IL32

Chr 16

interleukin 32

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

NCBI Gene: 9235 ENSG00000008517 UniProt: P24001 OMIM: 606001

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the cytokine family. The protein contains a tyrosine sulfation site, 3 potential N-myristoylation sites, multiple putative phosphorylation sites, and an RGD cell-attachment sequence. Expression of this protein is increased after the activation of T-cells by mitogens or the activation of NK cells by IL-2. This protein induces the production of TNFalpha from macrophage cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.92

Clinical Summary— IL32

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

55 VUS of 96 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.92LOEUF

pLI 0.000

Z-score -1.11

OE 1.43 (0.88–1.92)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.35Z-score

OE missense 1.66 (1.47–1.88)

165 obs / 99.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.43 (0.88–1.92)

0≤0.351.4

Missense OE?1.66 (1.47–1.88)

0≤0.61.4

Synonymous OE?1.56

0≤1.21.6

LoF obs/exp: 11 / 7.7Missense obs/exp: 165 / 99.2Syn Z: -2.70

This gene — mechanism propensity

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

96 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

Likely Benign6

Benign8

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	55	0	0	55
Likely Benign	1	2	2	1	6
Benign	0	5	1	2	8
Total	1	62	3	3	69

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap IL32 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →