IL21

Chr 4

interleukin 21

Also known as: CVID11, IL-21, Za11

This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtImmunodeficiency, common variable, 11

Clinical highlights

Gene-disease validity (ClinGen)
IL21-related infantile inflammatory bowel disease · ARLimitednot for standalone diagnostic reporting
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.
12
Active trials
44
Pubs (1 yr)
P/LP submissions
P/LP missense
0.64
LOEUF
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.64LOEUF
pLI 0.625
Z-score 2.18
OE 0.14 (0.050.64)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?
1.54Z-score
OE missense 0.53 (0.410.68)
44 obs / 83.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.14 (0.050.64)
00.351.4
Missense OE?0.53 (0.410.68)
00.61.4
Synonymous OE?0.39
01.21.6
LoF obs/exp: 1 / 7.4Missense obs/exp: 44 / 83.6Syn Z: 2.56

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Advanced Solid Tumors

Safety of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Tumors

ACTIVE NOT RECRUITING
NCT05914376Phase PHASE1Hangzhou Converd Co., Ltd.Started 2023-07-05
Recombinant human IL-21-expressing oncolytic vaccinia virus injection
Liver CancerRhabdomyosarcomaMalignant Rhabdoid Tumor

Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

RECRUITING
NCT04715191Phase PHASE1Baylor College of MedicineStarted 2024-05-24
CARE T cells
Solid Tumor (Excluding CNS)Hepatocellular CarcinomaLiver Cell Carcinoma

Cytokine Armored GPC3 Specific Chimeric Antigen Receptor Expressing T-cells in Adults With Solid Tumors

NOT YET RECRUITING
NCT07224568Phase PHASE1Seattle Children's HospitalStarted 2026-04-01
SC-CAR.GPC3xIL15.21 CAR T cells
Acute-On-Chronic Liver FailureAlcoholic HepatitisLiver Cirrhosis, Alcoholic

A-TANGO Phase 2 Study

NOT YET RECRUITING
NCT06890039Phase PHASE2Yaqrit LtdStarted 2025-09-01
PlaceboTAK-242G-CSF (Filgrastim)
MelanomaMelanoma, UvealHead and Neck Cancer

MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer

RECRUITING
NCT04729543Phase PHASE1, PHASE2Erasmus Medical CenterStarted 2020-10-20
Adoptive therapy with autologous MC2 TCR T cells
ALS (Amyotrophic Lateral Sclerosis)FTDNeuropathic

Disease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches

ACTIVE NOT RECRUITING
NCT06856850Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaStarted 2025-02-27
X-linked Severe Combined Immunodeficiency (XSCID)

Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)

RECRUITING
NCT01306019Phase PHASE1, PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2012-09-25
Ex vivo culture and transduction of the patient's autologous CD34+ HSC with lentivirus vector VSV-G pseudotyped CL20- 4i-EF1alpha-hgammac-OPT vectorBusulfanPalifermin
Hand OsteoarthritisErosive Osteoarthritis

Methotrexate in Erosive Inflammatory Hand Osteoarthritis

ACTIVE NOT RECRUITING
NCT04579848Phase PHASE4Diakonhjemmet HospitalStarted 2021-08-12
Methotrexate TabletsPlaceboFolic Acid 1 MG
Migraine DisordersPainAutoimmune Diseases

The Role of Cytokines and Regulatory T Lymphocytes in Migraine Pathophysiology.

RECRUITING
NCT06426316Phase NAUniversity Hospital, Clermont-FerrandStarted 2025-06-02
Blood test
Advanced Solid Tumors

A Study to Evaluate Combination Therapy of Oncolytic Vaccinia Virus (hV01) and PD-1 Inhibitor in Advanced Solid Tumors.

RECRUITING
NCT07185243Phase NAHangzhou Converd Co., Ltd.Started 2025-06-23
recombinant human IL-21-expressing oncolytic vaccinia virus injection
Advanced Pancreatic Cancer

Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Pancreatic Cancer

RECRUITING
NCT07006077Phase PHASE2Hangzhou Converd Co., Ltd.Started 2025-05-29
Recombinant human IL-21-expressing oncolytic vaccinia virus injection
HepatoblastomaHepatocellular CarcinomaWilms Tumor

Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells

RECRUITING
NCT06198296Phase PHASE1Baylor College of MedicineStarted 2025-06-10
21.15.GPC3-CAR T cells