5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex. Involved in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells.

Subunit / interactions. The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Interacts with PIK3R1. Interacts with IL1A.

Subcellular location. Membrane. Cell membrane. Secreted.

Tissue specificity. Expressed in T-helper cell subsets. Preferentially expressed in T-helper 1 (Th1) cells.

Post-translational modifications. A soluble form (sIL1R1) is probably produced by proteolytic cleavage at the cell surface (shedding). Rapidly phosphorylated on Tyr-496 in response to IL-1, which creates a SH2 binding site for the PI 3-kinase regulatory subunit PIK3R1.

Disease relevance. Chronic recurrent multifocal osteomyelitis 3 (CRMO3) [MIM:259680] An autosomal dominant autoinflammatory bone disease characterized by early-childhood onset of bone pain and arthritis caused by sterile osteomyelitis. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.

Similarity. Belongs to the interleukin-1 receptor family.

RefSeq proteins (10): NP_000868, NP_001275635, NP_001307907, NP_001307909, NP_001307910, NP_001307911, NP_001307912, NP_001307913, NP_001307914, NP_001307915 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR003599	Ig_sub	Domain
IPR004074	IL-1_rcpt_I/II-typ	Family
IPR004076	IL-1_rcpt_I-typ	Family
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015621	IL-1_rcpt_fam	Family
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR041416	IL-1RAcP-like_ig	Domain

Pfam: PF01582, PF13895, PF18452

Catalyzed reactions (Rhea), 1 shown:

• NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+) (RHEA:16301)

UniProt features (68 total): strand 27, helix 7, glycosylation site 6, disulfide bond 5, mutagenesis site 5, domain 4, sequence variant 3, chain 2, topological domain 2, signal peptide 1, region of interest 1, compositionally biased region 1, active site 1, modified residue 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4GAF	X-RAY DIFFRACTION	2.15
1ITB	X-RAY DIFFRACTION	2.5
1IRA	X-RAY DIFFRACTION	2.7
1G0Y	X-RAY DIFFRACTION	3
4DEP	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14778-F1	84.30	0.51

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): 470

Post-translational modifications (1): 496

Disulfide bonds (5): 23–104, 44–96, 121–164, 142–196, 248–312

Glycosylation sites (6): 100, 193, 233, 249, 263, 297

Mutagenesis-validated functional residues (5):

Position	Phenotype
131	severely decreased interaction with il1rn.
131	no effect on interaction with il1rn.
369	reduces nf-kappa-b activation.
428	reduces nf-kappa-b activation and receptor-associated kinase activation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6783783	Interleukin-10 signaling
R-HSA-9020702	Interleukin-1 signaling
R-HSA-9679191	Potential therapeutics for SARS

MSigDB gene sets: 522 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_545, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, HOFMANN_CELL_LYMPHOMA_UP, GOBP_MACROPHAGE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP

GO Biological Process (16): inflammatory response (GO:0006954), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), positive regulation of platelet-derived growth factor receptor signaling pathway (GO:0010641), smooth muscle adaptation (GO:0014805), positive regulation of type II interferon production (GO:0032729), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of inflammatory response (GO:0050727), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), interleukin-1-mediated signaling pathway (GO:0070498), response to interleukin-1 (GO:0070555), positive regulation of neutrophil extravasation (GO:2000391), positive regulation of T-helper 1 cell cytokine production (GO:2000556), positive regulation of interleukin-1-mediated signaling pathway (GO:2000661), signal transduction (GO:0007165), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (10): protease binding (GO:0002020), transmembrane signaling receptor activity (GO:0004888), interleukin-1 receptor activity (GO:0004908), interleukin-1, type I, activating receptor activity (GO:0004909), platelet-derived growth factor receptor binding (GO:0005161), interleukin-1 binding (GO:0019966), NAD+ nucleosidase activity, cyclic ADP-ribose generating (GO:0061809), cytokine receptor activity (GO:0004896), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Interleukins	1
Interleukin-1 family signaling	1
SARS-CoV Infections	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of intracellular signal transduction	2
cytokine-mediated signaling pathway	2
interleukin-1-mediated signaling pathway	2
cytokine binding	2
defense response	1
immune system process	1
response to stimulus	1
signal transduction	1
positive regulation of signal transduction	1
regulation of platelet-derived growth factor receptor signaling pathway	1
platelet-derived growth factor receptor signaling pathway	1
muscle adaptation	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
cellular response to interleukin-1	1
response to cytokine	1
positive regulation of cellular extravasation	1
neutrophil extravasation	1
positive regulation of neutrophil migration	1
regulation of neutrophil extravasation	1
positive regulation of T cell cytokine production	1
positive regulation of T-helper 1 type immune response	1
T-helper 1 cell cytokine production	1
regulation of T-helper 1 cell cytokine production	1
positive regulation of cytokine-mediated signaling pathway	1
regulation of interleukin-1-mediated signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1

