IL4R

Chr 16

interleukin 4 receptor

Also known as: CD124, IL-4RA, IL4RA

NCBI Gene: 3566ENSG00000077238UniProt: P24394

This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE production. The encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

179
ClinVar variants
32
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— IL4R
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 105 VUS of 179 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
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.
0.83LOEUF
pLI 0.000
Z-score 2.11
OE 0.48 (0.29–0.83)
Tolerant

Typical tolerance to LoF variation

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.
0.77Z-score
OE missense 0.90 (0.83–0.98)
428 obs / 475.2 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.0.48 (0.29–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.83–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 9 / 18.9Missense obs/exp: 428 / 475.2Syn Z: 0.24

ClinVar Variant Classifications

179 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic3
VUS105
Likely Benign24
Benign17
Conflicting1
29
Pathogenic
3
Likely Pathogenic
105
VUS
24
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
3
0
3
VUS
0
95
10
0
105
Likely Benign
0
18
2
4
24
Benign
0
8
2
7
17
Conflicting
—1
Total01214611179

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

View in ClinVar →

Protein Context — Lollipop Plot

IL4R · 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

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mechanisms of Dupilumab.
Harb H et al.·Clin Exp Allergy
2020Review
Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs.
Müller S et al.·Allergy
2024Review
Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.
Alig SK et al.·Nature
2024
Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells.
Bangert C et al.·Nat Commun
2024
Biologics in congenital ichthyosis: are they effective?
Mazereeuw-Hautier J et al.·Br J Dermatol
2025
IL4 receptor targeting enables nab-paclitaxel to enhance reprogramming of M2-type macrophages into M1-like phenotype via ROS-HMGB1-TLR4 axis and inhibition of tumor growth and metastasis.
Vadevoo SMP et al.·Theranostics
2024
CD23(+)IgG1(+) memory B cells are poised to switch to pathogenic IgE production in food allergy.
Ota M et al.·Sci Transl Med
2024
Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years.
Guttman-Yassky E et al.·Allergy
2024Clinical trial
IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases.
Aranda CJ et al.·Allergy
2023
Targeting IL4/IL4R for the treatment of epithelial cancer metastasis.
Bankaitis KV et al.·Clin Exp Metastasis
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Asthma, Allergic

Dupilumab Effects Against Aeroallergen Challenge

RECRUITING
NCT05720325Phase PHASE2The University of Texas Health Science Center at San AntonioStarted 2023-03-29
DupilumabHouse Dust Mites (HDM)Placebo
Asthma

Investigating Dupilumab's Effect in Asthma by Genotype

ACTIVE NOT RECRUITING
NCT03694158Phase PHASE4Boston Children's HospitalStarted 2021-09-08
DupilumabPlacebo
Moderate to Severe Asthma

Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and Endotyping

RECRUITING
NCT06385236Phase PHASE4University of California, San DiegoStarted 2024-02-19
DupilumabBenralizumab
Asthma

Genetic Association With Various Severities, Phenotypes and Endotypes of Asthma.

RECRUITING
NCT06196034Chinese University of Hong KongStarted 2024-03-01
No intervention

External Resources

Links to major genomics databases and tools