IL4

Chr 5

interleukin 4

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

NCBI Gene: 3565 ENSG00000113520 UniProt: P05112 OMIM: 147780

IL4 encodes interleukin-4, a cytokine that regulates antibody production (particularly IgE and IgG1), hematopoiesis, inflammation, and T-cell responses through STAT6 signaling, and also plays a role in memory and learning functions. The gene shows low constraint to loss-of-function variation (pLI = 0.005, LOEUF = 1.52), and while IL4 variants have been associated with immunological phenotypes, well-established Mendelian neurological disorders caused by IL4 mutations are not currently recognized in major clinical databases.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIschemic stroke

Active trials

318

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.52

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.005

Z-score 0.70

OE 0.69 (0.34–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.90 (0.75–1.08)

80 obs / 89.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.34–1.52)

0≤0.351.4

Missense OE?0.90 (0.75–1.08)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 4 / 5.8Missense obs/exp: 80 / 89.2Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in IL4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

220 rare PASS variants

Rare truncating (LoF)

1 in 4,500

28 rare PASS variants

Rare synonymous (reference)

1 in 650

77 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 6,500
South Asian	~43k	1 in 200	1 in 8,600
Remaining (unassigned)	~30k	1 in 210	1 in 3,400
European (Finnish)	~27k	1 in 1,400	1 in 1,500
Admixed American	~22k	1 in 180	1 in 3,700
African / African American	~21k	1 in 120	1 in 2,000
East Asian	~20k	1 in 190	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 930	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 960	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 4.? see exons ↓