IL10RB

Summary

IL10RB (interleukin 10 receptor subunit beta, HGNC:5965) is a protein-coding gene on chromosome 21q22.11, encoding Interleukin-10 receptor subunit beta (Q08334). Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1.

The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21.

Source: NCBI Gene 3588 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inflammatory bowel disease 25 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 100 total — 6 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_000628

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5965
Approved symbol	IL10RB
Name	interleukin 10 receptor subunit beta
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	CRF2-4, CDW210B, IL-10R2
Ensembl gene	ENSG00000243646
Ensembl biotype	protein_coding
OMIM	123889
Entrez	3588

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000290200, ENST00000422891, ENST00000451065, ENST00000493295, ENST00000498371, ENST00000609556, ENST00000637650, ENST00000696764, ENST00000696765, ENST00000896210, ENST00000896211, ENST00000896212, ENST00000896213

RefSeq mRNA: 4 — MANE Select: NM_000628 NM_000628, NM_001405849, NM_001405850, NM_001406840

CCDS: CCDS13623

Canonical transcript exons

ENST00000290200 — 7 exons

Exon	Start	End
ENSE00001043281	33266367	33266514
ENSE00001927323	33296184	33297221
ENSE00003490674	33276596	33276753
ENSE00003519873	33279752	33279918
ENSE00003554973	33268394	33268517
ENSE00003620117	33283094	33283241
ENSE00003628210	33288104	33288261

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.1355 / max 382.3874, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188843	33.6003	1813
188844	1.3365	645
188846	0.0747	18
188842	0.0699	37
188845	0.0542	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	96.49	gold quality
monocyte	CL:0000576	96.25	gold quality
leukocyte	CL:0000738	96.23	gold quality
blood	UBERON:0000178	96.12	gold quality
granulocyte	CL:0000094	95.21	gold quality
mucosa of transverse colon	UBERON:0004991	94.21	gold quality
rectum	UBERON:0001052	93.64	gold quality
spleen	UBERON:0002106	93.62	gold quality
duodenum	UBERON:0002114	93.04	gold quality
vermiform appendix	UBERON:0001154	92.61	gold quality
gall bladder	UBERON:0002110	91.11	gold quality
transverse colon	UBERON:0001157	90.99	gold quality
stromal cell of endometrium	CL:0002255	90.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.81	gold quality
lymph node	UBERON:0000029	90.77	gold quality
small intestine	UBERON:0002108	90.46	gold quality
body of pancreas	UBERON:0001150	90.35	gold quality
esophagus mucosa	UBERON:0002469	90.18	gold quality
islet of Langerhans	UBERON:0000006	90.07	gold quality
omental fat pad	UBERON:0010414	89.96	gold quality
pancreas	UBERON:0001264	89.91	gold quality
right lung	UBERON:0002167	89.59	gold quality
upper lobe of left lung	UBERON:0008952	89.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.48	gold quality
body of stomach	UBERON:0001161	89.40	gold quality
intestine	UBERON:0000160	89.33	gold quality
adipose tissue	UBERON:0001013	89.08	gold quality
smooth muscle tissue	UBERON:0001135	89.08	gold quality
fallopian tube	UBERON:0003889	88.98	gold quality
bone marrow cell	CL:0002092	88.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting IL10RB, 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-5193	100.00	67.26	1744
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-1245A	96.33	66.25	498
HSA-MIR-6851-3P	95.73	65.11	688
HSA-MIR-6514-5P	95.07	66.02	655

Literature-anchored findings (GeneRIF, showing 40)

• distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2) (PMID:12483210)
• sensitivity to recombinant interleukin-26(IL-26) of various cell lines strictly correlated with the expression of IL-20 receptor 1 and blocking antibodies against either IL-10 receptor 2 or IL-20 receptor 1 inhibited IL-26-dependent signal transduction (PMID:15178681)
• model of the ternary complex of interleukin-10 with its soluble receptors (PMID:15985167)
• data suggest that despite normal levels of IL-10R expression, and an apparent lack of abnormalities in intracellular signals induced through this receptor, immune cells from SLE patients exhibit aberrant pattern of gene expression induced through IL-10R (PMID:17062437)
• These findings suggested that signaling through IL-10R2 may play a causative role in dcSSc. (PMID:18588853)
• 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-22R and IL-10R2 binding sites are juxtaposed on adjacent IL-22 surfaces contributed mostly by helices A, D, and F and loop AB. (PMID:18675824)
• gene polymorphism in combination with IL-10 gene polymorphism is assiociated with GvHD in HLA-identical donor-recipient pairs (PMID:19409109)
• Inhibition of S100A11 gene expression impairs the ability of keratinocytes to control vaccinia virus replication via downregulation of IFN-lambda receptor IL-10R2. (PMID:19577285)
• The association with the susceptibility to HBV infection was only observed for IL10RB K47E when we compared the individuals with persistent HBV infection through nonmaternal transmission to the controls with asymptomatic self-limited HBV infection. (PMID:19714778)
• 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)
• It is concluded that there is a strong association between the IL10 and IL10RB SNPs, and BPH in Korean population (PMID:21532858)
• 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)
• 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)
• IL10RB polymorphisms are associated with Crohn’s disease. (PMID:22550014)
• 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 effects of two functional polymorphisms, type I interferon receptor 2 gene (IFNAR2)-F8S and interleukin-10 receptor subunit beta gene (IL10RB)-K47E, on chronic hepatitis B virus (HBV) infection, were investigated. (PMID:23745570)
• IL-10RB rs2834167 (A/G) polymorphism may be a potential biomarker for susceptibility to systemic lupus erythematosus. (PMID:23749100)
• 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)
• Results show that the distribution of IL10RB and IL28RA genotypes among the Hepatitis C virus-infected and control groups did not differ significantly. (PMID:24144988)
• Mutations in the IL10RB gene is associated with ulcerative colitis. (PMID:24216686)
• Case Report: pediatric ulcerative colitis patient compound heterozygote for the IL10RB E47K polymorphism, inherited from his father. (PMID:24379584)
• No evidence for an involvement of autoantibodies against IL-10 or IL-10R in the pathogenesis of inflammatory bowel disease could be established. (PMID:24581234)
• Inflammatory bowel disease (IBD) in infancy is phenotypically and genetically different disease entity from adult-onset or older child-onset IBD. It has a strong association with IL-10 receptor gene. (PMID:24785691)
• PAPL, IL10RB and DEPDC5 polymorphisms have an impact on progression of hepatitis B virus-related liver disease. (PMID:25032264)
• genetic association study in cohort of infants/children: Data suggest perianal fistulas are exhibited in patients with very early-onset inflammatory bowel disease with IL10 receptor mutations (IL10RA/B); prognosis and response to treatment are poor. (PMID:25373860)
• High IL10RB expression is associated with diffuse large B-cell lymphoma. (PMID:25733167)
• IL10R2 Overexpression promotes IL22/STAT3 signaling in colorectal carcinogenesis. (PMID:26130064)
• IL-10 and IL-10R gene polymorphisms may not contribute to the susceptibility to MM but may be associated with the severity and prognosis of MM. In particular, IL-10RB K47E polymorphism may contribute to the poor prognosis of MM patients treated with thalidomide and/or bortezomib. (PMID:27405747)
• systemic mRNA expression of IL10RB strongly differentiated children who failed to achieve asthma control with triamcinolone administration (PMID:27665382)
• We identified 32 compound heterozygous mutations and 9 homozygous mutations in IL10 receptor subunit alpha and 1 homozygous mutation in IL10 receptor subunit beta. Among these mutations, 10 novel mutations were identified, and 6 pathogenic mutations had been previously described. In patients with IL10 receptor subunit alpha mutations, c.301C>T (p.R101RW) and c.537 G>A (p.T179T) were the most common mutations. (PMID:28267044)
• Expression of IL10R subunits within the leukocyte population (CD45(+) cells) was significantly higher in primary brain tumors than in metastases. (PMID:28982901)
• IFN-lambda4 suppressed HIV infection of macrophages. This IFN-lambda4-mediated HIV inhibition was compromised by the antibodies against IFN-lambda receptor complex, IFN-lambdaR1/IL-10R2. (PMID:30247785)
• analysis of two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling (PMID:30365510)
• Synthetic interleukin 22 (IL-22) signaling reveals biological activity of homodimeric IL-10 receptor 2 and functional cross-talk with the IL-6 receptor gp130. (PMID:32611765)
• Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes. (PMID:33260695)
• IL-10 receptor expression on lymphocytes and monocytes in children with food allergy. (PMID:33595140)
• Integrative genomics analysis reveals a 21q22.11 locus contributing risk to COVID-19. (PMID:33949668)
• Association of Interleukin Genes IL10 and IL10RB with Parameters of Overweight in Military Students. (PMID:35205336)
• Regulation of the Human IL-10RB Gene Expression by Sp8 and Sp9. (PMID:35811529)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	crfb4	ENSDARG00000068711
mus_musculus	Il10rb	ENSMUSG00000022969
rattus_norvegicus	Il10rb	ENSRNOG00000028638

Paralogs (11): IL20RA (ENSG00000016402), IFNGR1 (ENSG00000027697), IL10RA (ENSG00000110324), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436)

Protein

Protein identifiers

Interleukin-10 receptor subunit beta — Q08334 (reviewed: Q08334)

Alternative names: Cytokine receptor class-II member 4, Cytokine receptor family 2 member 4, Interleukin-10 receptor subunit 2

All UniProt accessions (5): Q08334, A0A1B0GTI5, A0A1B0GU52, F8WDX2, H7C0Z5

UniProt curated annotations — full annotation on UniProt →

Function. Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state.

Subunit / interactions. Heterodimer with IFNLR1.

Subcellular location. Membrane.

Disease relevance. Inflammatory bowel disease 25, autosomal recessive (IBD25) [MIM:612567] 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.

Polymorphism. Genetic variations in IL10RB influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424].

Similarity. Belongs to the type II cytokine receptor family.

RefSeq proteins (4): NP_000619, NP_001392778, NP_001392779, NP_001393769 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015373	Interferon/interleukin_rcp_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108, PF09294

UniProt features (44 total): strand 19, glycosylation site 4, sequence conflict 4, helix 3, disulfide bond 2, topological domain 2, turn 2, domain 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3LQM	X-RAY DIFFRACTION	2.14
5T5W	X-RAY DIFFRACTION	2.85
9BPV	ELECTRON MICROSCOPY	3
9BPU	ELECTRON MICROSCOPY	3.26
6X93	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08334-F1	82.83	0.65

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): 66–74, 188–209

Glycosylation sites (4): 68, 102, 161, 49

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-449836	Other interleukin signaling
R-HSA-6783783	Interleukin-10 signaling
R-HSA-8854691	Interleukin-20 family signaling

MSigDB gene sets: 299 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, JI_RESPONSE_TO_FSH_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOLDRATH_IMMUNE_MEMORY, KYNG_DNA_DAMAGE_DN, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (10): inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), cytokine-mediated signaling pathway (GO:0019221), type III interferon-mediated signaling pathway (GO:0038196), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), defense response to virus (GO:0051607), cellular response to virus (GO:0098586), interleukin-10-mediated signaling pathway (GO:0140105), positive regulation of cellular respiration (GO:1901857)

GO Molecular Function (4): interleukin-10 receptor activity (GO:0004920), coreceptor activity (GO:0015026), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), interleukin-28 receptor complex (GO:0032002)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Interleukins	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
response to virus	2
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cellular response to type III interferon	1
interferon-mediated signaling pathway	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
cytokine-mediated signaling pathway	1
positive regulation of metabolic process	1
regulation of cellular respiration	1
cellular respiration	1
cytokine receptor activity	1
interleukin-10 binding	1
signaling receptor activity	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

1523 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL10RB	IL10RA	Q13651	999
IL10RB	IL22RA1	Q8N6P7	999
IL10RB	IFNLR1	Q8IU57	999
IL10RB	IL10	P22301	997
IL10RB	IL22	Q9GZX6	997
IL10RB	IFNL1	Q8IU54	995
IL10RB	TYK2	P29597	994
IL10RB	IFNL3	Q8IZI9	994
IL10RB	IL26	Q9NPH9	993
IL10RB	IL20RA	Q9UHF4	987
IL10RB	JAK1	P23458	986
IL10RB	IFNL2	Q8IZJ0	982
IL10RB	IFNAR2	P48551	899
IL10RB	STAT3	P40763	865
IL10RB	IL19	Q9UHD0	810

IntAct

16 interactions, top by confidence:

A	B	Type	Score
IL22	IL10RB	psi-mi:“MI:0915”(physical association)	0.590
IL10	IL10RB	psi-mi:“MI:0915”(physical association)	0.590
IL22RA1	IL10RB	psi-mi:“MI:0915”(physical association)	0.400
IL10RB	IL22RA1	psi-mi:“MI:0915”(physical association)	0.400
UL111A	IL10RB	psi-mi:“MI:0915”(physical association)	0.400
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): IL10RB (Affinity Capture-MS), IL10RB (Affinity Capture-MS), IL10RB (Positive Genetic), PIK3CA (Positive Genetic), SRC (Positive Genetic), TNFRSF1A (Positive Genetic), IL10RB (Affinity Capture-RNA), IL10RA (Affinity Capture-Western), IL10RB (Affinity Capture-Western), IL10RB (Affinity Capture-MS), IL10RB (Affinity Capture-Western), ATG16L1 (Affinity Capture-Western), TM9SF3 (Co-fractionation), IL10RB (Affinity Capture-MS), IL10RB (Affinity Capture-RNA)

ESM2 similar proteins: A1A5C7, A5D7H1, A6H7A0, A6NJW4, A6QLN9, A8MUP2, A8MXK1, B0BMW8, B0BNL6, O35393, O62657, O75078, P52875, P55244, P56880, P57791, Q08334, Q0V881, Q15768, Q16557, Q2M1K6, Q3SZQ2, Q3UHH2, Q4V899, Q5E9H2, Q5FYB0, Q5M7U7, Q5R6I6, Q5RCI5, Q5SQ64, Q642A6, Q6PCB0, Q7TPB4, Q8BM89, Q8BZH0, Q8N431, Q8N5I2, Q8R2R5, Q8R2Z5, Q8VE98

Diamond homologs: Q08334, Q61190, Q764M8, Q9UHF4, P17181, P33896, Q04790, Q28589, K9JA28, P15260, Q6PHB0, Q80XF5, Q969J5

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
IL22	up-regulates	IL10RB	binding
IL26	up-regulates	IL10RB	binding
IL10	up-regulates	IL10RB	binding
IL10RB	up-regulates	TYK2	binding
IFNL1	up-regulates	IL10RB	binding
IFNL2	up-regulates	IL10RB	binding
IFNL3	up-regulates	IL10RB	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	2
Uncertain significance	40
Likely benign	39
Benign	7

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2423332	NC_000021.8:g.(?34648881)(34655566_?)del	Pathogenic
2664348	NM_000628.5(IL10RB):c.300G>A (p.Trp100Ter)	Pathogenic
3248153	NC_000021.8:g.(?34638771)(34668662_?)del	Pathogenic
3660494	NM_000628.5(IL10RB):c.168C>G (p.Tyr56Ter)	Pathogenic
41900	NM_000628.5(IL10RB):c.421G>T (p.Glu141Ter)	Pathogenic
831278	NC_000021.9:g.(?33276576)(33276773_?)del	Pathogenic
1066682	NM_000628.5(IL10RB):c.49+2T>G	Likely pathogenic
3728868	NM_000628.5(IL10RB):c.331+1G>A	Likely pathogenic

SpliceAI

1299 predictions. Top by Δscore:

Variant	Effect	Δscore
21:33276754:G:GG	donor_gain	1.0000
21:33279750:A:AG	acceptor_gain	1.0000
21:33279751:G:GG	acceptor_gain	1.0000
21:33279751:GCC:G	acceptor_gain	1.0000
21:33288103:GAAAC:G	acceptor_gain	1.0000
21:33266509:TGTC:T	donor_gain	0.9900
21:33279745:T:A	acceptor_gain	0.9900
21:33279747:CTTA:C	acceptor_loss	0.9900
21:33279749:TA:T	acceptor_loss	0.9900
21:33279750:AG:A	acceptor_loss	0.9900
21:33279751:GCCA:G	acceptor_gain	0.9900
21:33279914:AAAAG:A	donor_loss	0.9900
21:33279916:AAG:A	donor_loss	0.9900
21:33279919:GT:G	donor_loss	0.9900
21:33279920:T:G	donor_loss	0.9900
21:33283092:A:AG	acceptor_gain	0.9900
21:33283093:G:GG	acceptor_gain	0.9900
21:33283093:GTTTC:G	acceptor_gain	0.9900
21:33288098:T:TA	acceptor_gain	0.9900
21:33288102:A:AG	acceptor_gain	0.9900
21:33288103:G:GG	acceptor_gain	0.9900
21:33296182:A:AG	acceptor_gain	0.9900
21:33296183:G:GG	acceptor_gain	0.9900
21:33296231:A:AG	acceptor_gain	0.9900
21:33296232:T:G	acceptor_gain	0.9900
21:33296236:C:A	acceptor_gain	0.9900
21:33266438:G:GT	donor_gain	0.9800
21:33266512:CAG:C	donor_loss	0.9800
21:33266513:AGG:A	donor_loss	0.9800
21:33266514:GGT:G	donor_loss	0.9800

