Innate immunity activator protein (INAVA) (INAVA)

Innate immunity activator protein (INAVA), also known as C1orf106, is a scaffold protein that plays a dual role in human health, primarily by maintaining the integrity of the intestinal epithelial barrier and modulating innate immune signaling (UniProt Q3KP66; Science, 2018). In the gut, INAVA localizes to apical junctional complexes where it interacts with cytohesins and the SCF ubiquitin ligase complex to stabilize adherens junctions and prevent the internalization of E-cadherin (Science, 2018; JCI, 2017). Genetic variants in the INAVA gene, such as the rs7554511 risk allele and the 333F missense mutation, are strongly linked to inflammatory bowel disease (IBD) because they lead to reduced protein expression or stability (Science, 2018). This deficiency results in a "leaky gut" phenotype and impaired clearance of intestinal pathogens, contributing to chronic inflammation in Crohn's disease and ulcerative colitis (JCI, 2017; Science, 2018). Conversely, in oncology, INAVA is identified as a TGF-beta target gene that is frequently overexpressed in breast and ovarian cancers (Cells, 2024; Frontiers in Cell and Developmental Biology, 2022). In these contexts, it promotes tumor cell self-renewal, migration, and metastasis by modulating transcription factors like ELF5 and GATA3 (Cells, 2024). While no direct therapeutic agents are currently approved for clinical use, INAVA is an active area of research for developing therapies that restore the epithelial barrier in IBD or inhibit its pro-tumorigenic functions in cancer (Science, 2018; Cells, 2024). Therapeutic strategies being explored include small molecules that stabilize the protein in IBD or inhibitors that block its induction in metastatic disease (Science, 2018; Cells, 2024).

Other names

C1orf106Chromosome 1 open reading frame 106FLJ10901MGC125608

Restoration of epithelial barrier integrity through stabilization of adherens junctions and enhancement of pattern recognition receptor (PRR)-induced innate immune signaling.