IL16

Chr 15

interleukin 16

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

NCBI Gene: 3603 ENSG00000172349 UniProt: Q14005

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.

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

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?

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

Background carrier burden — how many people carry a rare variant somewhere in IL16?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 33

1,744 rare PASS variants

Rare truncating (LoF)

1 in 880

191 rare PASS variants

Rare synonymous (reference)

1 in 59

774 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL16. 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 46	1 in 1,100
South Asian	~43k	1 in 26	1 in 440
Remaining (unassigned)	~30k	1 in 28	1 in 940
European (Finnish)	~27k	1 in 120	1 in 1,300
Admixed American	~22k	1 in 28	1 in 900
African / African American	~21k	1 in 28	1 in 590
East Asian	~20k	1 in 38	1 in 510
Ashkenazi Jewish	~13k	1 in 110	1 in 970
Middle Eastern	~2,884	1 in 32	≈ 1 in 960

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): 17 of 18 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 18.? see exons ↓