IL1R2

Summary

IL1R2 (interleukin 1 receptor type 2, HGNC:5994) is a protein-coding gene on chromosome 2q11.2, encoding Interleukin-1 receptor type 2 (P27930). Non-signaling receptor for IL1A, IL1B and IL1RN.

The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage.

Source: NCBI Gene 7850 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_004633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5994
Approved symbol	IL1R2
Name	interleukin 1 receptor type 2
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	CD121b
Ensembl gene	ENSG00000115590
Ensembl biotype	protein_coding
OMIM	147811
Entrez	7850

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000332549, ENST00000393414, ENST00000441002, ENST00000457817, ENST00000464994, ENST00000474085, ENST00000482658, ENST00000485335, ENST00000493749, ENST00000909823, ENST00000909824, ENST00000909825, ENST00000909826, ENST00000909827, ENST00000909828, ENST00000909829, ENST00000966319, ENST00000966320, ENST00000966321

RefSeq mRNA: 2 — MANE Select: NM_004633 NM_001261419, NM_004633

CCDS: CCDS2054, CCDS58719

Canonical transcript exons

ENST00000332549 — 9 exons

Exon	Start	End
ENSE00000772413	102015871	102016051
ENSE00000772415	102022187	102022249
ENSE00001833197	101991960	101992011
ENSE00001916274	102028226	102028544
ENSE00003504957	102024533	102024668
ENSE00003621809	102026111	102026253
ENSE00003625128	102009562	102009826
ENSE00003677077	102008515	102008642
ENSE00003784695	102019638	102019812

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 98.39.

FANTOM5 (CAGE): breadth broad, TPM avg 9.0805 / max 2914.3294, expressed in 394 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21653	7.1458	298
21652	1.1102	90
21657	0.4783	92
21654	0.1554	29
21660	0.0647	19
21661	0.0431	16
21664	0.0286	9
21662	0.0224	8
21658	0.0212	8
21659	0.0107	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.39	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.27	gold quality
decidua	UBERON:0002450	97.84	gold quality
pharyngeal mucosa	UBERON:0000355	97.68	gold quality
colonic mucosa	UBERON:0000317	97.28	gold quality
blood	UBERON:0000178	97.27	gold quality
right lung	UBERON:0002167	97.18	gold quality
epithelium of nasopharynx	UBERON:0001951	97.15	gold quality
penis	UBERON:0000989	95.97	gold quality
cervix squamous epithelium	UBERON:0006922	95.93	gold quality
oral cavity	UBERON:0000167	95.52	gold quality
esophagus squamous epithelium	UBERON:0006920	94.53	gold quality
lower esophagus mucosa	UBERON:0035834	94.35	gold quality
epithelium of esophagus	UBERON:0001976	93.73	gold quality
mammalian vulva	UBERON:0000997	93.67	gold quality
periodontal ligament	UBERON:0008266	93.60	gold quality
tongue squamous epithelium	UBERON:0006919	93.35	gold quality
esophagus mucosa	UBERON:0002469	93.34	gold quality
spleen	UBERON:0002106	93.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.04	gold quality
rectum	UBERON:0001052	92.76	gold quality
squamous epithelium	UBERON:0006914	92.55	gold quality
upper leg skin	UBERON:0004262	92.46	gold quality
nipple	UBERON:0002030	91.80	gold quality
mucosa of transverse colon	UBERON:0004991	91.47	gold quality
cervix epithelium	UBERON:0004801	91.05	gold quality
upper lobe of left lung	UBERON:0008952	90.76	gold quality
upper lobe of lung	UBERON:0008948	90.12	gold quality
upper arm skin	UBERON:0004263	89.42	gold quality
skin of abdomen	UBERON:0001416	89.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	1336.82
E-HCAD-1	yes	527.78
E-MTAB-8410	yes	10.49
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, GLI2

Literature-anchored findings (GeneRIF, showing 40)

