Systematic and proactive evaluation of AIRE missense variant effects.

Pathogenic variants in the autoimmune regulator (autoimmune regulator) cause autoimmune polyendocrine syndrome type 1 (APS-1), a rare primary immunodeficiency disease with symptoms including hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidiasis.

Earlier diagnoses can benefit those with APS-1, and APS-1 diagnosis by autoimmune regulator sequencing is increasingly common.

Here, we used an insulin-promoter-driven reporter to proactively assess the function of 9,790 autoimmune regulator missense variants.