IL2

Chr 4

interleukin 2

Also known as: IL-2, TCGF, lymphokine

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.

Summary from RefSeq, UniProt
Research Assistant →
12
Active trials
175
Pubs (1 yr)
23
P/LP submissions
0%
P/LP missense
0.81
LOEUF
GOF
Mechanism· predicted
Clinical SummaryIL2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.17) despite low pLI — interpret in context.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 3 VUS of 27 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — IL2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.480
Z-score 1.86
OE 0.17 (0.060.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.43Z-score
OE missense 0.53 (0.410.69)
38 obs / 72.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.060.81)
00.351.4
Missense OE0.53 (0.410.69)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 1 / 5.9Missense obs/exp: 38 / 72.2Syn Z: -1.14
DN
0.5771th %ile
GOF
0.6444th %ile
LOF
0.3165th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

27 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS3
Likely Benign1
22
Pathogenic
1
Likely Pathogenic
3
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
21
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
0
3
0
3
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total1125027

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IL2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Solid Tumors

TCR-T Cells for the Treatment NY-ESO-1-positive Advanced Solid Tumors

NOT YET RECRUITING
NCT05648994Phase EARLY_PHASE1Fujian Cancer HospitalStarted 2022-12
TCR-T cellsFludarabineCyclophosphamide Capsules
Parkinson DiseasePhysical InactivityPhysical Disability

Physical Activity on Neuroinflammation in Parkinson's Disease

RECRUITING
NCT06977204IRCCS National Neurological Institute "C. Mondino" FoundationStarted 2023-01-01
EndometriosisAdenomyosis

Pain in Endometriosis And the Relation to Lifestyle

RECRUITING
NCT06332560Phase NARadboud University Medical CenterStarted 2024-10-04
Anti-inflammatory diet (DI)Cognitive behavioral therapy (CBT)
Melanoma

Adoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes

RECRUITING
NCT02870244Phase PHASE1Loyola UniversityStarted 2015-02
Escalating Doses
EBV Infection After Allogenic HSCT

Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT

RECRUITING
NCT06119256Phase PHASE1Chinese PLA General HospitalStarted 2023-08-01
EBV-TCR-T cells
Metastatic Castration-resistant Prostate Cancer (mCRPC)

Phase 1 Study Evaluating Safety and Tolerability of SL-T10, GX-I7, and Pembrolizumab Triple Combination in mCRPC.

RECRUITING
NCT06344715Phase PHASE1SL VAXiGENStarted 2022-10-17
SL-T10GX-I7Pembrolizumab
DysferlinopathyMiyoshi MyopathyLGMDR2

Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF

ENROLLING BY INVITATION
NCT04824040Artgen BiotechStarted 2020-01-15
Rare Malignant NeoplasmAdvanced Solid TumorsMetastatic Solid Tumors

Rare Tumor Focused Platform Study of Innovative Therapies and Technologies (PLATFORM2)

NOT YET RECRUITING
NCT07307053Phase PHASE1, PHASE2Cancer Institute and Hospital, Chinese Academy of Medical SciencesStarted 2026-01-01
BL-B01D1VSV injectionCVL006
Obsessive-Compulsive Disorder

Reinforcement Learning and Obsessive-compulsive Disorder: Exploring the Role of the Orbitofrontal Cortex

RECRUITING
NCT06566781Fundacao ChampalimaudStarted 2019-10-01
Aging

Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging

ACTIVE NOT RECRUITING
NCT07114536Phase NAShenzhen Hygieia Biotech Co., LtdStarted 2025-08-20
Calcium-a-ketoglutaratePlacebo(starch)
Systemic Histiocytosis (Disorder)

Biomarkers in Systemic Histiocytosis

NOT YET RECRUITING
NCT07157683Assistance Publique - Hôpitaux de ParisStarted 2025-10-01
Biospecimen collection
Autoimmune Lymphoproliferative Syndrome

Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

RECRUITING
NCT06730126Phase PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2025-03-10
Soquelitinib
Clinical Literature
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