IL2
protein-codinginterleukin 2, the group of Interleukins
Gene summary
This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli. [provided by RefSeq, Sep 2020]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.3 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 IL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000586.4. 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 | 0 | |||||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 0 | 1 | 0 | 3 |
Highest pathogenic variant AF is 0.0000014001131
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000577.2 | 4 | MANE Select | |
| Ensembl | ENSP00000226730.5 | 4 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Type I diabetes mellitus - Homo sapiens (human)
- T cell receptor signaling pathway - Homo sapiens (human)
- Allograft rejection - Homo sapiens (human)
- Graft-versus-host disease - Homo sapiens (human)
Biological Process
- MAPK cascade
- negative regulation of protein phosphorylation
- adaptive immune response
- leukocyte activation involved in immune response
- negative regulation of B cell apoptotic process
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- cytokine activity
- interleukin-2 receptor binding
- protein binding
- growth factor activity
Cellular Component
- extracellular region
- extracellular space
- cell
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000226730
- Coding exons
- 4
- Length
- 5256
- Individuals with no LoFs
- 123887
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123888
- p
- 0.00000404
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.43 | 38 | 72.2 | 0.526 | 0.00000312 | 1002 |
| Missense (PolyPhen) | 11 | 18.771 | 0.586 | 271 | ||
| Synonymous | -1.14 | 34 | 26.6 | 1.28 | 0.00000121 | 286 |
| Loss of Function | 1.86 | 1 | 5.85 | 0.171 | 2.46e-7 | 79 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine- activated killer cells, natural killer cells, and glioma cells.;
- Disease
- DISEASE: Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17. {ECO:0000269|PubMed:1396583}.;
Recessive Scores
- pRec
- 0.956
Intolerance Scores
- RVIS EVS
- 0.3
- RVIS percentile EVS
- 71.81
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.833
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |