IFIT5 Gene - Structure, Function, and Clinical Significance

IFIT5 (Interferon Induced Protein with Tetratricopeptide Repeats 5) is a protein-coding gene located on chromosome 10q23.31. It encodes a member of the interferon-induced protein with tetratricopeptide repeats (IFIT) family, which plays a critical role in innate immunity by recognizing and binding viral RNA, particularly 5'-triphosphate RNA, thereby inhibiting viral replication and translation. IFIT5 is induced by type I interferons and is involved in antiviral defense against RNA viruses such as influenza A virus and vesicular stomatitis virus. It also modulates RIG-I signaling and interacts with other IFIT family members to form complexes that sequester viral RNA.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RIG-I-like receptor signaling pathway (KEGG: hsa04622)

• Interferon alpha/beta signaling (Reactome: R-HSA-909733)

• Antiviral mechanism by IFN-stimulated genes (Reactome: R-HSA-1169410)

• Innate Immune System (Reactome: R-HSA-168249)

The IFIT5 protein (UniProt Q13325) is a 482-amino acid member of the IFIT family, characterized by multiple tetratricopeptide repeats (TPRs) that mediate protein-protein and protein-RNA interactions. It is predominantly cytoplasmic and is rapidly induced upon interferon stimulation. IFIT5 specifically recognizes 5'-triphosphate moieties on viral RNA, a molecular signature absent from most host RNAs, allowing selective targeting of viral genomes. This binding inhibits viral translation and replication. IFIT5 also interacts with other IFIT proteins (e.g., IFIT1, IFIT2) to form complexes that sequester viral RNA and modulate RIG-I signaling. Its expression is tightly regulated, and dysregulation is implicated in autoimmune diseases and certain cancers.