IL2RA

Chr 10AR

interleukin 2 receptor subunit alpha

The interleukin-2 receptor alpha chain controls immune tolerance by regulating regulatory T cell activity, which suppresses autoreactive T cell activation and expansion. Autosomal recessive mutations cause immunodeficiency with lymphoproliferation and autoimmunity, and confer susceptibility to insulin-dependent diabetes mellitus. This gene is moderately constrained against loss-of-function variation (LOEUF 0.658).

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.662 OMIM phenotypes
Clinical SummaryIL2RA
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Gene-Disease Validity (ClinGen)
immunodeficiency due to CD25 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.055
Z-score 2.55
OE 0.31 (0.160.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.36Z-score
OE missense 0.92 (0.801.05)
145 obs / 157.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.160.66)
00.351.4
Missense OE0.92 (0.801.05)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 5 / 16.0Missense obs/exp: 145 / 157.8Syn Z: -0.84
DN
0.6646th %ile
GOF
0.6735th %ile
LOF
0.1796th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IL2RA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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