IL18RAP

Summary

IL18RAP (interleukin 18 receptor accessory protein, HGNC:5989) is a protein-coding gene on chromosome 2q12.1, encoding Interleukin-18 receptor accessory protein (O95256). Within the IL18 receptor complex, does not mediate IL18-binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation.

The protein encoded by this gene is an accessory subunit of the heterodimeric receptor for interleukin 18 (IL18), a proinflammatory cytokine involved in inducing cell-mediated immunity. This protein enhances the IL18-binding activity of the IL18 receptor and plays a role in signaling by IL18. Mutations in this gene are associated with Crohn’s disease and inflammatory bowel disease, and susceptibility to celiac disease and leprosy. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 8807 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 82 total
• Druggable target: yes
• MANE Select transcript: NM_001393487

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5989
Approved symbol	IL18RAP
Name	interleukin 18 receptor accessory protein
Location	2q12.1
Locus type	gene with protein product
Status	Approved
Aliases	AcPL, CD218b
Ensembl gene	ENSG00000115607
Ensembl biotype	protein_coding
OMIM	604509
Entrez	8807

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000264260, ENST00000409369, ENST00000450855, ENST00000497795, ENST00000687160, ENST00000863555

RefSeq mRNA: 5 — MANE Select: NM_001393487 NM_001393486, NM_001393487, NM_001393488, NM_001393489, NM_003853

CCDS: CCDS2061, CCDS92824

Canonical transcript exons

ENST00000687160 — 10 exons

Exon	Start	End
ENSE00000772465	102423811	102424135
ENSE00000772467	102437212	102437362
ENSE00000772468	102441312	102441377
ENSE00000772469	102443200	102443323
ENSE00000772470	102445189	102445340
ENSE00000772471	102447070	102447207
ENSE00000772472	102450848	102451021
ENSE00000804371	102451766	102452565
ENSE00003480368	102424231	102424414
ENSE00003927468	102423160	102423347

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 97.14.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4356 / max 833.1891, expressed in 186 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21743	0.9189	84
21734	0.5657	94
21733	0.5212	103
21732	0.2899	72
21744	0.0444	9
21741	0.0430	8
21742	0.0334	9
202325	0.0191	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.14	gold quality
blood	UBERON:0000178	95.64	gold quality
bone marrow	UBERON:0002371	92.37	gold quality
spleen	UBERON:0002106	90.29	gold quality
trabecular bone tissue	UBERON:0002483	89.42	gold quality
right lung	UBERON:0002167	87.13	gold quality
bone marrow cell	CL:0002092	86.55	gold quality
upper lobe of left lung	UBERON:0008952	83.34	gold quality
upper lobe of lung	UBERON:0008948	82.06	gold quality
periodontal ligament	UBERON:0008266	82.04	gold quality
vermiform appendix	UBERON:0001154	79.56	gold quality
left uterine tube	UBERON:0001303	78.85	gold quality
omental fat pad	UBERON:0010414	76.69	gold quality
peritoneum	UBERON:0002358	76.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.18	gold quality
amniotic fluid	UBERON:0000173	75.99	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.96	gold quality
gall bladder	UBERON:0002110	73.29	gold quality
small intestine	UBERON:0002108	73.28	gold quality
caecum	UBERON:0001153	72.89	gold quality
leukocyte	CL:0000738	72.65	gold quality
lung	UBERON:0002048	72.54	gold quality
palpebral conjunctiva	UBERON:0001812	72.01	gold quality
right lobe of liver	UBERON:0001114	71.45	gold quality
mononuclear cell	CL:0000842	71.12	gold quality
lymph node	UBERON:0000029	70.58	gold quality
monocyte	CL:0000576	70.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.33	gold quality
rectum	UBERON:0001052	69.88	gold quality
body of stomach	UBERON:0001161	69.26	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.71
E-CURD-89	no	553.16
E-MTAB-4850	no	455.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting IL18RAP, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3912-5P	99.95	66.11	925
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-379-5P	97.52	67.81	485
HSA-MIR-3529-5P	97.12	67.06	440
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-601	95.98	67.59	421
HSA-MIR-4515	95.70	65.73	716

Literature-anchored findings (GeneRIF, showing 26)

• IL-18, IL-18 receptor alpha, and CD48 complex formation via glycosylphosphatidylinositol anchor glycan triggers binding to IL-18 receptor beta, and thereby induces intracellular signal transduction and IFN-gamma production. (PMID:15760905)
• Truncated forms of IL-18RAP may be involved in the complex mechanism of IL-18 activity regulation. (PMID:17897836)
• Variations in IL18RAP is associated with celiac disease (PMID:18311140)
• CARD9 and IL18RAP are IBD loci important in innate immunity in the predisposition to both CD and UC. (PMID:18439550)
• study provides suggestive evidence for associations of SNPs in the IL1RL1 gene and adjacently located family members IL18R1 and IL18RAP with asthma and atopy in 2 independent Dutch asthma populations (PMID:18774397)
• IL18RAP is a novel predisposing gene for coeliac disease. (PMID:19103669)
• Our analysis suggests that the variability of IL18RAP genes is unlikely to contribute to modulate the risk of cardiovascular disease (PMID:19473509)
• Investigated the regions 2q12 (IL18RAP) and 3p21 (CCR3)in regards to celiac disease risk in the Spanish population.Two SNPs, rs917997 (2q12) and rs6441961 (3p21), were genotyped; Assoc’n was found w/rs6441961, a non-sign. result was obtained for rs917997. (PMID:19542083)
• The mechanism of the impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis involves a defect in IL-18Rbeta phosphorylation. (PMID:19714583)
• Data suggest that IL-18RAP and IL-18R1 single-nucleotide polymorphisms identify African-American infants at risk for bronchopulmonary dysplasia. (PMID:22289858)
• Data indicate that MyD88 works together with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner. (PMID:22685567)
• The SNP modified IL18RAP surface protein expression by NK cells. (PMID:23891168)
• results demonstrate clear functional consequences of the rs917997 risk polymorphism; this polymorphism leads to a loss-of-function through decreased IL-18RAP, IL-18R1, and IL-1R1 protein expression, which impairs autocrine IL-18 and IL-1 signaling (PMID:24842757)
• This meta-analysis provides robust estimates that IL18RAP rs917997 and chemokine (C-C motif) receptor 3 rs6441961 are potential risk factors for celiac disease in European populations. (PMID:26289103)
• These findings suggested that IL-18RAP rs917997, IL-32 rs2015620, IL-22 rs1179251, and interactions between these polymorphisms and H. pylori infection were associated with risks of gastric lesions (PMID:26358252)
• some SNPs of ST2-IL18R1-IL18RAP gene cluster might increase the risk of susceptibility of Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in Chinese Han population. (PMID:26566691)
• An association of IL18RAP single nucleotide polymorphism rs2058660 with Behcet’s disease, but not Vogt-Koyanagi-Harada disease in Han Chinese. (PMID:27775096)
• Polymorphisms in IL18RAP influence susceptibility to obesity. We demonstrated that the A allele in rs7559479 increases MIR136 binding, which regulates IL-18 system activity. (PMID:29146643)
• There was no association between IL18RAP gene polymorphisms (rs1420106 and rs917997) with the risk of spondylotic myelopathy in Indian population. (PMID:31126849)
• IL18RAP polymorphisms and its plasma levels in patients with Lumbar disc degeneration. (PMID:31147177)
• Investigation of genetically regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response. (PMID:32732242)
• IL18-family Genes Polymorphism Is Associated with the Risk of Myocardial Infarction and IL18 Concentration in Patients with Coronary Artery Disease. (PMID:33522333)
• Integrating disease and drug-related phenotypes for improved identification of pharmacogenomic variants. (PMID:33769074)
• A novel anti-human IL-1R7 antibody reduces IL-18-mediated inflammatory signaling. (PMID:33823154)
• Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3’UTR protect against ALS. (PMID:35361972)
• Prognostic and immunological roles of IL18RAP in human cancers. (PMID:37698530)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il18rap	ENSMUSG00000026068
rattus_norvegicus	Il18rap	ENSRNOG00000054218

Paralogs (10): LAG3 (ENSG00000089692), IL1R2 (ENSG00000115590), IL1R1 (ENSG00000115594), IL1RL2 (ENSG00000115598), IL1RL1 (ENSG00000115602), IL18R1 (ENSG00000115604), IL1RAPL1 (ENSG00000169306), SIGIRR (ENSG00000185187), IL1RAPL2 (ENSG00000189108), IL1RAP (ENSG00000196083)

Protein

Protein identifiers

Interleukin-18 receptor accessory protein — O95256 (reviewed: O95256)

Alternative names: Accessory protein-like, CD218 antigen-like family member B, CDw218b, IL-1R accessory protein-like, Interleukin-1 receptor 7, Interleukin-18 receptor accessory protein-like, Interleukin-18 receptor beta

All UniProt accessions (2): O95256, C9JLE2

UniProt curated annotations — full annotation on UniProt →

Function. Within the IL18 receptor complex, does not mediate IL18-binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation. May play a role in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells.

Subunit / interactions. Forms a ternary complex with IL18 and IL18R1. Within this complex, IL18R1 is involved in ligand-binding and IL18RAP in signaling leading to NF-kappa-B and JNK activation.

Subcellular location. Cell membrane.

Tissue specificity. Detected in adrenal gland, bone marrow, brain, fetal brain, fetal liver, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, prostate, salivary gland, skeletal muscle, spinal cord, testis, thymus, thyroid, trachea and uterus. Strongly expressed in peripheral blood leukocytes and spleen and, to a lesser extent, in colon. Specifically coexpressed with IL18R1 in T-helper 1 (Th1)cells.

Post-translational modifications. N-glycosylated.

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

Induction. Induced by IFN-alpha and IL12/interleukin-12 in natural killer (NK) cells and T-cells.

Similarity. Belongs to the interleukin-1 receptor family.

Isoforms (4)

UniProt ID	Names	Canonical?
O95256-1	1	yes
O95256-2	2
O95256-3	3, IL-18RAPshort
O95256-4	4

RefSeq proteins (5): NP_001380415, NP_001380416, NP_001380417, NP_001380418, NP_003844 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR003599	Ig_sub	Domain
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, PF18452

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (72 total): strand 28, helix 11, mutagenesis site 6, disulfide bond 5, splice variant 5, glycosylation site 4, turn 3, domain 3, topological domain 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7FCH	X-RAY DIFFRACTION	1.88
3WO4	X-RAY DIFFRACTION	3.1
6KN9	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95256-F1	77.78	0.34

Antibody-complex structures (SAbDab): 1 — 6KN9

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): 493

Disulfide bonds (5): 46–126, 155–180, 175–221, 180–221, 273–337

Glycosylation sites (4): 119, 152, 345, 21

Mutagenesis-validated functional residues (6):

Position	Phenotype
15–176	impairs il18 receptor signaling via nf-kappa-b.
167	decreases binding to the preformed binary complex of il18 and il18r1.
210	decreases binding to the preformed binary complex of il18 and il18r1. impairs il18 receptor signaling via nf-kappa-b; wh
212	abolishes binding to the preformed binary complex of il18 and il18r1. impairs il18 receptor signaling via nf-kappa-b; wh
214	decreases binding to the preformed binary complex of il18 and il18r1. impairs il18 receptor signaling via nf-kappa-b; wh
313	decreases binding to the preformed binary complex of il18 and il18r1. decreases il18 receptor signaling via nf-kappa-b.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9012546	Interleukin-18 signaling

MSigDB gene sets: 344 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, chr2q12, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GNF2_ZAP70, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (13): adaptive immune response (GO:0002250), inflammatory response (GO:0006954), immune response (GO:0006955), cell population proliferation (GO:0008283), interleukin-18-mediated signaling pathway (GO:0035655), neutrophil activation (GO:0042119), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), cellular response to hydrogen peroxide (GO:0070301), immune system process (GO:0002376), signal transduction (GO:0007165), cellular response to cytokine stimulus (GO:0071345), cellular response to interleukin-18 (GO:0071351)

GO Molecular Function (6): coreceptor activity (GO:0015026), interleukin-18 receptor activity (GO:0042008), NAD+ nucleosidase activity, cyclic ADP-ribose generating (GO:0061809), protein binding (GO:0005515), hydrolase activity (GO:0016787), signaling receptor activity (GO:0038023)