AlphaMissense

2164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:33268464:G:C	W40C	0.997
21:33268464:G:T	W40C	0.997
21:33268462:T:A	W40R	0.996
21:33268462:T:C	W40R	0.996
21:33276688:T:A	V89D	0.993
21:33268443:T:A	N33K	0.992
21:33268443:T:G	N33K	0.992
21:33276722:G:C	W100C	0.992
21:33276722:G:T	W100C	0.992
21:33276735:T:C	F105L	0.991
21:33276737:C:A	F105L	0.991
21:33276737:C:G	F105L	0.991
21:33268457:T:C	L38P	0.990
21:33268436:C:T	S31F	0.989
21:33276720:T:A	W100R	0.986
21:33276720:T:C	W100R	0.986
21:33268463:G:C	W40S	0.985
21:33279874:T:A	W152R	0.985
21:33279874:T:C	W152R	0.985
21:33283157:T:A	C188S	0.983
21:33283158:G:C	C188S	0.983
21:33268452:C:A	N36K	0.982
21:33268452:C:G	N36K	0.982
21:33283154:T:G	Y187D	0.982
21:33268435:T:C	S31P	0.981
21:33276642:T:A	C74S	0.981
21:33276642:T:C	C74R	0.981
21:33276643:G:C	C74S	0.981
21:33283159:T:G	C188W	0.981
21:33268498:T:C	F52L	0.980

dbSNP variants (sampled 300 via entrez): RS1000148905 (21:33277156 T>C), RS1000150452 (21:33286230 G>A), RS1000162135 (21:33286055 C>T), RS1000251675 (21:33265172 T>C), RS1000260932 (21:33283833 A>G), RS1000414284 (21:33289723 C>T), RS1000497015 (21:33287268 G>A), RS1000525004 (21:33268952 C>T), RS1000544524 (21:33270763 C>T), RS1000550068 (21:33289469 G>A), RS1000756507 (21:33283611 T>C,G), RS1000811807 (21:33291275 T>C), RS1000932798 (21:33275307 C>T), RS1001020203 (21:33294875 G>A), RS1001086457 (21:33292621 G>C)

Disease associations

OMIM: gene MIM:123889 | disease phenotypes: MIM:612567, MIM:610424

GenCC curated gene-disease

Disease	Classification	Inheritance
inflammatory bowel disease 25	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 25	Definitive	AR

Mondo (3): inflammatory bowel disease 25 (MONDO:0012941), hepatitis B virus, susceptibility to (MONDO:0012488), IL10-related early-onset inflammatory bowel disease (MONDO:0016542)

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

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000143	Rectovaginal fistula
HP:0002837	Recurrent bronchitis
HP:0003593	Infantile onset
HP:0004387	Enterocolitis
HP:0009789	Perianal abscess
HP:0025084	Folliculitis
HP:0033256	Pancolitis
HP:0033279	Enterocutaneous fistula

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001729_26	Crohn’s disease	2.000000e-16
GCST002260_1	Narcolepsy	2.000000e-08
GCST005522_7	Narcolepsy	5.000000e-06
GCST006585_2770	Blood protein levels	1.000000e-08
GCST009597_125	Multiple sclerosis	8.000000e-06
GCST012399_3	COVID-19	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567251	Inflammatory Bowel Disease 25, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3831284 (PROTEIN COMPLEX), CHEMBL4804251 (PROTEIN COMPLEX), 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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
Acetaminophen	affects cotreatment, increases expression, decreases expression	3
bisphenol A	affects cotreatment, increases expression, decreases methylation	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
Cisplatin	affects expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	decreases methylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
zinc chloride	decreases expression	1
ferrous sulfate	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
1-nitropyrene	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
beta-methylcholine	affects expression	1
tamibarotene	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
ICG 001	increases expression	1
bisphenol S	decreases methylation	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
Decitabine	affects expression	1
Acetylcysteine	decreases expression	1
Air Pollutants, Occupational	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8CF	HEK-Blue IL-10	Transformed cell line	Female
CVCL_A8CG	HEK-Blue IL-22	Transformed cell line	Female
CVCL_E0EU	Ubigene HeLa IL10RB KO	Cancer cell line	Female
CVCL_E6U4	Genomeditech HEK-293 H_IL10 Reporter	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening