IL2RA

Chr 10AR

interleukin 2 receptor subunit alpha

Also known as: CD25, IDDM10, IL2R, IMD41, TCGFR, p55

The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-affinity IL2 receptor. Homodimeric alpha chains (IL2RA) result in low-affinity receptor, while homodimeric beta (IL2RB) chains produce a medium-affinity receptor. Normally an integral-membrane protein, soluble IL2RA has been isolated and determined to result from extracellular proteolyisis. Alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is presently unknown. Mutations in this gene are associated with interleukin 2 receptor alpha deficiency. Patients with severe Coronavirus Disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have significantly elevated levels of IL2R in their plasma. Similarly, serum IL-2R levels are found to be elevated in patients with different types of carcinomas. Certain IL2RA and IL2RB gene polymorphisms have been associated with lung cancer risk. [provided by RefSeq, Jul 2020]

Primary Disease Associations & Inheritance

{Diabetes, mellitus, insulin-dependent, susceptibility to, 10}MIM #601942
Immunodeficiency 41 with lymphoproliferation and autoimmunityMIM #606367
AR
UniProtType 1 diabetes mellitus 10
5
Active trials
61
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.66
LOEUF
Multiple*
Mechanism· predicted
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
5 active or recruiting trials — potential therapeutic options may be available

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.

Clinical Literature
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