IL10RA

Summary

IL10RA (interleukin 10 receptor subunit alpha, HGNC:5964) is a protein-coding gene on chromosome 11q23.3, encoding Interleukin-10 receptor subunit alpha (Q13651). Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.

The protein encoded by this gene is a receptor for interleukin 10. This protein is structurally related to interferon receptors. It has been shown to mediate the immunosuppressive signal of interleukin 10, and thus inhibits the synthesis of proinflammatory cytokines. This receptor is reported to promote survival of progenitor myeloid cells through the insulin receptor substrate-2/PI 3-kinase/AKT pathway. Activation of this receptor leads to tyrosine phosphorylation of JAK1 and TYK2 kinases. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene.

Source: NCBI Gene 3587 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inflammatory bowel disease 28 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 497 total — 15 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 10
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5964
Approved symbol	IL10RA
Name	interleukin 10 receptor subunit alpha
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HIL-10R, CDW210A, CD210a, CD210
Ensembl gene	ENSG00000110324
Ensembl biotype	protein_coding
OMIM	146933
Entrez	3587

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 retained_intron, 3 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000227752, ENST00000525467, ENST00000526544, ENST00000529924, ENST00000530178, ENST00000530761, ENST00000531365, ENST00000532009, ENST00000533700, ENST00000534335, ENST00000534574, ENST00000696732, ENST00000885116, ENST00000951964

RefSeq mRNA: 1 — MANE Select: NM_001558 NM_001558

CCDS: CCDS8388

Canonical transcript exons

ENST00000227752 — 7 exons

Exon	Start	End
ENSE00002200423	117998715	118001483
ENSE00003488163	117988382	117988502
ENSE00003520881	117993999	117994149
ENSE00003547064	117993241	117993410
ENSE00003550134	117995589	117995710
ENSE00003598467	117989442	117989620
ENSE00003900215	117986394	117986534

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.03.

FANTOM5 (CAGE): breadth broad, TPM avg 55.2890 / max 1456.0927, expressed in 647 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116954	55.2890	647

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.03	gold quality
leukocyte	CL:0000738	97.99	gold quality
mononuclear cell	CL:0000842	97.93	gold quality
monocyte	CL:0000576	97.92	gold quality
blood	UBERON:0000178	96.53	gold quality
spleen	UBERON:0002106	96.26	gold quality
bone marrow cell	CL:0002092	94.66	gold quality
lymph node	UBERON:0000029	94.34	gold quality
vermiform appendix	UBERON:0001154	94.23	gold quality
gall bladder	UBERON:0002110	92.94	gold quality
rectum	UBERON:0001052	89.69	gold quality
right coronary artery	UBERON:0001625	89.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.24	gold quality
bone marrow	UBERON:0002371	89.00	gold quality
colonic epithelium	UBERON:0000397	88.62	gold quality
upper lobe of left lung	UBERON:0008952	88.25	gold quality
right lung	UBERON:0002167	88.04	gold quality
caecum	UBERON:0001153	87.90	gold quality
upper lobe of lung	UBERON:0008948	87.25	gold quality
small intestine	UBERON:0002108	87.11	gold quality
omental fat pad	UBERON:0010414	85.68	gold quality
bone element	UBERON:0001474	85.62	gold quality
peritoneum	UBERON:0002358	85.60	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.45	gold quality
parietal pleura	UBERON:0002400	84.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.14	gold quality
layer of synovial tissue	UBERON:0007616	84.05	gold quality
superficial temporal artery	UBERON:0001614	83.86	gold quality
mucosa of stomach	UBERON:0001199	83.78	gold quality
lung	UBERON:0002048	83.71	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	459.09
E-CURD-122	yes	33.46
E-ANND-3	yes	22.73
E-CURD-112	yes	14.81
E-MTAB-7303	no	76.90
E-CURD-120	no	44.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, IRF6

miRNA regulators (miRDB)

83 targeting IL10RA, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6126	99.62	68.09	996

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The capacity of neutrophils to respond to IL-10, as assessed by Stat3 tyrosine phosphorylation, SOCS-3 expression, and modulation of cytokine production, is dependent on the level of expression of IL-10R1. (PMID:11490020)
• cmvIL-10 forms a disulfide-linked homodimer that binds two sIL-10R1 molecules. (PMID:12093920)
• IL-10 receptor stimulated the rapid translocation of IL-10E1 to the cell nucleus and the activation of TIMP-1 expression in primary human prostate tumor cell lines. (PMID:12496489)
• Abnormal interleukin 10Ralpha expression contributes to the maintenance of elevated cyclooxygenase-2 in non-small cell lung cancer cells. (PMID:12591723)
• This investigation reveals three previously unrecognized polymorphisms of IL-10R1 (SNP3, SNP4, and SNP5), two of which result in an amino acid substitution; substitution in S138G variant may interfere with binding of IL-10 to IL-10R1. (PMID:12759436)
• Homozygosity of the IL-10R1 G330R allele is associated with schizophrenia and may contribute to the expression of disease phenotype in susceptible individuals. (PMID:17066477)
• polymorphisms of interleukin-10 and its receptor have roles in lung function in COPD (PMID:17331973)
• Genetic variation in IL-10RA/IL-22 genes may play a modulatory role in the outcome of hepatitis C infection. (PMID:17845543)
• The IL-4R Ile50/Ile50 and IL-10R2 G520/G520 and G520/A520 genotypes were shown to determine the susceptibility to SLE (systemic lupus erythematosus)in a Chinese population (PMID:17988330)
• The peripheral blood neutrophils of septic patients constitutively display abundant levels of surface IL-10R1. (PMID:18308712)
• IL-10R is associated with the progression of the renal cell carcinoma (PMID:18344594)
• Data demonstrate a significant relation between cervical concentrations of IL-10 and single nucleotide polymorphisms in the IL-10 receptor alpha and beta genes. (PMID:18674658)
• The IL-10R1 S138G loss-of-function allele and ulcerative colitis are reported. (PMID:18800073)
• a variant rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p = 0.01) and genotype (p = 3.34x10(-4)) may have a role in preterm birth (PMID:18818748)
• IL-10R1 variants differentially reduce the signaling activity of cmvIL-10 (PMID:19016528)
• G carriers for the -536AG IL-10R1 gene polymorphism had higher systolic and diastolic pressures, and IL-10 levels; and obese G carriers had an increased waist-to-hip ratio. (PMID:19798061)
• Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. (PMID:19890111)
• in the Lebanese population, the loss-of-function allele IL-10R1-S138G (SNP3) is unlikely to provide a protective effect against ulcerative colitis and that both IL-10R1 variants do not correlate with inflammatory bowel disease (PMID:20186944)
• The IL-10RA gene SNP S138G may contribute to susceptibility to atopic diseases but serum IL-10 level is not a sensitive indicator in atopy. (PMID:20232770)
• Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART. (PMID:21396623)
• linkage disequilibrium (LD) blocks were formed in IL10 and IL10RA (PMID:21532858)
• IL-10R1 S138G loss-of-function polymorphism is associated with extrapulmonary tuberculosis risk development in Tunisia. (PMID:21553229)
• IL-10R1 expression on CD4+ T cells and signalling in PBMCs were down-regulated in lupus nephritis (LN) patients, indicating that IL-10 and its receptor may have a special role in LN pathogenesis (PMID:21635228)
• IL10R1-G330R does not alter surface expression but duration of STAT phosphorylation, indicating that the position of G330 is important in stabilizing the STAT signal. (PMID:21654841)
• The haplotype -185/-116 of IL10 receptor alpha in combination with the haplotype -754/-750 of IL10 receptor beta contributed towards mild malaria. (PMID:21814839)
• IL-10R1 is a novel substrate of betaTrCP-containing ubiquitin E3 ligase, a novel negative regulatory mechanism that may potentially affect IL-10 function (PMID:22087322)
• We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. (PMID:22155628)
• Of 66 patients with infantile (very early onset) inflammatory bowel disease, 16 had IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. (PMID:22549091)
• IL10RA polymorphisms are associated with ulcerative colitis. (PMID:22550014)
• The results suggest that genetic polymorphisms in TNF and IL10RA genes may modify the association between blood transfusion and NHL risk. (PMID:22649007)
• In the Chinese Han population, missense SNPs within the exons of the IL-10R1 gene do not contribute to the development of systemic lupus erythematosus (PMID:22652629)
• Single nucleotide polymorphisms in the IL10, IL10RA, and IL10RB genes may contribute to hypertension in the risk of ischemic stroke in the Korean population. (PMID:23096091)
• The dynamic genome-wide transcriptional responses were nearly identical at early time points following stimulation (when STAT3 is active in response to both IL-6 and IL-10) but divergent at later times (when STAT3 is active only in response to IL-10). (PMID:23166328)
• A mutation in TLR4 (rs4986790) and IL10RA (rs22291130) was significantly associated with Mycobacterium avium subspecies paratuberculosis-positive Crohn’s disease patients. (PMID:23455702)
• This report confirms the genetic defect of IL-10RA in neonatal-onset inflammatory bowel disease. (PMID:23839161)
• 5 patients with an IL-10R1 or IL-10R2 deficiency developed B-cell non-Hodgkin lymphoma between the ages of 5 and 6 years (which was recurrent in 1 patient). (PMID:24089328)
• Mutations in the IL10RA gene is associated with ulcerative colitis. (PMID:24216686)
• IFN-gamma selectively induced the expression of IL-10R1 on intestinal epithelia, predominantly on the apical membrane of polarized epithelial cells. (PMID:24367025)
• Case Report: pediatric ulcerative colitis with a novel point mutation within the IL10RA promoter (the -413G->T), inherited from his mother. (PMID:24379584)
• Very early onset inflammatory bowel disease associated with aberrant trafficking of IL-10R1 and cure by T cell replete haploidentical bone marrow transplantation. (PMID:24519095)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	il22ra2	ENSDARG00000039439
danio_rerio	ifngr2	ENSDARG00000067795
danio_rerio	ifngr1l	ENSDARG00000074488
danio_rerio	ifngr1	ENSDARG00000074771
danio_rerio	crfb16	ENSDARG00000075181
danio_rerio	ifnlr1	ENSDARG00000087131
danio_rerio	crfb15	ENSDARG00000099342
mus_musculus	Il10ra	ENSMUSG00000032089
rattus_norvegicus	Il10ra	ENSRNOG00000016308

Paralogs (11): IL20RA (ENSG00000016402), IFNGR1 (ENSG00000027697), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Interleukin-10 receptor subunit alpha — Q13651 (reviewed: Q13651)

Alternative names: CDw210a, Interleukin-10 receptor subunit 1

All UniProt accessions (3): Q13651, E9PKU2, E9PPU4

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a conformational change in IL10RB, allowing IL10RB to bind IL10 as well. In turn, the heterotetrameric assembly complex, composed of two subunits of IL10RA and IL10RB, activates the kinases JAK1 and TYK2 that are constitutively associated with IL10RA and IL10RB respectively. These kinases then phosphorylate specific tyrosine residues in the intracellular domain in IL10RA leading to the recruitment and subsequent phosphorylation of STAT3. Once phosphorylated, STAT3 homodimerizes, translocates to the nucleus and activates the expression of anti-inflammatory genes. In addition, IL10RA-mediated activation of STAT3 inhibits starvation-induced autophagy.

Subunit / interactions. Interacts with IL10. Interacts with IL10RB. Interacts (via its cytoplasmic domain) with JAK1 (via N-terminus). Interacts with BTRC; this interaction leads to IL10RA ubiquitination and subsequent degradation. Interacts with STAT3. (Microbial infection) Interacts with human cytomegalovirus protein IL10. (Microbial infection) Interacts with Epstein-Barr virus protein IL10.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Primarily expressed in hematopoetic cells including B-cells, T-cells, NK cells, monocytes and macrophages. Not expressed in non-hematopoetic cells such as fibroblasts or endothelial cells.

Post-translational modifications. Phosphorylated. Phosphorylation of the cytoplasmic tail induced STAT3 activation. Ubiquitinated by BTRC; ubiquitination leads to endocytosis and subsequent degradation of IL10RA.

Disease relevance. Inflammatory bowel disease 28, autosomal recessive (IBD28) [MIM:613148] A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the type II cytokine receptor family.

RefSeq proteins (1): NP_001549* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108

UniProt features (52 total): sequence variant 15, strand 14, glycosylation site 6, helix 5, compositionally biased region 3, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1Y6K	X-RAY DIFFRACTION	2.52
5IXI	X-RAY DIFFRACTION	2.57
1LQS	X-RAY DIFFRACTION	2.7
1Y6N	X-RAY DIFFRACTION	2.7
1Y6M	X-RAY DIFFRACTION	2.8
1J7V	X-RAY DIFFRACTION	2.9
6X93	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13651-F1	63.05	0.35

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 (2): 56–75, 202–223

Glycosylation sites (6): 50, 74, 110, 154, 177, 189

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6783783	Interleukin-10 signaling
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer

MSigDB gene sets: 476 (showing top): GOBP_DIGESTION, GOBP_REGULATION_OF_AUTOPHAGY, WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOLDRATH_IMMUNE_MEMORY, MODULE_45, MODULE_64, HASLINGER_B_CLL_WITH_MUTATED_VH_GENES, MORI_IMMATURE_B_LYMPHOCYTE_UP, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (9): negative regulation of autophagy (GO:0010507), cytokine-mediated signaling pathway (GO:0019221), response to lipopolysaccharide (GO:0032496), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), negative regulation of inflammatory response (GO:0050728), regulation of synapse organization (GO:0050807), intestinal epithelial structure maintenance (GO:0060729), ubiquitin-dependent endocytosis (GO:0070086), interleukin-10-mediated signaling pathway (GO:0140105)

GO Molecular Function (4): interleukin-10 receptor activity (GO:0004920), interleukin-10 binding (GO:0019969), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), apical plasma membrane (GO:0016324), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
Signaling by ALK fusions and activated point mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
maintenance of gastrointestinal epithelium	1
endocytosis	1
protein transport	1
protein localization to organelle	1
establishment of protein localization to organelle	1
cytokine-mediated signaling pathway	1
cytokine receptor activity	1
interleukin-10 binding	1
growth factor binding	1
cytokine binding	1
molecular transducer activity	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
apical part of cell	1
plasma membrane region	1

Protein interactions and networks

STRING

2335 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL10RA	IL10RB	Q08334	999
IL10RA	IL10	P22301	998
IL10RA	JAK1	P23458	987
IL10RA	IL22RA1	Q8N6P7	971
IL10RA	TYK2	P29597	970
IL10RA	STAT3	P40763	967
IL10RA	IFNLR1	Q8IU57	930
IL10RA	IL20RB	Q6UXL0	910
IL10RA	IL6	P05231	868
IL10RA	STAT1	P42224	841
IL10RA	STAT5A	P42229	839
IL10RA	TNF	P01375	837
IL10RA	IL22	Q9GZX6	832
IL10RA	IFNL3	Q8IZI9	812
IL10RA	IL26	Q9NPH9	807

IntAct

97 interactions, top by confidence:

A	B	Type	Score
IL10	IL10RA	psi-mi:“MI:0407”(direct interaction)	0.860
IL10RA	IL10	psi-mi:“MI:0407”(direct interaction)	0.860
IL10	IL10RA	psi-mi:“MI:0414”(enzymatic reaction)	0.860
IL10RA	BTRC	psi-mi:“MI:0915”(physical association)	0.680
BTRC	IL10RA	psi-mi:“MI:0915”(physical association)	0.680
	IL10RA	psi-mi:“MI:0407”(direct interaction)	0.650
IL10RA	UL111A	psi-mi:“MI:0407”(direct interaction)	0.620
IL10	IL10RB	psi-mi:“MI:0915”(physical association)	0.590
HACD2	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
GYPA	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
SLC30A2	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
TMEM60	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
CD302	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
VAMP5	IL10RA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (30): IL10RA (Two-hybrid), IL10RA (Two-hybrid), IL10RA (Two-hybrid), SELK (Two-hybrid), PQLC1 (Two-hybrid), C16orf58 (Two-hybrid), CMTM3 (Two-hybrid), PTPLA (Two-hybrid), SMCO4 (Two-hybrid), BTRC (Two-hybrid), TMUB2 (Two-hybrid), MAL (Two-hybrid), NIPAL4 (Two-hybrid), YIPF6 (Two-hybrid), C1QL4 (Two-hybrid)

ESM2 similar proteins: A0A1B0GU29, A6NLX4, A6QNY1, A9CBA0, B7ZWI3, O14669, O88472, P14784, P16297, P25918, P26896, Q0VFL4, Q13651, Q32M26, Q38J84, Q38J85, Q3SYS8, Q58CT8, Q5BK39, Q5EAA5, Q5HZE8, Q5NCP0, Q5RCL0, Q64322, Q68DV7, Q6AXS2, Q6AXU5, Q6NUJ2, Q6UWV7, Q86UW2, Q8BHB3, Q8BLR5, Q8BSU2, Q8C353, Q8C708, Q8K1T1, Q8MII8, Q8N6P7, Q8NET5, Q8R182

Diamond homologs: Q13651, Q61727, Q7TNI4, Q80XF5

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
IL10	“up-regulates activity”	IL10RA	binding
IL10RA	“up-regulates activity”	JAK2	phosphorylation
IL10RA	“up-regulates activity”	JAK1
IL10	up-regulates	IL10RA	binding
IL10RA	“up-regulates activity”	JAK1	binding
JAK1	“up-regulates activity”	IL10RA	phosphorylation
IL10RA	up-regulates	Phagocytosis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	4
Uncertain significance	223
Likely benign	175
Benign	21

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1074445	NM_001558.4(IL10RA):c.756C>A (p.Tyr252Ter)	Pathogenic
1435397	NM_001558.4(IL10RA):c.618dup (p.Pro207fs)	Pathogenic
1478637	NM_001558.4(IL10RA):c.769C>T (p.Gln257Ter)	Pathogenic
14814	NM_001558.4(IL10RA):c.421G>A (p.Gly141Arg)	Pathogenic
14815	NM_001558.4(IL10RA):c.251C>T (p.Thr84Ile)	Pathogenic
1978943	NM_001558.4(IL10RA):c.258_279dup (p.Asn94fs)	Pathogenic
2022922	NM_001558.4(IL10RA):c.439_452del (p.Arg147fs)	Pathogenic
2137257	NM_001558.4(IL10RA):c.470A>G (p.Tyr157Cys)	Pathogenic
2729159	NM_001558.4(IL10RA):c.501T>G (p.Tyr167Ter)	Pathogenic
2751753	NM_001558.4(IL10RA):c.349C>T (p.Arg117Cys)	Pathogenic
3656591	NM_001558.4(IL10RA):c.3G>A (p.Met1Ile)	Pathogenic
3721097	NM_001558.4(IL10RA):c.99G>A (p.Trp33Ter)	Pathogenic
39430	NM_001558.4(IL10RA):c.784C>T (p.Arg262Cys)	Pathogenic
830052	NM_001558.4(IL10RA):c.634C>T (p.Arg212Ter)	Pathogenic
943905	NM_001558.4(IL10RA):c.506T>C (p.Ile169Thr)	Pathogenic
1471309	NM_001558.4(IL10RA):c.68-1G>A	Likely pathogenic
4846816	NM_001558.4(IL10RA):c.127del (p.Leu43fs)	Likely pathogenic
4849293	NM_001558.4(IL10RA):c.67+1G>A	Likely pathogenic
802794	NM_001558.4(IL10RA):c.787C>T (p.Arg263Ter)	Likely pathogenic

SpliceAI

1042 predictions. Top by Δscore:

Variant	Effect	Δscore
11:117993240:GT:G	acceptor_gain	1.0000
11:117993997:A:AG	acceptor_gain	1.0000
11:117993998:G:GG	acceptor_gain	1.0000
11:117994145:G:GT	donor_gain	1.0000
11:117994145:GCAGT:G	donor_gain	1.0000
11:117994148:GT:G	donor_gain	1.0000
11:117994150:G:GG	donor_gain	1.0000
11:117995578:T:TA	acceptor_gain	1.0000
11:117995711:G:GG	donor_gain	1.0000
11:117995712:T:G	donor_loss	1.0000
11:117998711:CCAGC:C	acceptor_loss	1.0000
11:117998712:CAGCT:C	acceptor_loss	1.0000
11:117998713:A:AG	acceptor_gain	1.0000
11:117998713:AGCT:A	acceptor_loss	1.0000
11:117998714:G:GG	acceptor_gain	1.0000
11:117998714:GC:G	acceptor_gain	1.0000
11:117998714:GCT:G	acceptor_gain	1.0000
11:117998714:GCTC:G	acceptor_gain	1.0000
11:117988380:AG:A	acceptor_gain	0.9900
11:117988381:GG:G	acceptor_gain	0.9900
11:117988468:TCTGA:T	donor_gain	0.9900
11:117988498:CTGAG:C	donor_loss	0.9900
11:117988500:GAGGT:G	donor_loss	0.9900
11:117988501:AGG:A	donor_loss	0.9900
11:117988502:GGTGA:G	donor_loss	0.9900
11:117988503:GTGAG:G	donor_loss	0.9900
11:117988504:T:A	donor_loss	0.9900
11:117989438:TCAG:T	acceptor_loss	0.9900
11:117989441:G:GA	acceptor_loss	0.9900
11:117989441:GGT:G	acceptor_gain	0.9900

AlphaMissense

3786 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:117989555:G:C	R101P	0.991
11:117988447:T:A	W45R	0.990
11:117988447:T:C	W45R	0.990
11:117989584:T:A	W111R	0.989
11:117989584:T:C	W111R	0.989
11:117988414:T:C	F34L	0.986
11:117988416:T:A	F34L	0.986
11:117988416:T:G	F34L	0.986
11:117989586:G:C	W111C	0.985
11:117989586:G:T	W111C	0.985
11:117989606:T:C	F118S	0.985
11:117988449:G:C	W45C	0.984
11:117988449:G:T	W45C	0.984
11:117988442:T:A	L43H	0.983
11:117988415:T:C	F34S	0.981
11:117994069:T:A	V203D	0.981
11:117993354:T:C	F161L	0.977
11:117993356:C:A	F161L	0.977
11:117993356:C:G	F161L	0.977
11:117989546:C:A	A98D	0.975
11:117988415:T:G	F34C	0.974
11:117989539:T:G	Y96D	0.972
11:117993301:T:C	I143T	0.972
11:117989579:C:T	S109F	0.971
11:117994029:T:C	F190L	0.971
11:117994031:C:A	F190L	0.971
11:117994031:C:G	F190L	0.971
11:117989458:T:A	W69R	0.970
11:117989458:T:C	W69R	0.970
11:117994065:T:A	C202S	0.970

dbSNP variants (sampled 300 via entrez): RS1000070267 (11:117985052 G>A), RS1000229980 (11:117994234 G>A), RS1000394213 (11:117987958 A>G), RS1000578410 (11:117994571 A>G), RS1000683678 (11:117994644 T>C), RS1000802262 (11:117990165 C>T), RS1000964535 (11:117992705 C>T), RS1001178060 (11:117986588 A>C,G,T), RS1001414207 (11:118000083 C>T), RS1001512453 (11:117988070 T>C), RS1001640771 (11:117990925 G>A), RS1001641101 (11:117984801 G>A), RS1001849491 (11:117986643 G>A,T), RS1001904088 (11:117988978 C>T), RS1001968757 (11:117990572 A>G)

Disease associations

OMIM: gene MIM:146933 | disease phenotypes: MIM:613148

GenCC curated gene-disease

Disease	Classification	Inheritance
inflammatory bowel disease 28	Strong	Autosomal recessive
IL10-related early-onset inflammatory bowel disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
inflammatory bowel disease 28	Definitive	AR

Mondo (2): inflammatory bowel disease 28 (MONDO:0013153), IL10-related early-onset inflammatory bowel disease (MONDO:0016542)

Orphanet (1): Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome (Orphanet:238569)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000155	Oral ulcer
HP:0000999	Pyoderma
HP:0001510	Growth delay
HP:0002573	Hematochezia
HP:0002583	Colitis
HP:0004387	Enterocolitis
HP:0009789	Perianal abscess
HP:0025084	Folliculitis
HP:0100280	Crohn’s disease

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_794	Obesity-related traits	6.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567728	Inflammatory Bowel Disease 28, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4804254 (PROTEIN COMPLEX)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — IL-10 receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
IL-10	Agonist	10.3	pEC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, increases expression, decreases expression	2
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	2
Mustard Gas	decreases expression, increases secretion	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
4-oxoretinoic acid	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
pentanal	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
abrine	increases expression	1
teriflunomide	increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fluvastatin	increases expression, affects cotreatment	1
Alitretinoin	decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzene	increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Benzoates	decreases expression	1
Cisplatin	increases expression	1
Demecolcine	increases expression	1
Dietary Carbohydrates	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Diuron	decreases expression	1

Cellosaurus cell lines

5 cell lines: 2 induced pluripotent stem cell, 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4XU	SDQLCHi040-A	Induced pluripotent stem cell	Female
CVCL_A8CF	HEK-Blue IL-10	Transformed cell line	Female
CVCL_D8N0	Ubigene HCT 116 IL10RA KO	Cancer cell line	Male
CVCL_E6U4	Genomeditech HEK-293 H_IL10 Reporter	Transformed cell line	Female
CVCL_XV11	SDQLCHi012-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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