IL16

Chr 15

interleukin 16

Also known as: LCF, NIL16, PRIL16, prIL-16

NCBI Gene: 3603 ENSG00000172349 UniProt: Q14005 OMIM: 603035

The protein functions as a pleiotropic cytokine that acts as a chemoattractant for CD4+ lymphocytes, monocytes, and eosinophils, and modulates T cell activation by priming CD4+ T-cells for cytokine responsiveness. Mutations in this gene cause autosomal dominant cold-induced autoinflammatory syndrome, characterized by recurrent episodes of fever, rash, and arthralgia triggered by cold exposure. The gene shows minimal constraint against loss-of-function variants, suggesting tolerance to such mutations in the general population.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.69

Clinical Summary— IL16

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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

199 VUS of 243 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.000

Z-score 3.35

OE 0.49 (0.36–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.70Z-score

OE missense 0.93 (0.87–0.99)

697 obs / 751.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.36–0.69)

0≤0.351.4

Missense OE?0.93 (0.87–0.99)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 25 / 50.8Missense obs/exp: 697 / 751.0Syn Z: -0.84

This gene — mechanism propensity

0.6648th %ile

GOF

0.6247th %ile

LOF

0.4627th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

243 submitted variants in ClinVar

ClinVar

Classification Summary

VUS199

Likely Benign18

Benign7

199

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	199	0	0	199
Likely Benign	13	1	4	18
Benign	3	1	3	7
Total	215	2	7	224

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

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22 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap IL16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →