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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IL16
interleukin 16
Chromosome 15 · 15q25.1
NCBI Gene: 3603Ensembl: ENSG00000172349.19HGNC: HGNC:5980UniProt: A0A8C8KBU6
206PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of interleukin-6 productionprotein bindingpositive regulation of interleukin-12 productionpositive regulation of inflammatory responsehair colorplacenta praeviaprimary biliary cirrhosisfacial morphology
✦AI Summary

Interleukin-16 (IL-16) is a pro-inflammatory cytokine that functions primarily as a CD4+ T cell chemoattractant and immunomodulatory molecule 1. IL-16 is synthesized as a precursor and processed by cleavage of a C-terminal 14 kDa peptide, which aggregates into bioactive tetramers that interact directly with CD4 receptors 2. Through CD4 binding, IL-16 induces chemotaxis of various CD4+ immune cells, promotes interleukin-2 receptor and HLA-DR expression, and can reversibly inhibit T cell receptor/CD3-dependent activation 2. The cytokine plays significant roles in inflammatory diseases, with elevated levels correlating with CD4+ T cell infiltration in asthma and serving as a biomarker in lupus nephritis, where it is highly expressed by infiltrating immune cells at sites of kidney injury 3. Recent studies demonstrate that IL-16 can be released through GSDME-mediated pyroptosis, particularly in inflammatory conditions like endometriosis 4. Genetic polymorphisms in IL16 have been associated with various diseases including alopecia areata, osteosarcoma susceptibility, and asparaginase-related thrombosis in leukemia patients 567. These findings highlight IL-16's potential as both a therapeutic target and biomarker for inflammatory and autoimmune conditions.

Sources cited
1
IL-16 functions as a CD4+ T cell chemoattractant and immunomodulatory cytokine
PMID: 10857846
2
IL-16 structure, processing mechanism, and CD4-dependent functions
PMID: 9451819
3
IL-16 role in lupus nephritis as biomarker and high expression by infiltrating immune cells
PMID: 34783463
4
IL-16 release through GSDME-mediated pyroptosis in endometriosis
PMID: 38508138
5
IL16 polymorphisms associated with alopecia areata susceptibility
PMID: 24320753
6
IL16 polymorphisms linked to osteosarcoma risk
PMID: 27703190
7
IL16 variants associated with asparaginase-related thrombosis
PMID: 36946317
Disease Associationsⓘ20
hair colorOpen Targets
0.39Weak
placenta praeviaOpen Targets
0.37Weak
primary biliary cirrhosisOpen Targets
0.28Weak
facial morphologyOpen Targets
0.22Weak
peritonitisOpen Targets
0.22Weak
neoplasmOpen Targets
0.11Weak
sarcopeniaOpen Targets
0.10Weak
infectionOpen Targets
0.09Suggestive
coronary artery diseaseOpen Targets
0.09Suggestive
systemic lupus erythematosusOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
myeloid sarcomaOpen Targets
0.09Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.08Suggestive
endometriosisOpen Targets
0.08Suggestive
Miyoshi myopathyOpen Targets
0.08Suggestive
type 1 diabetes mellitusOpen Targets
0.08Suggestive
Wilson diseaseOpen Targets
0.08Suggestive
autoimmune thrombocytopenic purpuraOpen Targets
0.08Suggestive
Townes-Brocks syndromeOpen Targets
0.07Suggestive
obesityOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCR5Protein interaction100%CD4Protein interaction100%IL1AProtein interaction100%IL17AProtein interaction97%TNFProtein interaction97%IL1BProtein interaction96%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
91%
Heart
19%
Ovary
18%
Liver
15%
Brain
3%
Gene Interaction Network
Click a node to explore
IL16CCR5CD4IL1AIL17ATNFIL1B
PROTEIN STRUCTURE
Preparing viewer…
PDB5FB8 · 2.07 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.78LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.62 [0.50–0.78]
RankingsWhere IL16 stands among ~20K protein-coding genes
  • #2,029of 20,598
    Most Researched206 · top 10%
  • #6,302of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedIL16
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Interleukin-16.
PMID: 10857846
J Leukoc Biol · 2000
1.00
2
Urine Proteomics and Renal Single-Cell Transcriptomics Implicate Interleukin-16 in Lupus Nephritis.
PMID: 34783463
Arthritis Rheumatol · 2022
0.90
3
Interleukin-16.
PMID: 9451819
Int J Biochem Cell Biol · 1997
0.80
4
PMID: 36946317
Pharmacogenomics · 2023
0.70
5
Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development.
PMID: 38508138
Cell Rep Med · 2024
0.60