IL18

Chr 11

interleukin 18

Also known as: IGIF, IL-18, IL-1g, IL1F4

NCBI Gene: 3606 ENSG00000150782 UniProt: Q14116

The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]

Research

ResearchGenerating clinical summary…

Active trials

230

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.28

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.28LOEUF

pLI 0.031

Z-score 1.13

OE 0.50 (0.23–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.52Z-score

OE missense 0.55 (0.44–0.70)

51 obs / 92.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.23–1.28)

0≤0.351.4

Missense OE?0.55 (0.44–0.70)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 3 / 6.0Missense obs/exp: 51 / 92.0Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in IL18?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 570

178 rare PASS variants

Rare truncating (LoF)

1 in 14,000

23 rare PASS variants

Rare synonymous (reference)

1 in 2,300

70 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL18. 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 630	1 in 17,000
South Asian	~43k	1 in 490	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 630	1 in 1,000
European (Finnish)	~27k	1 in 5,200	≈ 1 in 13,000
Admixed American	~22k	1 in 630	1 in 4,000
African / African American	~21k	1 in 600	≈ 1 in 16,000
East Asian	~20k	1 in 210	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 12,000	none seen
Middle Eastern	~2,884	1 in 570	≈ 1 in 2,700

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): 2 of 5 coding exons well covered in gnomAD exomes; exons 3, 4, 5 marginal. Genomes: all 5.? see exons ↓