IFNLR1 gene

The IFNLR1 gene (IFNLR1 stands for: Interferon Lambda Receptor 1) is a protein-coding gene located on chromosome 1p36.11. An important paralog of this gene is IL20RA.

The protein encoded by this gene belongs to the class II cytokine receptor family. This protein forms a receptor complex with the interleukin-10 receptor, beta (IL10RB). The receptor complex has been shown to interact with three closely related cytokines, including interleukin 28A (IL28A), interleukin-28B (IL28B) and interleukin-29 (IL29). The expression of all three cytokines can be induced by viral infection (Zhang AM et al. 2020). In cells overexpressing this protein, an enhanced response to interleukin-28A and interleukin-29 (syn: interferon-lambda) but a reduced response to interleukin-28B was observed. Three alternatively spliced transcript variants encoding different isoforms are known.

Diseases associated with IFNLR1 include

• Hypotrichosis, congenital, with juvenile macular dystrophy (OMIM: OMIM: 601553), a disorder characterized by early hair loss and severe degenerative changes in the macula of the retina, leading to blindness in the second to third decade of life. It is caused by an autosomal recessive mutation of the CDH3 gene on chromosome 16q22.1.8 genes associated with hypotrichosis, congenital, with juvenile macular dystrophy 2 with high evidence (elite gene associations) and 6 non-elite and textminated gene associations. These include: the IFNLR1 gene, the IFNL2 gene and the IL26 gene.

and

• the neurofibromatosis Noonan syndrome (Watson syndrome). This autosomal dominant inherited syndrome (OMIM: 193520) is a systemic disease characterized by pulmonary stenosis, cafe-au-lait spots, reduced intellectual abilities, short stature, relative macrocephaly, Lisch nodules and neurofibromas. It is considered an atypical form of neurofibromatosis and is allelic to NF1 as it has the same gene association. Of 19 genes associated with Watson syndrome, 3 show high evidence (elite gene associations) and 16 show non-elite and text-mined gene associations including IFNLR1.

1. Goel RR et al. (2020) Interferon lambda promotes immune dysregulation and tissue inflammation in TLR7-induced lupus. Proc Natl Acad Sci U S A 117:5409-5419.
2. Watson GH (1967) Pulmonary stenosis, cafe-au-lait spots, and dull intelligence. Arch Dis Child 42: 303-307.
3. Zhang AM et al. (2020) Genetic Polymorphisms of the IFNLR1 Gene Correlate with HCV Infection and Biochemical Features of Chronic HCV Patients in Yunnan, China. Immunol Invest 49:453-461