IL10RB
protein-codinginterleukin 10 receptor subunit beta, the group of CD molecules|Interleukin receptors
Gene summary
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. [provided by RefSeq, Jul 2008]
- CRFB4
- D21S58
- D21S66
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012941
Submitter: ClinGen
The IL10RB gene encodes for IL10Rβ. IL10Rβ is the signaling subunit of the IL10R complex that binds IL10. IL10 signaling functions as an anti-inflammatory pathway that can inhibit proinflammatory responses of both innate and adaptive immune cells. Inflammatory bowel disease 25, early onset, autosomal recessive presents as very early onset IBD. A total of 10 variants, including nonsense and missense, have been reported in 5 patients in 3 publications (PMID: 28267044, 23158016, 19890111). Variants were found to be inherited in an autosomal recessive manner, variants segregate with disease, and the disease mechanism is suggested to be loss of function. Experimental evidence includes reduction of IL10RB expression and IL10 signaling in the patients’ cells and loss of Il-10 response in LPS stimulated PBMCs. Mice with IL10/IL10 receptor deficiency recapitulate the severe intestinal inflammation and cellular phenotypes seen in patients with IL10RB deficiency. Reports included in the curation span the time period from 2009 until present, therefore the classification is definitive.
Inheritance Pattern: AR
Disease ID:MONDO:0012941
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016542
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012941
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Gastrointestinal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: HSCT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IL10RB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000628.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 70 | 1 | 73 | ||
| missense | 102 | 13 | 115 | |||
| nonsense | 8 | 1 | 1 | 10 | ||
| start loss | 2 | 2 | ||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 7 | 5 | 13 | ||
| Total | 9 | 9 | 114 | 83 | 1 | 216 |
Highest pathogenic variant AF is 0.000014250398
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000619.3 | 7 | MANE Select | |
| Ensembl | ENSP00000290200.2 | 7 | MANE Select | |
| RefSeq | NP_001392778.1 | 7 | Standard | |
| RefSeq | NP_001392779.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| il10rb | Danio rerio | Structure: liver Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Jak-STAT signaling pathway - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
- Toxoplasmosis - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- Epstein-Barr virus infection - Homo sapiens (human)
Biological Process
- inflammatory response
- immune response
- signal transduction
- cytokine-mediated signaling pathway
- defense response to virus
Molecular Function
- cytokine receptor activity
- interleukin-10 receptor activity
- protein binding
- signaling receptor activity
Cellular Component
- plasma membrane
- integral component of membrane
- interleukin-28 receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000290200
- Coding exons
- 7
- Length
- 30877
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 24
- Defined
- 125748
- p
- 0.0000954
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.645 | 148 | 172 | 0.862 | 0.00000949 | 2158 |
| Missense (PolyPhen) | 24 | 38.826 | 0.61815 | 564 | ||
| Synonymous | 0.179 | 66 | 67.9 | 0.972 | 0.00000437 | 597 |
| Loss of Function | 1.22 | 11 | 16.3 | 0.674 | 7.76e-7 | 183 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:12469119, ECO:0000269|PubMed:15123776}.;
- Disease
- DISEASE: Inflammatory bowel disease 25 (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. {ECO:0000269|PubMed:19890111}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.213
Intolerance Scores
- LoFtool
- 0.558
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.865
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |