SIGIRR

Summary

SIGIRR (single Ig and TIR domain containing, HGNC:30575) is a protein-coding gene on chromosome 11p15.5, encoding Single Ig IL-1-related receptor (Q6IA17). Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways.

Involved in negative regulation of Toll signaling pathway. Located in membrane.

Source: NCBI Gene 59307 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_001135054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30575
Approved symbol	SIGIRR
Name	single Ig and TIR domain containing
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	TIR8, IL-1R8
Ensembl gene	ENSG00000185187
Ensembl biotype	protein_coding
OMIM	605478
Entrez	59307

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 26 protein_coding, 8 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000332725, ENST00000397632, ENST00000431843, ENST00000525070, ENST00000525299, ENST00000526395, ENST00000526788, ENST00000527136, ENST00000527295, ENST00000527987, ENST00000528058, ENST00000528116, ENST00000528209, ENST00000528536, ENST00000528698, ENST00000528845, ENST00000529486, ENST00000530494, ENST00000530683, ENST00000531205, ENST00000534145, ENST00000534217, ENST00000714411, ENST00000714412, ENST00000714413, ENST00000714414, ENST00000714415, ENST00000714416, ENST00000887764, ENST00000887765, ENST00000887766, ENST00000887767, ENST00000887768, ENST00000887769, ENST00000887770, ENST00000887771, ENST00000887772, ENST00000962935, ENST00000962936, ENST00000962937

RefSeq mRNA: 3 — MANE Select: NM_001135054 NM_001135053, NM_001135054, NM_021805

CCDS: CCDS31325

Canonical transcript exons

ENST00000431843 — 10 exons

Exon	Start	End
ENSE00001769635	414823	414999
ENSE00004023913	407817	407957
ENSE00004023914	409868	410027
ENSE00004023915	405716	406059
ENSE00004023916	407425	407568
ENSE00004023920	406349	406538
ENSE00004023921	406843	406993
ENSE00004023928	407062	407164
ENSE00004023930	408073	408206
ENSE00004023931	408695	408893

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.8458 / max 240.4921, expressed in 1785 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117750	17.3826	1650
117748	3.8534	1187
117751	3.3902	429
117753	1.7614	389
117754	0.9122	345
117755	0.8048	345
117752	0.5942	232
117749	0.1469	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.32	gold quality
mucosa of transverse colon	UBERON:0004991	98.25	gold quality
right lobe of liver	UBERON:0001114	98.11	gold quality
right uterine tube	UBERON:0001302	97.73	gold quality
metanephros cortex	UBERON:0010533	97.42	gold quality
apex of heart	UBERON:0002098	96.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.85	gold quality
spleen	UBERON:0002106	96.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.57	gold quality
transverse colon	UBERON:0001157	96.32	gold quality
body of stomach	UBERON:0001161	95.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.64	gold quality
left uterine tube	UBERON:0001303	94.96	gold quality
small intestine	UBERON:0002108	94.93	gold quality
adult mammalian kidney	UBERON:0000082	94.77	gold quality
blood	UBERON:0000178	94.65	gold quality
lower esophagus	UBERON:0013473	94.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.51	gold quality
body of pancreas	UBERON:0001150	94.39	gold quality
lymph node	UBERON:0000029	94.36	gold quality
upper lobe of left lung	UBERON:0008952	94.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.28	gold quality
right lobe of thyroid gland	UBERON:0001119	94.21	gold quality
liver	UBERON:0002107	94.12	gold quality
right lung	UBERON:0002167	93.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.94	gold quality
lower esophagus mucosa	UBERON:0035834	93.73	gold quality
minor salivary gland	UBERON:0001830	93.64	gold quality
spinal cord	UBERON:0002240	93.63	gold quality
body of uterus	UBERON:0009853	93.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, IRF6, SP1

miRNA regulators (miRDB)

8 targeting SIGIRR, 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-6764-5P	99.75	67.89	2304
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-8083	95.93	67.55	694

Literature-anchored findings (GeneRIF, showing 34)

• SIGIRR inhibits IL-1R and TLR4-mediated signaling through different mechanisms (PMID:15866876)
• regulatory functions in inflammation and Th1/Th2 cell polarization (Review) (PMID:19699681)
• Data show that Sigirr overexpression depresses NF-B-mediated diverse TLR responses. (PMID:20130217)
• SIGIRR can inhibit TLR4, 5, and 9-mediated immune responses in human airway epithelial cells. (PMID:20364327)
• SIGIRR/TIR-8 is an inhibitor of Toll-like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritis (PMID:20506350)
• SIGIRR is expressed constitutively in intestinal epithelial cells to maintain gut innate immunity and then down-regulated during inflammation by inhibition of an SP1-mediated pathway. (PMID:21077278)
• These results suggest that PALM3 may function as an adaptor in the LPS- Toll-like receptor 4 signaling and the interaction of SIGIRR with PALM3 may partly account for the mechanism of the negatively regulatory effect of SIGIRR. (PMID:21187075)
• These results demonstrate a strong association of single-nucleotide polymorphisms in the PKP3-SIGIRR-TMEM16J gene region and tuberculosis in discovery and validation cohorts. (PMID:22223854)
• the tested variations of IRAK-M and SIGIRR genes do not confer a relevant role in the susceptibility to systemic lupus erythematosus in European-descent populations (PMID:22634523)
• The present study was undertaken to characterize responses of B cells from systemic lupus erythematosus patients to TLR7 and TLR9 stimulation and to explore the potential role of SIGIRR. (PMID:22952899)
• Lipopolysaccharide decreases SIGIRR expression by suppressing specificity protein 1 Sp1 via the TLR4-p38 pathway in monocytes and neutrophils. (PMID:24821721)
• An association was found in the SIGIRR rs7396562 polymorphism and systemic lupus erythematosus susceptibility in a Chinese population. (PMID:24826913)
• decreased numbers of SIGIRR-positive CD4+ T cells in SLE patients and its correlation with SLEDAI score as well as the clinical data suggest that SIGIRR may be involved in the pathogenesis of SLE. (PMID:25287661)
• IL-37 acts as an extracellular cytokine by binding to the IL-18 receptor but using the IL-1R8 for its anti-inflammatory properties. (PMID:25654981)
• IL-37 requires the receptors IL-18Ralpha and IL-1R8 to carry out its multifaceted anti-inflammatory program upon innate signal transduction. (PMID:25729923)
• To the best of our knowledge, this is one of the first reports of a phenotype associated with SIGIRR in humans. Our data provide novel mechanistic insight into the probable causation of necrotizing enterocolitis (PMID:25963006)
• Levels of SIGIRR are lower in human colorectal tumors, compared with nontumor tissues; tumors contain the dominant-negative isoform SIGIRR(DeltaE8). (PMID:26344057)
• SIGIRR predicts biochemical recurrence in patients with low Gleason score and low pathological stage prostate cancer. (PMID:26344417)
• Tir8/SIGIRR acts anti-inflammatory on different immune responses,its function in allergic asthma is a controversial issue, since anti- as well as pro-inflammatory effects have been reported (PMID:26561030)
• SIGIRR plays an important role in the negative regulation of LPS response and tolerance in human bladder epithelial cells, possibly through its impact on TLR-mediated signaling. (PMID:26634342)
• show by flow cytometry analysis, western blot, confocal microscopy, and quantitative real-time polymerase chain reaction that IL-1R8 is expressed on human and mouse platelets at high levels and on megakaryocytes. IL-1R8-deficient mice show normal levels of circulating platelets (PMID:27297888)
• Our results indicate that high IL-1R8 expression acts as a novel immunomodulatory mechanism leading to dysregulated immunity with important implications for breast cancer immunotherapy. (PMID:28533483)
• SIGIRR is both a negative regulator of TLR4 and a positive regulator of TLR7/8. (PMID:28869081)
• Specificity protein 1 modulates TGFbeta1/Smad signaling and negatively regulates SIGIRR protein production by macrophages after substance P stimulation. (PMID:29558695)
• The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection. (PMID:31149943)
• Immune response against Chlamydia trachomatis via toll-like receptors is negatively regulated by SIGIRR (PMID:32210474)
• Single immunoglobulin and Tollinterleukin1 receptor domain containing molecule protects against severe acute pancreatitis in vitro by negatively regulating the Tolllike receptor4 signaling pathway: A clinical and experimental study. (PMID:32945488)
• Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro. (PMID:33123603)
• MiR-340 suppresses CCl4-induced acute liver injury through exerting anti-inflammation targeting Sigirr. (PMID:33155227)
• IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8. (PMID:33391457)
• Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis. (PMID:34036103)
• IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway. (PMID:34083516)
• SIGIRR Mutation in Human Necrotizing Enterocolitis (NEC) Disrupts STAT3-Dependent microRNA Expression in Neonatal Gut. (PMID:34563711)
• IL-1R8: A molecular brake of anti-tumor and anti-viral activity of NK cells and ILC. (PMID:36753974)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sigirr	ENSDARG00000062204
mus_musculus	Sigirr	ENSMUSG00000025494
rattus_norvegicus	Sigirr	ENSRNOG00000015593

Paralogs (10): LAG3 (ENSG00000089692), IL1R2 (ENSG00000115590), IL1R1 (ENSG00000115594), IL1RL2 (ENSG00000115598), IL1RL1 (ENSG00000115602), IL18R1 (ENSG00000115604), IL18RAP (ENSG00000115607), IL1RAPL1 (ENSG00000169306), IL1RAPL2 (ENSG00000189108), IL1RAP (ENSG00000196083)

Protein

Protein identifiers

Single Ig IL-1-related receptor — Q6IA17 (reviewed: Q6IA17)

Alternative names: Single Ig IL-1R-related molecule, Single immunoglobulin domain-containing IL1R-related protein, Toll/interleukin-1 receptor 8

All UniProt accessions (8): A0AAQ5BI23, C9JFX4, E9PK23, E9PLG6, E9PSD9, Q6IA17, H0YDF8, H0YDR5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP.

Subunit / interactions. Interacts with IL1R1, IRAK1, TLR4, TLR5, TLR9 and TRAF6. Upon IL-1 stimulation found in a complex at least composed of IL1R1, SIGIRR, MYD88, IRAK1 and TRAF6. Upon stimulation with LPC found in a complex at least composed of TLR4, SIG1IR, MYD88, IRAK1 and TRAF6. Interacts with PALM3.

Subcellular location. Membrane.

Tissue specificity. Mainly expressed in epithelial tissues such as kidney, lung and gut.

Induction. Down-regulated during inflammation by inhibition of an SP1-mediated pathway.

Similarity. Belongs to the interleukin-1 receptor family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IA17-1	1	yes
Q6IA17-2	2

RefSeq proteins (3): NP_001128525, NP_001128526, NP_068577 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	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

Pfam: PF01582

UniProt features (18 total): glycosylation site 4, sequence variant 3, topological domain 2, domain 2, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IA17-F1	75.75	0.29

Functional residue map

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

Post-translational modifications (1): 383

Disulfide bonds (1): 32–98

Glycosylation sites (4): 86, 102, 31, 73

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-9008059	Interleukin-37 signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-446652	Interleukin-1 family signaling
R-HSA-449147	Signaling by Interleukins

MSigDB gene sets: 228 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, YANG_BREAST_CANCER_ESR1_LASER_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOCC_CELL_SURFACE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, RODRIGUES_NTN1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_RESPONSE_TO_INTERLEUKIN_1

GO Biological Process (9): negative regulation of cytokine-mediated signaling pathway (GO:0001960), acute-phase response (GO:0006953), cell surface receptor signaling pathway (GO:0007166), negative regulation of lipopolysaccharide-mediated signaling pathway (GO:0031665), negative regulation of chemokine production (GO:0032682), negative regulation of Toll signaling pathway (GO:0045751), negative regulation of interleukin-1-mediated signaling pathway (GO:2000660), signal transduction (GO:0007165), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Immune System	2
Toll-like Receptor Cascades	2
Toll Like Receptor 2 (TLR2) Cascade	2
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Interleukin-1 family signaling	1
Innate Immune System	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of signal transduction	3
signal transduction	2
cellular anatomical structure	2
regulation of cytokine-mediated signaling pathway	1
cytokine-mediated signaling pathway	1
negative regulation of response to cytokine stimulus	1
acute inflammatory response	1
negative regulation of response to biotic stimulus	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
negative regulation of response to external stimulus	1
negative regulation of cytokine production	1
chemokine production	1
regulation of chemokine production	1
Toll signaling pathway	1
regulation of Toll signaling pathway	1
negative regulation of cytokine-mediated signaling pathway	1
interleukin-1-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
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGIRR	IRAK1	P51617	956
SIGIRR	MYD88	P78397	919
SIGIRR	IL37	Q9NZH6	891
SIGIRR	TLR4	O00206	890
SIGIRR	IRAK3	Q9Y616	843
SIGIRR	IL18R1	Q13478	838
SIGIRR	TLR5	O60602	835
SIGIRR	IL33	O95760	827
SIGIRR	TRAF6	Q9Y4K3	824
SIGIRR	TIRAP	P58753	765
SIGIRR	IL36RN	Q9UBH0	745
SIGIRR	TOLLIP	Q9H0E2	743
SIGIRR	IL1A	P01583	692
SIGIRR	IL18	Q14116	649
SIGIRR	LY96	Q9Y6Y9	612

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SIGIRR	PALM3	psi-mi:“MI:0915”(physical association)	0.510
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
LGALS8	NPC1	psi-mi:“MI:0914”(association)	0.350
SIGIRR		psi-mi:“MI:0915”(physical association)	0.000
ENO2	SIGIRR	psi-mi:“MI:0915”(physical association)	0.000
SIGIRR	RPN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): SIGIRR (Affinity Capture-RNA), SIGIRR (Proximity Label-MS), SIGIRR (Affinity Capture-Western), SIGIRR (Affinity Capture-Western), SIGIRR (Affinity Capture-Western), IRAK1 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), SIGIRR (Affinity Capture-Western), SIGIRR (Two-hybrid), SIGIRR (Affinity Capture-MS), SIGIRR (Affinity Capture-MS), GSK3B (Affinity Capture-Western), SIGIRR (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A4FV98, A5D7B1, A5PK51, A6QLN9, A8MUP2, D3ZVU9, O15527, O35595, O75078, O95848, P57775, Q05B60, Q06643, Q14728, Q14CX5, Q1LZB9, Q27HK4, Q2T9T5, Q2TBS1, Q3UGX3, Q4R3I0, Q4V892, Q58CT4, Q5E9H2, Q5RCI5, Q5SUV1, Q5TM22, Q642A6, Q6IA17, Q6PCB0, Q6XQN6, Q862Z7, Q8N8L6, Q8R2R5, Q8R2Z5, Q8R366, Q8WUG5, Q95JH0, Q95JH2, Q969P0

Diamond homologs: A2TF48, A5HNF6, A8QMS7, B2LT64, B3SRQ2, B3Y678, B3Y679, B3Y680, B3Y681, B3Y682, B3Y683, B6CJX2, C8BKC7, P22366, Q28DJ2, Q4LBC6, Q599T9, Q5FWM2, Q5XJ85, Q61098, Q6IA17, Q6Y1S1, Q99836, Q9DF60, Q9JLZ8, Q9R1F8, Q9V477, Q9WV82, V5NAL9, P59822, Q61730, Q9NPH3, Q13478, P53355, B6ZK76, B6ZK77, P59823, P59824, P60029, Q4V892

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GSK3B	“down-regulates quantity by destabilization”	SIGIRR	phosphorylation
SIGIRR	“form complex”	“Interleukin-37 receptor-ligand complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1542 predictions. Top by Δscore:

Variant	Effect	Δscore
11:406857:T:TA	donor_gain	1.0000
11:407451:T:TA	donor_gain	1.0000
11:407566:CGT:C	acceptor_gain	1.0000
11:407569:C:CC	acceptor_gain	1.0000
11:407832:C:A	donor_gain	1.0000
11:407843:T:TA	donor_gain	1.0000
11:408065:C:CA	donor_gain	1.0000
11:406057:CAC:C	acceptor_gain	0.9900
11:406058:ACC:A	acceptor_loss	0.9900
11:406061:T:A	acceptor_loss	0.9900
11:406344:CATAC:C	donor_loss	0.9900
11:406345:ATAC:A	donor_loss	0.9900
11:406346:TA:T	donor_loss	0.9900
11:406347:A:AC	donor_gain	0.9900
11:406347:A:C	donor_loss	0.9900
11:406347:AC:A	donor_gain	0.9900
11:406348:C:CC	donor_gain	0.9900
11:406348:CC:C	donor_gain	0.9900
11:406357:C:CA	donor_gain	0.9900
11:406362:AGGGT:A	donor_gain	0.9900
11:406519:C:CT	acceptor_gain	0.9900
11:406519:C:T	acceptor_gain	0.9900
11:406520:A:T	acceptor_gain	0.9900
11:406547:C:CT	acceptor_gain	0.9900
11:407564:CCCGT:C	acceptor_gain	0.9900
11:407565:CCGT:C	acceptor_gain	0.9900
11:407565:CCGTC:C	acceptor_gain	0.9900
11:407566:CGTC:C	acceptor_gain	0.9900
11:407569:C:CG	acceptor_loss	0.9900
11:407570:T:A	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000187452 (11:410632 T>C,G), RS1000326718 (11:414440 C>T), RS1000378053 (11:406007 C>T), RS1000410653 (11:406276 G>A), RS1000589995 (11:413392 C>A), RS1000657201 (11:413527 C>T), RS1000798129 (11:406131 C>T), RS1001261276 (11:405752 G>A), RS1001601585 (11:419312 G>A,C,T), RS1001832007 (11:413464 C>A,T), RS1003239911 (11:417814 G>A), RS1003354635 (11:415659 T>C), RS1003423665 (11:409976 C>T), RS1003483573 (11:408054 C>A), RS1003596817 (11:407720 A>C,G)

Disease associations

OMIM: gene MIM:605478 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010241_283	Apolipoprotein A1 levels	6.000000e-09
GCST90002388_530	Lymphocyte count	3.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004587	lymphocyte count

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Aflatoxin B1	affects expression, decreases expression	2
methylmercuric chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
obeticholic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Allergens	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	affects cotreatment, increases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, decreases response to substance, increases secretion	1
Ribonucleotides	affects binding	1
Selenium	increases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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