IL4R

Chr 16

interleukin 4 receptor

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

NCBI Gene: 3566ENSG00000077238UniProt: P24394OMIM: 147781

The IL4R protein is the alpha chain of the interleukin-4 receptor that binds IL-4 and IL-13 to regulate IgE production and promote Th2 cell differentiation through the JAK-STAT6 pathway. Mutations are associated with atopy manifesting as allergic rhinitis, asthma, eczema, or sinusitis, with autosomal recessive inheritance patterns reported for severe forms. The gene shows low constraint to loss-of-function variation, suggesting tolerance to reduced protein levels.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.83
Clinical Summary— IL4R
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 66 VUS of 102 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.11
OE 0.48 (0.29–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.77Z-score
OE missense 0.90 (0.83–0.98)
428 obs / 475.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.29–0.83)
0≤0.351.4
Missense OE0.90 (0.83–0.98)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 9 / 18.9Missense obs/exp: 428 / 475.2Syn Z: 0.24
DN
0.7228th %ile
GOF
0.78top 25%
LOF
0.3066th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation
DNprediction 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.

Literature Evidence

GOFHere, we describe novel somatic IL4R mutations in 15 of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8, leading to an I242N amino acid change in the transmembrane domain. FunctionaPMID:29467182

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS66
Likely Benign13
Benign1
2
Pathogenic
1
Likely Pathogenic
66
VUS
13
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
1
0
1
VUS
0
65
1
0
66
Likely Benign
0
13
0
0
13
Benign
0
1
0
0
1
Total0794083

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Modulating tumor-associated macrophages through APP-CD74 blockade with IL4R-exosomes synergizes with PD-1 inhibition in gastric cancer.
Chen O et al.·NPJ Precis Oncol
2026
Recognition of pivotal immune genes NR1H4 and IL4R as diagnostic biomarkers in distinguishing ovarian clear cell cancer from high-grade serous cancer.
Ke Y et al.·Front Mol Biosci
2025Open Access
Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.
Chen HH et al.·Cell Genom
2025Open Access
Long non-coding RNA LBX2-AS1 activates IL4R to promote glioblastoma metastasis and angiogenesis by binding to the transcription factor NFKB1.
Li Q et al.·Folia Neuropathol
2024
Anti-cancer activity of microbubble conjugated with Sorafenib containing liposome and IL4R-targeting peptide in kidney cancer cells.
Lee J et al.·Cell Mol Biol (Noisy-le-grand)
2023
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients