IL21
Chr 4ARinterleukin 21
Also known as: CVID11, IL-21, Za11
This gene encodes interleukin-21, a cytokine that regulates both innate and adaptive immune responses by inducing differentiation, proliferation and activity of B cells, T cells, natural killer cells, and macrophages, and is critical for antibody production and T follicular helper cell formation. Mutations cause autosomal recessive common variable immunodeficiency-11, affecting the immune system's ability to produce effective antibody responses. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.643), suggesting some tolerance for reduced function.
Primary Disease Associations & Inheritance
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
152 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 21 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 3 | 66 | 6 | 1 | 76 |
Likely Benign | 0 | 1 | 30 | 13 | 44 |
Benign | 0 | 0 | 6 | 2 | 8 |
Conflicting | — | 1 | |||
| Total | 3 | 68 | 64 | 16 | 152 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IL21 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells
RECRUITINGLentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
RECRUITINGRecombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Pancreatic Cancer
RECRUITINGDisease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches
NOT YET RECRUITINGCytokine Armored GPC3 Specific Chimeric Antigen Receptor Expressing T-cells in Adults With Solid Tumors
NOT YET RECRUITINGMethotrexate in Erosive Inflammatory Hand Osteoarthritis
ACTIVE NOT RECRUITINGThe Role of Cytokines and Regulatory T Lymphocytes in Migraine Pathophysiology.
RECRUITINGSafety of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Tumors
ACTIVE NOT RECRUITINGInterleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
RECRUITINGA-TANGO Phase 2 Study
NOT YET RECRUITINGA Study to Evaluate Combination Therapy of Oncolytic Vaccinia Virus (hV01) and PD-1 Inhibitor in Advanced Solid Tumors.
RECRUITINGMAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer
RECRUITINGExternal Resources
Links to major genomics databases and tools