Protein interactions and networks

STRING

2743 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL1R1	IL1A	P01583	999
IL1R1	IL1B	P01584	999
IL1R1	MYD88	P78397	998
IL1R1	IL1RN	P18510	997
IL1R1	IL6	P05231	997
IL1R1	IRAK1	P51617	996
IL1R1	TNF	P01375	996
IL1R1	IL1RAP	Q9NPH3	988
IL1R1	IL33	O95760	988
IL1R1	TRAF6	Q9Y4K3	987
IL1R1	IL1R2	P27930	971
IL1R1	IL18	Q14116	965
IL1R1	IL1RL2	Q9HB29	963
IL1R1	IRAK4	Q9NWZ3	945
IL1R1	TLR4	O00206	936

IntAct

17 interactions, top by confidence:

A	B	Type	Score
IL1RAP	IL1B	psi-mi:“MI:0915”(physical association)	0.760
IL1RN	IL1R1	psi-mi:“MI:0407”(direct interaction)	0.610
IL1R1	IL1RN	psi-mi:“MI:0915”(physical association)	0.610
IL1R1	TRAF6	psi-mi:“MI:0915”(physical association)	0.500
IL1B	IL1R1	psi-mi:“MI:0407”(direct interaction)	0.440
IL1R1	PDGFRB	psi-mi:“MI:0915”(physical association)	0.400
IL1R1	MYH10	psi-mi:“MI:0915”(physical association)	0.400
IL1R1	MATR3	psi-mi:“MI:0915”(physical association)	0.400
IL1R1	TICAM2	psi-mi:“MI:0915”(physical association)	0.400
IL1R1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
VPS39	IL1R1	psi-mi:“MI:0914”(association)	0.350
IL1R1	MAP3K14	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): ATP2A3 (Affinity Capture-MS), ICK (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), SIGIRR (Affinity Capture-Western), IL1R1 (Affinity Capture-Western), IL1R1 (Affinity Capture-Western), IL1R1 (Affinity Capture-Western), IL1R1 (Affinity Capture-Western), IL1R1 (Affinity Capture-Western), IL1RAP (Affinity Capture-Western), IL1R1 (Affinity Capture-Western), MYH10 (Proximity Label-MS)

ESM2 similar proteins: A3KPA0, A5A6L6, A5D7C3, O60487, O70255, O88792, P01865, P01903, P01904, P01910, P04224, P04228, P14434, P14439, P14778, P15980, P22646, P23150, P53788, P57087, P59822, P97952, Q00954, Q02955, Q07699, Q17QN4, Q1WIM2, Q28740, Q2WGK2, Q30631, Q3TEW6, Q3V3F6, Q4PPC4, Q5EAB0, Q5R804, Q61730, Q62929, Q63621, Q66KX2, Q68FQ2

Diamond homologs: P13504, P14778, P27930, P43303, Q02955, Q29612, Q62929, Q9ERS7, Q9HB29, P27931, Q9NP60, O57261, P25212, Q61790, A0A7H0DNG1, Q04523, Q9ERS6, Q6IA17, Q9JLZ8, Q4V892

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
IL1R1	“up-regulates activity”	IRAK1
IL1R1	up-regulates	Inflammation
IL1B	“up-regulates activity”	IL1R1	binding
IL1R1	“up-regulates activity”	NfKb-p65/p50
IL1R1	“up-regulates activity”	MAPK8	phosphorylation
IL1R1	“up-regulates activity”	MAPK9	phosphorylation
IL1R1	“up-regulates activity”	MAPK10	phosphorylation
IL1R1	“up-regulates activity”	IL1RAP	binding
IL1RN	“down-regulates activity”	IL1R1	binding
IL1R1	“up-regulates activity”	JNK	phosphorylation
IRAK2	“up-regulates activity”	IL1R1	binding
TRAF6	“down-regulates quantity by destabilization”	IL1R1	ubiquitination
IL1A	“up-regulates activity”	IL1R1	binding
IL1B	up-regulates	IL1R1	binding
IL1R1	“up-regulates activity”	MYD88	binding
IL1RAP	up-regulates	IL1R1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2574622	NM_000877.4(IL1R1):c.391A>G (p.Lys131Glu)	Pathogenic
442998	GRCh37/hg19 2p25.3-q37.3(chr2:12771-242783384)	Pathogenic

SpliceAI

2502 predictions. Top by Δscore:

Variant	Effect	Δscore
2:102154025:GGC:G	donor_gain	1.0000
2:102157709:A:AG	acceptor_gain	1.0000
2:102157710:T:G	acceptor_gain	1.0000
2:102157791:T:G	donor_gain	1.0000
2:102168592:TTTCA:T	acceptor_loss	1.0000
2:102168593:TTCA:T	acceptor_loss	1.0000
2:102168595:CA:C	acceptor_loss	1.0000
2:102168596:A:AG	acceptor_gain	1.0000
2:102168596:AGAG:A	acceptor_gain	1.0000
2:102168597:G:GG	acceptor_gain	1.0000
2:102168597:G:GT	acceptor_loss	1.0000
2:102168597:GA:G	acceptor_gain	1.0000
2:102168597:GAGG:G	acceptor_gain	1.0000
2:102168597:GAGGA:G	acceptor_gain	1.0000
2:102168651:G:GT	donor_gain	1.0000
2:102168651:G:T	donor_gain	1.0000
2:102168662:GG:G	donor_gain	1.0000
2:102168663:GG:G	donor_gain	1.0000
2:102168664:G:GG	donor_gain	1.0000
2:102171797:GCA:G	acceptor_loss	1.0000
2:102171799:A:AG	acceptor_gain	1.0000
2:102171799:AG:A	acceptor_gain	1.0000
2:102171800:G:GA	acceptor_gain	1.0000
2:102171800:GG:G	acceptor_gain	1.0000
2:102171800:GGA:G	acceptor_gain	1.0000
2:102171800:GGAT:G	acceptor_gain	1.0000
2:102171800:GGATC:G	acceptor_gain	1.0000
2:102171916:CAG:C	donor_gain	1.0000
2:102171917:AG:A	donor_gain	1.0000
2:102171918:GG:G	donor_gain	1.0000

AlphaMissense

3761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:102165298:G:C	W160C	0.997
2:102165298:G:T	W160C	0.997
2:102171821:T:A	C248S	0.997
2:102171822:G:C	C248S	0.997
2:102171859:G:C	W260C	0.997
2:102171859:G:T	W260C	0.997
2:102172781:T:A	C312S	0.995
2:102172782:G:C	C312S	0.995
2:102165296:T:A	W160R	0.994
2:102165296:T:C	W160R	0.994
2:102171822:G:A	C248Y	0.994
2:102172776:T:G	F310C	0.994
2:102165242:T:A	C142S	0.993
2:102165242:T:C	C142R	0.993
2:102165243:G:C	C142S	0.993
2:102166258:G:C	R211P	0.993
2:102172783:T:G	C312W	0.993
2:102171821:T:C	C248R	0.992
2:102172776:T:C	F310S	0.992
2:102166212:T:A	C196S	0.991
2:102166213:G:C	C196S	0.991
2:102171857:T:A	W260R	0.991
2:102171857:T:C	W260R	0.991
2:102164881:T:A	W57R	0.990
2:102164881:T:C	W57R	0.990
2:102164883:G:C	W57C	0.990
2:102164883:G:T	W57C	0.990
2:102171823:T:G	C248W	0.990
2:102172781:T:C	C312R	0.990
2:102172782:G:A	C312Y	0.990

dbSNP variants (sampled 300 via entrez): RS1000003935 (2:102142706 C>T), RS1000018088 (2:102105185 T>C), RS1000034289 (2:102123135 G>A), RS1000063578 (2:102105762 C>T), RS1000091763 (2:102128851 A>G), RS1000104819 (2:102099845 G>A,T), RS1000158004 (2:102136570 GT>G), RS1000177617 (2:102137101 A>C), RS1000184666 (2:102151221 G>A), RS1000261322 (2:102148751 G>A,C), RS1000278122 (2:102130934 A>G), RS1000278949 (2:102094938 G>T), RS1000307503 (2:102098235 G>A), RS1000325084 (2:102135250 G>A), RS1000335987 (2:102089302 T>C)

Disease associations

OMIM: gene MIM:147810 | disease phenotypes: MIM:259680

GenCC curated gene-disease

Disease	Classification	Inheritance
chronic recurrent multifocal osteomyelitis 3	Limited	Autosomal dominant

Mondo (1): chronic recurrent multifocal osteomyelitis 3 (MONDO:0958177)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001945	Fever
HP:0002653	Bone pain
HP:0002754	Osteomyelitis
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0100847	Palmoplantar pustulosis

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST001508_6	Asthma	6.000000e-08
GCST001725_46	Inflammatory bowel disease	3.000000e-20
GCST002147_11	Fibrinogen	3.000000e-08
GCST002166_2	Serum protein levels (sST2)	6.000000e-20
GCST002690_3	Very long-chain saturated fatty acid levels (fatty acid 20:0)	8.000000e-06
GCST003129_29	Primary biliary cholangitis	5.000000e-09
GCST003194_9	Fibrinogen levels	3.000000e-10
GCST004121_20	Fibrinogen levels	6.000000e-10
GCST004122_14	Fibrinogen levels	6.000000e-10
GCST004131_93	Inflammatory bowel disease	5.000000e-11
GCST004132_63	Crohn’s disease	6.000000e-11
GCST005529_26	Ankylosing spondylitis	4.000000e-06
GCST005529_65	Ankylosing spondylitis	1.000000e-06
GCST005529_8	Ankylosing spondylitis	1.000000e-07
GCST005537_162	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-09
GCST005987_27	Albumin-globulin ratio	2.000000e-09
GCST006104_7	Interleukin-1-receptor antagonist levels	1.000000e-06
GCST006585_1713	Blood protein levels	3.000000e-10
GCST007362_7	Acute anterior uveitis (with or without ankylosing spondylitis)	2.000000e-06
GCST007562_4	Asthma	7.000000e-18
GCST007563_2	Allergic disease (asthma, hay fever or eczema)	4.000000e-24
GCST007564_34	Asthma or allergic disease (pleiotropy)	2.000000e-27
GCST007614_38	C-reactive protein levels	7.000000e-11
GCST007797_21	Asthma onset (childhood vs adult)	3.000000e-08
GCST007798_17	Asthma	1.000000e-19
GCST007800_19	Asthma (childhood onset)	5.000000e-37
GCST008916_108	Asthma	1.000000e-22
GCST008916_29	Asthma	2.000000e-60
GCST008916_72	Asthma	2.000000e-08
GCST009798_51	Asthma	8.000000e-43

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0005128	albumin:globulin ratio measurement
EFO:0004754	interleukin 1 receptor antagonist measurement
EFO:0004458	C-reactive protein measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1959 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Immunoglobulin-like family of IL-1 receptors

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.50	Kd	0.316	nM	CHEMBL1626304
6.14	IC50	720	nM	CHEMBL4213787

PubChem BioAssay actives

2 with measured affinity, of 11 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
2-(1,2-diphenylindol-3-yl)ethanamine	1924939: Inhibition of human IL1-R1 assessed as dissociation constant incubated for 5 mins by SPR analysis	kd	0.0003	uM
2-(2,4-dichlorophenyl)-N’-(pyridine-2-carbonyl)-1,3-thiazole-4-carbohydrazide	1381057: Inhibition of IL1R in TLR null HEK-blue cells assessed as decrease in IL-1beta-stimulated NF-kappaB activation-mediated SEAP production after 24 hrs by Quanti-blue-based assay	ic50	0.7200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	7
sodium arsenite	decreases reaction, increases expression, affects expression, decreases expression	6
Estradiol	affects cotreatment, increases expression, decreases expression, decreases reaction	5
Acetaminophen	decreases expression, increases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance, affects expression	3
Cannabidiol	decreases expression, decreases reaction	3
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance	3
Quercetin	decreases expression, increases expression	3
Silver	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
Triclosan	affects cotreatment, increases expression, decreases expression	3
Cyclosporine	decreases expression	3
sulforaphane	decreases expression, increases expression	2
perfluorooctanoic acid	decreases expression, affects cotreatment, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cannabinoids	affects methylation, increases abundance, decreases expression, decreases reaction	2
Cisplatin	affects cotreatment, decreases expression, affects response to substance	2
Formaldehyde	decreases expression, increases expression	2
Ozone	affects expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Dinoprostone	increases expression, increases activity	2
bisphenol F	increases expression, affects cotreatment	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3766039	Binding	Inhibition of IL-1 receptor (unknown origin) at 10 uM	Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9831	293-IL-1RI	Transformed cell line	Female
CVCL_D7S3	Ubigene A-549 IL1R1 KO	Cancer cell line	Male
CVCL_D8N4	Ubigene HCT 116 IL1R1 KO	Cancer cell line	Male
CVCL_E0F0	Ubigene HeLa IL1R1 KO	Cancer cell line	Female
CVCL_UF33	HEK-Blue IL-18	Transformed cell line	Female
CVCL_UF59	HEK-Blue IL-33	Transformed cell line	Female

Clinical trials (associated diseases)

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