IL32

Chr 16

interleukin 32

Also known as: IL-32alpha, IL-32beta, IL-32delta, IL-32gamma, NK4, TAIF, TAIFa, TAIFb

This gene encodes a cytokine that induces production of TNF-alpha from macrophages and activates NF-kappa-B and p38 MAPK signaling pathways in immune responses. Mutations cause autosomal dominant autoinflammatory disease with immunodeficiency. The gene is highly intolerant to loss-of-function mutations, suggesting complete loss of protein function may be incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.92
Clinical SummaryIL32
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.92LOEUF
pLI 0.000
Z-score -1.11
OE 1.43 (0.881.92)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.35Z-score
OE missense 1.66 (1.471.88)
165 obs / 99.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.43 (0.881.92)
00.351.4
Missense OE1.66 (1.471.88)
00.61.4
Synonymous OE1.56
01.21.6
LoF obs/exp: 11 / 7.7Missense obs/exp: 165 / 99.2Syn Z: -2.70
DN
0.6839th %ile
GOF
0.77top 25%
LOF
0.2385th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IL32 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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