IL16
protein-codinginterleukin 16, the group of PDZ domain containing|Interleukins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~154.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IL16 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_172217.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 3 | 8 | ||
| missense | 194 | 13 | 3 | 210 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 196 | 17 | 6 | 219 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_757366.2 | 18 | MANE Select | |
| Ensembl | ENSP00000508085.1 | 18 | MANE Select | |
| RefSeq | NP_001165599.1 | 18 | Standard | |
| RefSeq | NP_001339613.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Other interleukin signaling
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- JAK STAT MolecularVariation 1
- GPCR signaling-G alpha q
Biological Process
- immune response
- regulation of signaling receptor activity
- viral process
- cytokine-mediated signaling pathway
- leukocyte chemotaxis
Molecular Function
- cytokine activity
- CD4 receptor binding
Cellular Component
- extracellular region
- extracellular space
- cytosol
- plasma membrane
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302987
- Coding exons
- 18
- Length
- 153189
- Individuals with no LoFs
- 125636
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 111
- Defined
- 125748
- p
- 0.000445
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.700 | 697 | 751 | 0.928 | 0.0000422 | 8592 |
| Missense (PolyPhen) | 204 | 242.58 | 0.84097 | 2760 | ||
| Synonymous | -0.843 | 330 | 311 | 1.06 | 0.0000186 | 2826 |
| Loss of Function | 3.35 | 25 | 50.8 | 0.492 | 0.00000271 | 604 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00058 | 0.00055 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00041 | 0.00040 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.00036 | 0.00035 | rare |
| South Asian | 0.0011 | 0.0010 | notable |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4.; FUNCTION: Isoform 3 is involved in cell cycle progression in T- cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells.;
Recessive Scores
- pRec
- 0.192
Intolerance Scores
- LoFtool
- 0.717
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 47.8
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.948
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |