IL15
protein-codinginterleukin 15, the group of Interleukins
Gene summary
The protein encoded by this gene is a cytokine that regulates T and natural killer cell activation and proliferation. This cytokine and interleukine 2 share many biological activities. They are found to bind common hematopoietin receptor subunits, and may compete for the same receptor, and thus negatively regulate each other's activity. The number of CD8+ memory cells is shown to be controlled by a balance between this cytokine and IL2. This cytokine induces the activation of JAK kinases, as well as the phosphorylation and activation of transcription activators STAT3, STAT5, and STAT6. Studies of the mouse counterpart suggested that this cytokine may increase the expression of apoptosis inhibitor BCL2L1/BCL-x(L), possibly through the transcription activation activity of STAT6, and thus prevent apoptosis. Alternatively spliced transcript variants of this gene have been reported. [provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~97.4 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 IL15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000585.5. 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 | 1 | 1 | 3 | ||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 18 | 1 | 1 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000576.1 | 6 | MANE Select | |
| Ensembl | ENSP00000323505.4 | 6 | MANE Select | |
| RefSeq | NP_751915.1 | 5 | Standard | |
| Ensembl | ENSP00000296545.7 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Jak-STAT signaling pathway - Homo sapiens (human)
- TNF signaling pathway - Homo sapiens (human)
- HTLV-I infection - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Rheumatoid arthritis - Homo sapiens (human)
Biological Process
- natural killer cell differentiation
- NK T cell proliferation
- inflammatory response
- immune response
- signal transduction
Molecular Function
- cytokine activity
- cytokine receptor binding
- protein binding
Cellular Component
- extracellular region
- extracellular space
- nucleoplasm
- cytoplasm
- endosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296545
- Coding exons
- 6
- Length
- 97389
- Individuals with no LoFs
- 106645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 106646
- p
- 0.00000469
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0747 | 79 | 80.9 | 0.977 | 0.00000364 | 1086 |
| Missense (PolyPhen) | 24 | 27.638 | 0.86836 | 407 | ||
| Synonymous | 1.08 | 20 | 27.1 | 0.737 | 0.00000132 | 275 |
| Loss of Function | 2.36 | 1 | 8.36 | 0.120 | 4.40e-7 | 103 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000048 | 0.000048 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytokine that stimulates the proliferation of T- lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha.;
Recessive Scores
- pRec
- 0.595
Intolerance Scores
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 62.74
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.454
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |