IL4

Chr 5

interleukin 4

Also known as: BCGF-1, BCGF1, BSF-1, BSF1, IL-4

The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. IL4 is considered an important cytokine for tissue repair, counterbalancing the effects of proinflammatory type 1 cytokines, however, it also promotes allergic airway inflammation. Moreover, IL-4, a type 2 cytokine, mediates and regulates a variety of human host responses such as allergic, anti-parasitic, wound healing, and acute inflammation. This cytokine has been reported to promote resolution of neutrophil-mediated acute lung injury. In an allergic response, IL-4 has an essential role in the production of allergen-specific immunoglobin (Ig) E. This pro-inflammatory cytokine has been observed to be increased in COVID-19 (Coronavirus disease 2019) patients, but is not necessarily associated with severe COVID-19 pathology. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

UniProtIschemic stroke
35
ClinVar variants
14
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical SummaryIL4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 19 VUS of 35 total submissions
💊
Clinical Trials
12 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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.52LOEUF
pLI 0.005
Z-score 0.70
OE 0.69 (0.341.52)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.35Z-score
OE missense 0.90 (0.751.08)
80 obs / 89.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.341.52)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.751.08)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
01.21.6
LoF obs/exp: 4 / 5.8Missense obs/exp: 80 / 89.2Syn Z: -0.43

ClinVar Variant Classifications

35 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS19
Likely Benign1
Benign1
13
Pathogenic
1
Likely Pathogenic
19
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
17
2
0
19
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total01717135

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

View in ClinVar →

Protein Context — Lollipop Plot

IL4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

INTERLEUKIN 4; IL4
MIM #147780 · *
Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

HivHBV Coinfection

Towards a Functional Cure for HBV - The COMMIT Cohort Study

ACTIVE NOT RECRUITING
NCT03645044University of MelbourneStarted 2018-05-24
High-grade GliomaWHO Grade Ⅳ Glioma

Safety and Efficacy Study of TX103 CAR-T Cell Therapy for Recurrent or Progressive Grade 4 Glioma.

RECRUITING
NCT06482905Phase PHASE1Tcelltech Inc.Started 2024-09-04
Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
Hyperparathyroidism, Primary

Primary Hyperparathyroidism and Gut Microbiota

RECRUITING
NCT04948671Centre Hospitalier Universitaire VaudoisStarted 2021-11-17
there will be no intervention, this is an observational study
Hand OsteoarthritisErosive Osteoarthritis

Methotrexate in Erosive Inflammatory Hand Osteoarthritis

ACTIVE NOT RECRUITING
NCT04579848Phase PHASE4Diakonhjemmet HospitalStarted 2021-08-12
Methotrexate TabletsPlaceboFolic Acid 1 MG
Coronary Heart Disease

Adipose Tissue and Inflammation in Coronary Heart Disease

ACTIVE NOT RECRUITING
NCT02760914Oslo University HospitalStarted 2016-06
Cerebral Blood FlowAPOE 4

A Nutritional Intervention for Body, Brain, and Longevity Effects (NIBBLE)

NOT YET RECRUITING
NCT06682767Phase NACedars-Sinai Medical CenterStarted 2026-03
FMD1 (LNT22-017-1)Dietary Guidance
Menopause

Menopausal Symptoms Probiotic Study

RECRUITING
NCT06446869Phase NACommunity Pharmacology Services LtdStarted 2024-09-10
Gyntima MenopausePlacebo
Mild Cognitive ImpairmentAlzheimer Disease

Effects of Yeast Beta-glucan on Cognitive Function in Patients With Mild Cognitive Impairment

ACTIVE NOT RECRUITING
NCT06083350Phase NAXiaofan XuStarted 2023-06-27
Yeast beta-glucanStarch
Crohn's Disease

Impact of Diet and Lifestyle Modification on the Intestinal Barrier Integrity in Crohn's Disease

RECRUITING
NCT06719778Phase NAUniversität Duisburg-EssenStarted 2024-08-01
Two-stage nutritional therapy concept
Ulcerative Colitis (UC)Crohn Disease (CD)

Wild Blueberries in Colitis

RECRUITING
NCT06698601Phase NAUniversität Duisburg-EssenStarted 2024-09-24
blueberry-rich dietControl diet
Gastric Cancer

Phase I Trial of CEA Specific AAV-DC-CTL Treatment in Stage IV Gastric Cancer

ACTIVE NOT RECRUITING
NCT02496273Phase PHASE1The First People's Hospital of ChangzhouStarted 2016-01
CTL
Healthy AdultsHigh AltitudeIsolation, Social

Human Milk Oligosaccharides (HMOs) and Gut Microbiota, Immune System in Antarctica

ENROLLING BY INVITATION
NCT06133530Phase NAIU University of Applied SciencesStarted 2023-09-24
Human milk oligosaccharidesMaltose