IFNL3
protein-codinginterferon lambda 3, the group of Interferons
Gene summary
This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA). [provided by RefSeq, Jul 2008]
- IL28B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Variants may have pharmacogenomic importance, as selection and dosing of medications (including peg-interferon and ribavirin) may be affected by the presence of variants
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IFNL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_172139.4. 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 | 3 | 3 | ||||
| missense | 39 | 1 | 6 | 46 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 39 | 4 | 6 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_742151.2 | 5 | MANE Select | |
| Ensembl | ENSP00000409000.2 | 5 | MANE Select | |
| RefSeq | NP_001333866.1 | 6 | Standard | |
| Ensembl | ENSP00000481633.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Jak-STAT signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- JAK-STAT-Core
- Type III interferon signaling
Biological Process
- JAK-STAT cascade
- regulation of signaling receptor activity
- cytokine-mediated signaling pathway
- negative regulation of viral genome replication
- innate immune response
Molecular Function
- signaling receptor binding
- cytokine activity
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000413851
- Coding exons
- 5
- Length
- 1401
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125731
- p
- 0.0000597
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.16 | 158 | 122 | 1.30 | 0.00000758 | 1230 |
| Missense (PolyPhen) | 23 | 24.97 | 0.92111 | 328 | ||
| Synonymous | -0.453 | 60 | 55.7 | 1.08 | 0.00000347 | 436 |
| Loss of Function | -1.01 | 10 | 7.09 | 1.41 | 3.01e-7 | 83 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN- stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type- selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression. {ECO:0000269|PubMed:12469119, ECO:0000269|PubMed:12483210}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- RVIS EVS
- 1.28
- RVIS percentile EVS
- 93.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |