IL2RB

Chr 22AR

interleukin 2 receptor subunit beta

Also known as: CD122, IL15RB, IMD63, P70-75

NCBI Gene: 3560 ENSG00000100385 UniProt: P14784 OMIM: 146710

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. The low affinity form is a monomer of the alpha subunit and is not involved in signal transduction. The intermediate affinity form consists of an alpha/beta subunit heterodimer, while the high affinity form consists of an alpha/beta/gamma subunit heterotrimer. Both the intermediate and high affinity forms of the receptor are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. The protein encoded by this gene represents the beta subunit and is a type I membrane protein. The use of alternative promoters results in multiple transcript variants encoding the same protein. The protein is primarily expressed in the hematopoietic system. The use by some variants of an alternate promoter in an upstream long terminal repeat (LTR) results in placenta-specific expression. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.501 OMIM phenotype

Clinical Summary— IL2RB

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Gene-Disease Validity (ClinGen)

immunodeficiency 63 with lymphoproliferation and autoimmunity · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.291

Z-score 3.26

OE 0.24 (0.12–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.44Z-score

OE missense 0.93 (0.84–1.02)

284 obs / 305.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.12–0.50)

0≤0.351.4

Missense OE?0.93 (0.84–1.02)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 5 / 21.2Missense obs/exp: 284 / 305.7Syn Z: 0.18

This gene — mechanism propensity

0.7035th %ile

GOF

0.78top 25%

LOF

0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). 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.

GOFprediction above median

DNprediction above median

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.