IL18BP

Chr 11AR

interleukin 18 binding protein

Also known as: FVH, IL18BPa

NCBI Gene: 10068ENSG00000137496UniProt: O95998

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]

Primary Disease Associations & Inheritance

{?Hepatitis, fulminant viral, susceptibility to}MIM #618549
AR
305
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— IL18BP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 217 VUS of 305 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.55Z-score
OE missense 1.15 (0.99–1.33)
126 obs / 109.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.19 (0.74–1.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (0.99–1.33)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 11 / 9.2Missense obs/exp: 126 / 109.7Syn Z: -0.75

ClinVar Variant Classifications

305 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS217
Likely Benign66
Benign10
Conflicting4
8
Pathogenic
217
VUS
66
Likely Benign
10
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
12
167
26
12
217
Likely Benign
0
16
20
30
66
Benign
0
4
4
2
10
Conflicting
—4
Total121875844305

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

View in ClinVar →

Protein Context — Lollipop Plot

IL18BP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{?Hepatitis, fulminant viral, susceptibility to}

MIM #618549

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mechanisms of Hepatocellular Injury in Hepatitis A.
Wang M et al.·Viruses
2021Review
IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy.
Zhou T et al.·Nature
2020
Hyperferritinemia Screening to Aid Identification and Differentiation of Patients with Hyperinflammatory Disorders.
Carol HA et al.·J Clin Immunol
2024Cohort
SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy.
Liang S et al.·Signal Transduct Target Ther
2023
Suppression of multiple mouse models of refractory malignancies by reprogramming IL-18 ligand-receptor interaction.
Fan Z et al.·Nat Commun
2025Functional
NETs activate the GAS6-AXL-NLRP3 axis in macrophages to drive morphine tolerance.
Tian Q et al.·Cell Commun Signal
2025
Combined delivery of IL12 and an IL18 mutant without IL18BP-binding activity by an adenoviral vector enhances tumor specific immunity.
Cheng Y et al.·Sci Rep
2025
IL-18 and IL-18BP: A Unique Dyad in Health and Disease.
Novick D·Int J Mol Sci
2024Review
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma.
Schoenfeld DA et al.·JCI Insight
2024
Interleukin-18 binding protein protects against metabolic steatohepatitis.
Somm E et al.·Hepatol Commun
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools