IL2

Chr 4

interleukin 2

Also known as: IL-2, TCGF, lymphokine

NCBI Gene: 3558 ENSG00000109471 UniProt: P60568 OMIM: 147680

This gene encodes interleukin-2, a cytokine secreted by activated T cells that promotes T and B cell proliferation, regulates immune tolerance through regulatory T cells, and activates natural killer cells via JAK-STAT signaling pathways. Mutations cause severe combined immunodeficiency with autoimmunity, alopecia, and erythroderma (SCIDAAE), an autosomal recessive primary immunodeficiency presenting in infancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.81), reflecting its critical role in immune system regulation.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli. [provided by RefSeq, Sep 2020]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

282

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

GOF

Mechanism· predicted

📖

GeneReview available — IL2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.480

Z-score 1.86

OE 0.17 (0.06–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.43Z-score

OE missense 0.53 (0.41–0.69)

38 obs / 72.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.06–0.81)

0≤0.351.4

Missense OE?0.53 (0.41–0.69)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 1 / 5.9Missense obs/exp: 38 / 72.2Syn Z: -1.14

Background carrier burden — how many people carry a rare variant somewhere in IL2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,100

134 rare PASS variants

Rare truncating (LoF)

1 in 45,000

12 rare PASS variants

Rare synonymous (reference)

1 in 2,100

73 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~555k	1 in 1,900	1 in 55,000
South Asian	~43k	1 in 580	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 1,100	none seen
European (Finnish)	~27k	≈ 1 in 6,600	≈ 1 in 27,000
Admixed American	~22k	1 in 500	none seen
African / African American	~21k	1 in 1,100	none seen
East Asian	~20k	1 in 600	≈ 1 in 6,600
Middle Eastern	~2,881	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 4.? see exons ↓