• reduced levels of mRNA in the endometrium of women suffering from endometriosis reveals a profound defect in gene expression with reduced capability of endometrial tissue to down-regulate IL-1 activity (PMID:11804955)
• the unique sIL1R-II binding ability of human IL-1beta is due to a single amino acid difference compared with monkey IL-1beta (PMID:12356774)
• findings point toward a deficiency in the mechanisms involved in the down-regulation of IL-1 actions at the systemic level and reveal soluble interleukin-1 receptor type II as a key factor involved in that process (PMID:12372465)
• to evaluate whether the interleukin (IL)-1 decoy receptor (R)is correlated with severity of infection in critically ill patients and reflects the activation of anti-inflammatory pathways by glucocorticoid hormones (PMID:12377932)
• soluble form of IL-1R AcP contributes to the antagonism of IL-1 action by the type II decoy receptor (PMID:12530978)
• The type II IL-1 decoy receptor acts as a scavenger of IL-1, representing a novel autoregulatory mechanism of the IL-1 system in neutrophils. (PMID:12794127)
• serum IL-1 alpha and IL-1 soluble receptor type 2 levels in women with ovarian cancers were significantly higher than those in cervical cancer, and in patients with benign disorders, and in healthy control (PMID:14674121)
• a reduced release of sIL-1RII by the endometrial tissue of women with endometriosis and revealed a proteolytic post-translational mechanism which may be involved in the down-regulation of IL-1RII levels (PMID:15705625)
• Increased circulating levels of interleukin 1 receptor, type II is associated with Hepatitis C virus positive patients and with those affected also by non-Hodgkin’s lymphoma and cryoglobulinemia syndrome (PMID:16596202)
• These findings reveal that nuclear localization of pre-IL-1alpha depends on the binding to HAX-1 and that biological activities might be elicited by the binding to both HAX-1 and IL-1RII in SSc fibroblasts. (PMID:16971486)
• BACE1 and BACE2 may act as alternative alpha-secretase-like proteases in proteolytic processing of IL-1R2 and APP (PMID:17307738)
• decreased IL1R2 expression is predominant in the eutopic and ectopic endometrium of women with endometriosis when compared with normal women. (PMID:17324958)
• Suggest that IL-1RII can neutralize IL-1 beta and counteract its effect on endometrial stromal cells, and may provide a new clinical strategy for the treatment of endometriosis. (PMID:17482186)
• Abnormal interleukin 1 receptor types I and II gene expression in eutopic and ectopic endometrial tissues of women with endometriosis. (PMID:17517439)
• Chorionic gonadotropin down-regulates the expression of the decoy inhibitory interleukin 1 receptor type II in human endometrial epithelial cells. (PMID:17702847)
• Levels of interleukin-1beta and Il1R2in the peritoneal fluid of normal women and patients with endometriosis suffering from pelvic pain and infertility. (PMID:17919610)
• IL1R2 was greatly decreased with future rejection and FLT3, ITGAM, and PDCD1 showed borderline changes in future cardiac rejections. (PMID:18096476)
• was detected more often in chronic periodontitis gingival crevicular fluid than in aggressive periodontitis gingival crevicular fluid, and there was no correlation between gingival crevicular fluid concentration and clinical parameters. (PMID:18315432)
• Results suggest that interleukin-1 receptor type II overexpression is likely, through activation of the IL-1alpha precursor pathway, to enhance cell migration. (PMID:19026558)
• Alternate splicing of interleukin-1 receptor type II in vitro correlates with clinical glucocorticoid responsiveness in patients with autoimmune inner ear disease. (PMID:19401759)
• IL1R2 showed significant associations with Aspirin-intolerant asthma. (PMID:19489917)
• ANTXR2 and IL-1R2 polymorphisms are not associated with ankylosing spondylitis in Chinese Han population. (PMID:20652271)
• As already reported in endometriotic cells, endometrioid ovarian cancer cells exhibit a decrease in the expression of IL-1RII. These findings highlight a common signature between endometrioid ovarian cancer and implants of endometriosis. (PMID:21083841)
• Results suggest that under atherogenic conditions, there is a decrease in IL-1R2 expression in monocytes/macrophages and in the vascular wall that may facilitate IL-1 signaling. (PMID:21683158)
• interactions between TLR4 and IL-1R2 are associated with cervical pro-inflammatory cytokine concentrations. (PMID:21704385)
• The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (PMID:22048455)
• Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1alpha, controlling necrosis-induced sterile inflammation. (PMID:23395675)
• Data indicate a significant increase in the levels of IL-8, TNF-alpha and IL-1R2 in the CSF of both meningitis groups as compared to controls, and the concentrations of IFN-gamma and IL-1 differed significantly only between the mumps group and control. (PMID:24313836)
• First study evaluating for associations between cytokine gene variations and the development of persistent breast pain in women following breast cancer surgery: 1 SNP (IL1R2 rs11674595) and 1 haplotype (IL10 haplotype A8) were associated with pain (PMID:24411993)
• A genetic susceptibility locus for AgP may lie within or close to the IL1R2 locus in Japanese aggressive periodontitis. (PMID:24818754)
• results suggested that IL1R2 could have oncogenic potential in osteosarcoma (PMID:25432697)
• Cerebrospinal fluid soluble interleukin-1 Receptor II, but not log interleukin-6, levels were positively correlated with a composite measure of aggression. (PMID:25650410)
• This is the first detection that the genetic variation rs2302589 in IL-1R2 gene was associated with ankylosing spondylitis in Northern Han Chinese. (PMID:25736356)
• Suggest IL-1R2 as potential biomarker of acute respiratory distress syndrome. (PMID:25849954)
• Data show that interleukin-1 receptor type 2 (IL1R2) forms a complex with c-Fos proto-oncogene protein and activates the interleukin-6 (IL-6) and vascular endothelial growth factor A (VEGF-A) promoters. (PMID:26209639)
• Interleukin-1alpha Activity in Necrotic Endothelial Cells Is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2 (PMID:26324711)
• these results reveal that the IL-1/IL-1R2 axis is differentially regulated in the remitting intestinal mucosa of ulcerative colitis patients (PMID:26530134)
• IL1R2 rs2310173 genotype GT was mildly protective against ankylosing spontylitis only in HLA-B27-negative patients. (PMID:26590821)
• reduced risk of preterm birth in Indian women with the minor allele of rs2072476 polymorphism (PMID:26607028)
• IL1R2 hypomethylation and androgen receptor hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to excessive daytime sleepiness in Obstructive Sleep Apnea (PMID:26888452)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il1r2	ENSMUSG00000026073
rattus_norvegicus	Il1r2	ENSRNOG00000014378

Paralogs (10): LAG3 (ENSG00000089692), IL1R1 (ENSG00000115594), IL1RL2 (ENSG00000115598), IL1RL1 (ENSG00000115602), IL18R1 (ENSG00000115604), IL18RAP (ENSG00000115607), IL1RAPL1 (ENSG00000169306), SIGIRR (ENSG00000185187), IL1RAPL2 (ENSG00000189108), IL1RAP (ENSG00000196083)

Protein

Protein identifiers

Interleukin-1 receptor type 2 — P27930 (reviewed: P27930)

Alternative names: CD121 antigen-like family member B, CDw121b, IL-1 type II receptor, Interleukin-1 receptor beta, Interleukin-1 receptor type II

All UniProt accessions (2): C9JNR0, P27930

UniProt curated annotations — full annotation on UniProt →

Function. Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competitive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.

Subunit / interactions. Associates with IL1RAP to form a non-signaling interleukin-1 receptor complex.

Subcellular location. Secreted Cell membrane.

Post-translational modifications. A soluble form (sIL1R2) can also be produced by proteolytic cleavage at the cell surface (shedding) involving a metalloproteinase; hovever, several sIL1R2 forms ranging from 45 and 60 kDa are reported.

Similarity. Belongs to the interleukin-1 receptor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P27930-1	Long	yes
P27930-2	Short

RefSeq proteins (2): NP_001248348, NP_004624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR004074	IL-1_rcpt_I/II-typ	Family
IPR004077	IL-1_rcpt_II-typ	Family
IPR007110	Ig-like_dom	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015621	IL-1_rcpt_fam	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00047

UniProt features (55 total): strand 26, glycosylation site 5, disulfide bond 4, sequence conflict 3, helix 3, domain 3, chain 2, sequence variant 2, topological domain 2, signal peptide 1, splice variant 1, turn 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3O4O	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27930-F1	83.97	0.60

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 (4): 28–116, 50–108, 152–207, 258–326

Glycosylation sites (5): 66, 72, 112, 219, 277

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: 350 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, JAEGER_METASTASIS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, KEGG_MAPK_SIGNALING_PATHWAY, PID_IL1_PATHWAY, MODULE_317, GOCC_CELL_SURFACE, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (8): immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), negative regulation of protein processing (GO:0010955), protein processing (GO:0016485), negative regulation of interleukin-1 alpha production (GO:0032690), negative regulation of cytokine production involved in inflammatory response (GO:1900016), negative regulation of interleukin-1-mediated signaling pathway (GO:2000660), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (4): interleukin-1 receptor activity (GO:0004908), interleukin-1, type II, blocking receptor activity (GO:0004910), interleukin-1 binding (GO:0019966), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

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
immune system process	1
response to stimulus	1
signal transduction	1
protein processing	1
negative regulation of proteolysis	1
regulation of protein processing	1
negative regulation of protein maturation	1
proteolysis	1
protein maturation	1
interleukin-1 alpha production	1
regulation of interleukin-1 alpha production	1
negative regulation of interleukin-1 production	1
negative regulation of cytokine production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
negative regulation of cytokine-mediated signaling pathway	1
interleukin-1-mediated signaling pathway	1
regulation of interleukin-1-mediated signaling pathway	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cytokine receptor activity	1
interleukin-1 binding	1
interleukin-1 receptor activity	1
growth factor binding	1
cytokine binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2435 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL1R2	IL1A	P01583	996
IL1R2	IL1B	P01584	996
IL1R2	IL1RAP	Q9NPH3	975
IL1R2	IL1R1	P14778	971
IL1R2	IL1RN	P18510	915
IL1R2	TNF	P01375	783
IL1R2	IL10	P22301	780
IL1R2	IFNG	P01579	763
IL1R2	IL6	P05231	733
IL1R2	IL18	Q14116	682
IL1R2	IL6R	P08887	680
IL1R2	CXCL8	P10145	664
IL1R2	ANTXR2	P58335	659
IL1R2	OPRM1	P35372	658
IL1R2	IL13	P35225	641

IntAct

23 interactions, top by confidence:

A	B	Type	Score
IL1RAP	IL1B	psi-mi:“MI:0915”(physical association)	0.760
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
IL1A	IL1R2	psi-mi:“MI:0915”(physical association)	0.660
IL1A	IL1R2	psi-mi:“MI:2364”(proximity)	0.660
IL1A	HAX1	psi-mi:“MI:0914”(association)	0.620
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
PRR30	IL1R2	psi-mi:“MI:0915”(physical association)	0.400
IL1R2	TNFSF13B	psi-mi:“MI:0915”(physical association)	0.400
Adam17	IL1R2	psi-mi:“MI:0915”(physical association)	0.400
IL1R2	QSOX1	psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350
	IL1R2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (92): IL1R2 (Co-localization), EXOC6B (Affinity Capture-MS), CCDC51 (Affinity Capture-MS), EXOC6 (Affinity Capture-MS), NUDT16 (Affinity Capture-MS), EXOC5 (Affinity Capture-MS), EXOC7 (Affinity Capture-MS), EXOC1 (Affinity Capture-MS), TRMU (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), EXOC3 (Affinity Capture-MS), NDUFA12 (Affinity Capture-MS), EXOC8 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS)

ESM2 similar proteins: A5D7V5, O62643, O75144, O88875, P01830, P01831, P01909, P04216, P08508, P09793, P12318, P12319, P14778, P15509, P16410, P27645, P27930, P30433, P31994, P31995, P33681, P42069, P42070, P42072, P50283, Q07212, Q0VCS6, Q28110, Q3TEW6, Q58DF9, Q63203, Q6AYT8, Q6Q8B3, Q6XJV4, Q6XJV6, Q75VT8, Q7YR73, Q8BTP3, Q8NC01, Q8SPV8

Diamond homologs: A0A7H0DNG1, O57261, P21116, P25212, P27930, P27931, P43303, Q04523, Q29612, P13504, P14778, Q02955, Q62929, Q9ERS7, Q9HB29, Q9NP60, Q61790, Q9ERS6, A8QMS7, B2LT61, B2LT62, B2LT64, B2LT65, B3SRQ2, B3Y613, B3Y614, B3Y615, B3Y618, B5T267, C8BKC7, O60603, P08953, P22366, P59822, P59823, P59824, P60029, Q0GC71, Q0ZUL9, Q13478

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IL1B	down-regulates	IL1R2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1550 predictions. Top by Δscore:

Variant	Effect	Δscore
2:102009825:AGGTA:A	donor_loss	1.0000
2:102009826:GGT:G	donor_loss	1.0000
2:102009828:T:G	donor_loss	1.0000
2:102019811:GA:G	donor_gain	1.0000
2:102019813:G:GG	donor_gain	1.0000
2:102022175:C:G	acceptor_gain	1.0000
2:102022176:A:AG	acceptor_gain	1.0000
2:102022177:T:G	acceptor_gain	1.0000
2:102022185:A:AG	acceptor_gain	1.0000
2:102022186:G:GA	acceptor_gain	1.0000
2:102024531:A:AG	acceptor_gain	1.0000
2:102024531:AG:A	acceptor_gain	1.0000
2:102024532:G:GG	acceptor_gain	1.0000
2:102024532:GG:G	acceptor_gain	1.0000
2:102024664:CGCCA:C	donor_gain	1.0000
2:102024665:GCCA:G	donor_gain	1.0000
2:102024665:GCCAG:G	donor_gain	1.0000
2:102024668:AGTA:A	donor_loss	1.0000
2:102024669:G:GG	donor_gain	1.0000
2:102024669:GTAAG:G	donor_loss	1.0000
2:102024670:TAAGT:T	donor_loss	1.0000
2:102024671:AA:A	donor_loss	1.0000
2:102026106:CTCA:C	acceptor_loss	1.0000
2:102026107:TCA:T	acceptor_loss	1.0000
2:102026108:CAG:C	acceptor_loss	1.0000
2:102026109:A:AG	acceptor_gain	1.0000
2:102026109:AG:A	acceptor_gain	1.0000
2:102026109:AGGG:A	acceptor_loss	1.0000
2:102026110:G:GG	acceptor_gain	1.0000
2:102026110:GG:G	acceptor_gain	1.0000

AlphaMissense

2584 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:102024603:G:C	W274C	0.994
2:102024603:G:T	W274C	0.994
2:102026199:T:A	C326S	0.993
2:102026200:G:C	C326S	0.993
2:102009701:G:C	W69C	0.991
2:102009701:G:T	W69C	0.991
2:102016045:G:C	W169C	0.991
2:102016045:G:T	W169C	0.991
2:102016043:T:A	W169R	0.990
2:102016043:T:C	W169R	0.990
2:102024553:T:A	C258S	0.990
2:102024554:G:C	C258S	0.990
2:102019743:T:A	C207S	0.988
2:102019744:G:C	C207S	0.988
2:102024554:G:A	C258Y	0.988
2:102024601:T:A	W274R	0.988
2:102024601:T:C	W274R	0.988
2:102015992:T:A	C152S	0.987
2:102015992:T:C	C152R	0.987
2:102015993:G:C	C152S	0.987
2:102009816:T:A	C108S	0.986
2:102009817:G:C	C108S	0.986
2:102026152:T:C	L310S	0.986
2:102019743:T:C	C207R	0.985
2:102024553:T:C	C258R	0.985
2:102026199:T:C	C326R	0.985
2:102024555:T:G	C258W	0.984
2:102019745:T:G	C207W	0.983
2:102009818:C:G	C108W	0.981
2:102019744:G:A	C207Y	0.981

dbSNP variants (sampled 300 via entrez): RS1000091265 (2:101998067 G>A,T), RS1000419466 (2:101990782 C>A), RS1000430549 (2:102014884 TC>T), RS1000676586 (2:102002214 C>G,T), RS1000692143 (2:101996333 C>A), RS1000938784 (2:102007635 G>C,T), RS1000981727 (2:102021245 A>C,G), RS1000990910 (2:101995817 C>T), RS1001002889 (2:102023922 T>G), RS1001049767 (2:102009324 G>A), RS1001245128 (2:102007935 C>T), RS1001247463 (2:101994008 G>A,T), RS1001346301 (2:101992014 G>C), RS1001400619 (2:101999178 A>G), RS1001462445 (2:101991828 C>T)

Disease associations

OMIM: gene MIM:147811 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000563_2	Ankylosing spondylitis	5.000000e-07
GCST000964_7	Ulcerative colitis	3.000000e-12
GCST001725_46	Inflammatory bowel disease	3.000000e-20
GCST001877_12	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	3.000000e-06
GCST002147_11	Fibrinogen	3.000000e-08
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
GCST004902_16	Parkinson’s disease	5.000000e-11
GCST005529_26	Ankylosing spondylitis	4.000000e-06
GCST005529_65	Ankylosing spondylitis	1.000000e-06
GCST005529_8	Ankylosing spondylitis	1.000000e-07
GCST005537_160	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-14
GCST006585_2165	Blood protein levels	7.000000e-55
GCST007615_13	C-reactive protein levels	1.000000e-09
GCST008916_13	Asthma	8.000000e-13
GCST008916_29	Asthma	2.000000e-60
GCST010991_28	Parkinson’s disease	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	5
sodium arsenite	decreases expression, increases expression	4
Ozone	increases expression, affects cotreatment, affects expression, increases abundance	4
Tetrachlorodibenzodioxin	increases expression	4
Tobacco Smoke Pollution	increases expression	4
2-chloroethyl ethyl sulfide	decreases expression	2
Arsenic Trioxide	increases expression	2
Acetaminophen	decreases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Eugenol	increases expression	2
Lipopolysaccharides	affects cotreatment, decreases expression, increases expression	2
Methotrexate	decreases expression, increases expression	2
Mustard Gas	increases alkylation, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
geraniol	increases expression	1
lead acetate	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
arsenite	affects expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
nickel sulfate	increases expression	1
zinc sulfide	decreases expression, affects cotreatment	1
resorcinol	increases expression	1

Clinical trials (associated diseases)

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