GLIS3 encodes a transcription factor belonging to the Kruppel-like zinc finger protein family. The GLIS3 nuclear protein has five C2H2-type zinc finger domains and functions as both an activator and repressor of transcription, thus playing a key regulatory role in development. GLIS3 is expressed in several tissues of the body but is most highly expressed in islet beta cells. It is found to be associated with pancreatic endocrine development, beta-cell maintenance and insulin regulation.
GLIS3 expression occurs early in embryogenesis and thus it is easy to see how defects in the gene can have severe pathological consequences. Mutations in the GLIS3 gene are associated with NDH syndrome, a congenital disorder characterized by intrauterine growth retardation, non-immune neonatal diabetes mellitus, congenital hypothyroidism and facial dysmorphism. Genome wide association studies have also identified GLIS3 as a risk locus for Type-1 and Type-2 Diabetes.