IL2RB
Chr 22ARinterleukin 2 receptor subunit beta
Also known as: CD122, IL15RB, IMD63, P70-75
This gene encodes the beta subunit of the interleukin-2 receptor, which transduces mitogenic signals from IL-2 and mediates receptor-mediated endocytosis in T cell-mediated immune responses. Biallelic mutations cause autosomal recessive immunodeficiency 63 with lymphoproliferation and autoimmunity. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.496), reflecting its important role in immune system function.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
521 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 5 | 2 | 19 | 0 | 26 |
Likely Pathogenic | 7 | 0 | 1 | 0 | 8 |
VUS | 7 | 197 | 10 | 3 | 217 |
Likely Benign | 0 | 9 | 84 | 136 | 229 |
Benign | 0 | 5 | 14 | 3 | 22 |
Conflicting | — | 8 | |||
| Total | 19 | 213 | 128 | 142 | 510 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IL2RB · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools