IL27

Chr 16

interleukin 27

Also known as: IL-27, IL-27A, IL27A, IL27p28, IL30, p28

NCBI Gene: 246778 ENSG00000197272 UniProt: Q8NEV9 OMIM: 608273

The IL27 protein associates with EBI3 to form the IL-27 cytokine complex, which regulates T-helper cell development, suppresses T-cell proliferation, stimulates cytotoxic T-cell activity, and has diverse effects on innate immune cells including driving clonal expansion of naive CD4+ T-cells and synergizing with IL-12 to trigger interferon-gamma production. Mutations in IL27 cause immunodeficiency with autosomal recessive inheritance, affecting immune system function. This gene shows high constraint against loss-of-function variants, indicating it is essential for normal cellular function.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is one of the subunits of a heterodimeric cytokine complex. This protein is related to interleukin 12A (IL12A). It interacts with Epstein-Barr virus induced gene 3 (EBI3), a protein similar to interleukin 12B (IL12B), and forms a complex that has been shown to drive rapid expansion of naive but not memory CD4(+) T cells. The complex is also found to synergize strongly with interleukin 12 to trigger interferon gamma (IFNG) production of naive CD4(+) T cells. The biological effects of this cytokine are mediated by the class I cytokine receptor (WSX1/TCRR). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.51

Clinical Summary— IL27

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.

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ClinVar Variants

31 VUS of 41 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.782

Z-score 2.54

OE 0.11 (0.04–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.08Z-score

OE missense 0.75 (0.64–0.88)

112 obs / 149.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.51)

0≤0.351.4

Missense OE?0.75 (0.64–0.88)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 1 / 9.4Missense obs/exp: 112 / 149.3Syn Z: 1.32

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS31

Likely Benign5

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	30	1	0	31
Likely Benign	4	0	1	5
Benign	1	0	0	1
Total	35	1	1	37

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

View in ClinVar →

68 pathogenic / likely-pathogenic (of 90) ClinVar copy-number / structural variants overlap IL27 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →