IL18BP

Chr 11

interleukin 18 binding protein

Also known as: FVH, IL18BPa

NCBI Gene: 10068 ENSG00000137496 UniProt: O95998

This gene encodes interleukin-18 binding protein, which inhibits the proinflammatory cytokine IL-18 by binding to it and preventing IL-18 from activating its receptor, thereby reducing interferon-gamma production and T-helper type 1 immune responses. Autosomal recessive mutations cause susceptibility to fulminant viral hepatitis. The gene shows minimal constraint against loss-of-function variants (pLI near zero, LOEUF 1.82), suggesting tolerance to reduced protein levels in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHepatitis, fulminant viral

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.82

LOEUF

GOF

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?

1.82LOEUF

pLI 0.000

Z-score -0.54

OE 1.19 (0.74–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.55Z-score

OE missense 1.15 (0.99–1.33)

126 obs / 109.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.19 (0.74–1.82)

0≤0.351.4

Missense OE?1.15 (0.99–1.33)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 11 / 9.2Missense obs/exp: 126 / 109.7Syn Z: -0.75

Background carrier burden — how many people carry a rare variant somewhere in IL18BP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

327 rare PASS variants

Rare truncating (LoF)

1 in 1,500

83 rare PASS variants

Rare synonymous (reference)

1 in 420

124 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL18BP. 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 190	1 in 1,700
South Asian	~43k	1 in 110	1 in 560
Remaining (unassigned)	~30k	1 in 95	1 in 1,500
European (Finnish)	~27k	1 in 2,000	1 in 1,800
Admixed American	~22k	1 in 110	≈ 1 in 5,500
African / African American	~21k	1 in 99	1 in 1,300
East Asian	~20k	1 in 99	1 in 990
Ashkenazi Jewish	~13k	1 in 450	none seen
Middle Eastern	~2,884	1 in 190	none seen

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