GO Cellular Component (4): plasma membrane (GO:0005886), cell surface (GO:0009986), interleukin-18 receptor complex (GO:0045092), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-1 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cellular anatomical structure	2
immune response	1
defense response	1
immune system process	1
response to stimulus	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-18	1
granulocyte activation	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
biological_process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to cytokine	1
response to interleukin-18	1
cellular response to cytokine stimulus	1
signaling receptor activity	1
cytokine receptor activity	1
interleukin-18-mediated signaling pathway	1
interleukin-18 binding	1
hydrolase activity, hydrolyzing N-glycosyl compounds	1
binding	1
catalytic activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

1666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL18RAP	IL18	Q14116	996
IL18RAP	IL18R1	Q13478	987
IL18RAP	IL32	P24001	807
IL18RAP	IL18BP	O95998	783
IL18RAP	IL1RAP	Q9NPH3	720
IL18RAP	IL1F10	Q8WWZ1	667
IL18RAP	IL1A	P01583	659
IL18RAP	GZMA	P12544	623
IL18RAP	IL1B	P01584	622
IL18RAP	MYD88	P78397	608
IL18RAP	IL37	Q9NZH6	570
IL18RAP	IL1R1	P14778	550
IL18RAP	IL1RL2	Q9HB29	546
IL18RAP	TAGAP	Q8N103	544
IL18RAP	PUS10	Q3MIT2	539

IntAct

9 interactions, top by confidence:

A	B	Type	Score
IL18RAP	WFS1	psi-mi:“MI:0915”(physical association)	0.610
WFS1	IL18RAP	psi-mi:“MI:0915”(physical association)	0.610
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
IL18RAP	PIGA	psi-mi:“MI:0914”(association)	0.350
TRIM54	IL18RAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): IL18RAP (Reconstituted Complex), PIGA (Affinity Capture-MS), PIGH (Affinity Capture-MS), IL18RAP (Two-hybrid), PIGA (Affinity Capture-MS), PIGH (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, A0JM41, A2VD98, B0CLX4, B6ZK77, D3YX43, F1LW30, O00241, O18906, O54901, O88775, O95256, P00545, P04218, P0C673, P10522, P13369, P17948, P21995, P27931, P35916, P35917, P35969, P37301, P42071, P42703, P53767, Q08DK1, Q15762, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5U2P2, Q5VJ70, Q6GMZ9, Q6PCB8, Q6X936, Q7TSN7

Diamond homologs: B2LT61, B2LT62, B2LT64, B2LT65, B3Y613, B3Y614, B3Y615, B3Y618, B5T267, O00206, O60603, O95256, P0DUE1, P10810, P34595, P39937, P58727, Q0GC71, Q0ZUL9, Q13478, Q15399, Q28680, Q2PZH4, Q2V897, Q2V898, Q4V892, Q5I2M3, Q5I2M4, Q61098, Q63691, Q689D1, Q68Y56, Q6GV17, Q6R5N8, Q6T752, Q704V6, Q8SPE8, Q8SPE9, Q95LA9, Q95M53

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1845 predictions. Top by Δscore:

Variant	Effect	Δscore
2:102424026:GACAT:G	donor_gain	1.0000
2:102424059:G:GT	donor_gain	1.0000
2:102441310:A:AG	acceptor_gain	1.0000
2:102441311:G:GA	acceptor_gain	1.0000
2:102445185:TCA:T	acceptor_loss	1.0000
2:102445187:A:AG	acceptor_gain	1.0000
2:102445187:A:G	acceptor_loss	1.0000
2:102445188:G:GA	acceptor_gain	1.0000
2:102445188:GT:G	acceptor_gain	1.0000
2:102445188:GTA:G	acceptor_gain	1.0000
2:102445188:GTAT:G	acceptor_gain	1.0000
2:102445188:GTATT:G	acceptor_gain	1.0000
2:102445337:GGAG:G	donor_gain	1.0000
2:102445338:G:GT	donor_gain	1.0000
2:102445339:AGGTA:A	donor_loss	1.0000
2:102445341:GTA:G	donor_loss	1.0000
2:102445342:T:G	donor_loss	1.0000
2:102447051:ACT:A	acceptor_gain	1.0000
2:102447064:CCACA:C	acceptor_loss	1.0000
2:102447065:CACAG:C	acceptor_loss	1.0000
2:102447067:CAGTG:C	acceptor_loss	1.0000
2:102447068:A:AG	acceptor_gain	1.0000
2:102447068:AGT:A	acceptor_gain	1.0000
2:102447069:G:GA	acceptor_gain	1.0000
2:102447069:GT:G	acceptor_gain	1.0000
2:102447069:GTG:G	acceptor_gain	1.0000
2:102447069:GTGGT:G	acceptor_gain	1.0000
2:102447203:TGGGG:T	donor_gain	1.0000
2:102447204:GGGG:G	donor_gain	1.0000
2:102447204:GGGGG:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000037389 (2:102451667 G>T), RS1000038844 (2:102424596 C>T), RS1000166264 (2:102421465 A>C), RS1000208207 (2:102435424 T>C), RS1000362453 (2:102441436 T>C), RS1000397734 (2:102428275 G>T), RS1000428680 (2:102428064 T>A), RS1000552898 (2:102429492 T>C), RS1000656233 (2:102434090 A>T), RS1000727585 (2:102445907 C>A), RS1000776022 (2:102434354 G>A), RS1001126963 (2:102417586 T>A,C), RS1001280615 (2:102431650 G>A,T), RS1001288995 (2:102419141 T>C,G), RS1001513873 (2:102430888 T>C)

Disease associations

OMIM: gene MIM:604509 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000157_6	Celiac disease	4.000000e-09
GCST000612_30	Celiac disease	1.000000e-15
GCST000879_29	Crohn’s disease	2.000000e-12
GCST001709_2	Atopic dermatitis	8.000000e-18
GCST001725_46	Inflammatory bowel disease	3.000000e-20
GCST002084_2	Allergic sensitization	5.000000e-11
GCST002166_10	Serum protein levels (sST2)	2.000000e-08
GCST002772_2	Leprosy	2.000000e-23
GCST003129_29	Primary biliary cholangitis	5.000000e-09
GCST003184_19	Atopic dermatitis	9.000000e-07
GCST003184_24	Atopic dermatitis	2.000000e-12
GCST003184_33	Atopic dermatitis	2.000000e-13
GCST004131_93	Inflammatory bowel disease	5.000000e-11
GCST004132_63	Crohn’s disease	6.000000e-11
GCST004632_129	Lymphocyte percentage of white cells	4.000000e-09
GCST004938_4	Liver fibrosis in pediatric non-alcoholic fatty acid liver disease	8.000000e-06
GCST005523_8	Celiac disease	1.000000e-16
GCST005752_7	Systemic lupus erythematosus	4.000000e-06
GCST005851_3	Delirium	1.000000e-08
GCST006585_2649	Blood protein levels	2.000000e-07
GCST007400_8	Systemic lupus erythematosus	1.000000e-07
GCST007563_2	Allergic disease (asthma, hay fever or eczema)	4.000000e-24
GCST007564_34	Asthma or allergic disease (pleiotropy)	2.000000e-27
GCST008916_108	Asthma	1.000000e-22
GCST008916_115	Asthma	8.000000e-09
GCST008916_29	Asthma	2.000000e-60
GCST009759_1	Extranodal natural killer T-cell lymphoma (nasal type)	3.000000e-16
GCST009798_51	Asthma	8.000000e-43
GCST009798_6	Asthma	4.000000e-51
GCST90002380_130	Basophil percentage of white cells	7.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005298	allergic sensitization measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4804253 (PROTEIN COMPLEX)

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases expression, decreases expression, decreases reaction, affects response to substance, affects cotreatment	3
sulforaphane	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
MT19c compound	increases expression	1
Rosuvastatin Calcium	decreases expression, decreases reaction	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	affects expression, affects cotreatment, increases expression	1
Arsenic	affects expression, increases abundance	1
Cacodylic Acid	affects expression, increases abundance	1
Estradiol	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Nickel	increases expression	1
Silicon Dioxide	increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6U6	Genomeditech HEK-293 H_IL18 Reporter	Transformed cell line	Female
CVCL_UF33	HEK-Blue IL-18	Transformed cell line	Female

Clinical trials (associated diseases)

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