The clinical relevance of WDFY4 in autoimmune diseases in diverse ancestral populations.

ABSTRACT

WD repeat- and FYVE domain-containing protein 4 (WDFY4), coded by a gene on 10q11.23, is a member of the BEACH (Beige and Chediak-Higashi) domain-containing family. Genome-wide association studies identified WDFY4 variants as a risk factor for SLE in Asian and European populations. WDFY4 variants are also associated with RA and primary biliary cholangitis, in different ancestry populations. The WDFY4 protein plays an essential role in the cross-presentation of classic dendritic cells, reactive oxygen species-induced apoptosis of CD8+ T cells, and non-canonical autophagic activity in B cells. A novel variant rs7919656 was identified in Japanese clinically amyopathic dermatomyositis patients, with a highly expressed truncated isoform augmenting the melanoma differentiation-associated gene 5 (MDA5) signalling pathway. The same variant was later found to be significantly associated with RP-ILD in Chinese MDA5+DM patients. Here, we briefly review the association of WDFY4 with autoimmune diseases and its known function in immune response.